Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis.

Mechanotransduction is a key determinant of tissue homeostasis and tumor progression. It is driven by intercellular adhesions, cell contractility, and forces generated within the microenvironment and is dependent on extracellular matrix composition, organization, and compliance. We show that caveolin-1 (Cav1) favors cell elongation in three-dimensional cultures and promotes Rho- and force-dependent contraction, matrix alignment, and microenvironment stiffening through regulation of p190RhoGAP. In turn, microenvironment remodeling by Cav1 fibroblasts forces cell elongation. Cav1-deficient mice have disorganized stromal tissue architecture. Stroma associated with human carcinomas and melanoma metastases is enriched in Cav1-expressing carcinoma-associated fibroblasts (CAFs). Cav1 expression in breast CAFs correlates with low survival, and Cav1 depletion in CAFs decreases CAF contractility. Consistently, fibroblast expression of Cav1, through p190RhoGAP regulation, favors directional migration and invasiveness of carcinoma cells in vitro. In vivo, stromal Cav1 remodels peri- and intratumoral microenvironments to facilitate tumor invasion, correlating with increased metastatic potency. Thus, Cav1 modulates tissue responses through force-dependent architectural regulation of the microenvironment.

Formyl peptide receptor 2 and heart disease.

Formyl peptide receptor type 2 (FPR2) regulates the initiation and resolution phases of the inflammatory response. In the setting of heart injury and disease, dysregulated inflammation can potentiate maladaptive healing and pathological remodeling of the heart leading to cardiac dysfunction and failure. The potential to regulate and resolve adverse inflammation is postulated to improve outcome in the setting of heart disease. This review covers emerging concepts on the role of FPR2 in heart disease and strategies to activate pro-resolution processes to limit disease progression. We summarize key preclinical studies that support use of FPR2 agonists in heart disease. Finally, we briefly discuss the status of FPR2 agonists under evaluation in the clinic.

G3BP1-dependent mechanism suppressing protein aggregation in Huntington's models and its demise upon stress granule assembly.

Stress granules are membrane-less ribonucleoprotein organelles that assemble upon exposure to stress conditions, but rapidly disassemble upon removal of stress. However, chronic stress can lead to persistent stress granules, a feature of distinct age-related neurodegenerative disorders. Among them, Huntington's disease (HD), which is caused by mutant expansion of the polyglutamine (polyQ) repeats of huntingtin protein (HTT), leading to its aggregation. To identify modulators of mutant HTT aggregation, we define its interactome in striatal neurons differentiated from patient-derived induced pluripotent stem cells (HD-iPSCs). We find that HTT interacts with G3BP1, a characteristic component of stress granules. Knockdown of G3BP1 increases mutant HTT protein levels and abolishes the ability of iPSCs as well as their differentiated neural counterparts to suppress mutant HTT aggregation. Moreover, loss of G3BP1 hastens polyQ-expanded aggregation and toxicity in the neurons of HD C. elegans models. Likewise, the assembly of G3BP1 into stress granules upon distinct stress conditions also reduces its interaction with HTT in human cells, promoting mutant HTT aggregation. Notably, enhancing the levels of G3BP1 is sufficient to induce proteasomal degradation of mutant HTT and prevent its aggregation, whereas the formation of stress granules blocks these ameliorative effects. In contrast, a mutant G3BP1 variant that cannot accumulate into granules retains its capacity to prevent mutant HTT aggregation even when the cells assemble stress granules. Thus, our findings indicate a direct role of G3BP1 and stress granule assembly in mutant HTT aggregation that may have implications for HD.

Nanorheology and Nanoindentation Revealed a Softening and an Increased Viscous Fluidity of Adherent Mammalian Cells upon Increasing the Frequency.

The nanomechanical response of a cell depends on the frequency at which the cell is probed. The components of the cell that contribute to this property and their interplay are not well understood. Here, two force microscopy methods are integrated to characterize the frequency and/or the velocity-dependent properties of living cells. It is shown on HeLa and fibroblasts, that cells soften and fluidize upon increasing the frequency or the velocity of the deformation. This property was independent of the type and values (25 or 1000 nm) of the deformation. At low frequencies (2-10 Hz) or velocities (1-10 µm s-1 ), the response is dominated by the mechanical properties of the cell surface. At higher frequencies (>10 Hz) or velocities (>10 µm s-1 ), the response is dominated by the hydrodynamic drag of the cytosol. Softening and fluidization does not seem to involve any structural remodeling. It reflects a redistribution of the applied stress between the solid and liquid-like elements of the cell as the frequency or the velocity is changed. The data indicates that the quasistatic mechanical properties of a cell featuring a cytoskeleton pathology might be mimicked by the response of a non-pathological cell which is probed at a high frequency.

On the relevance of query definition in the performance of 3D ligand-based virtual screening.

Ligand-based virtual screening (LBVS) methods are widely used to explore the vast chemical space in the search of novel compounds resorting to a variety of properties encoded in 1D, 2D or 3D descriptors. The success of 3D-LBVS is affected by the overlay of molecular pairs, thus making selection of the template compound, search of accessible conformational space and choice of the query conformation to be potential factors that modulate the successful retrieval of actives. This study examines the impact of adopting different choices for the query conformation of the template, paying also attention to the influence exerted by the structural similarity between templates and actives. The analysis is performed using PharmScreen, a 3D LBVS tool that relies on similarity measurements of the hydrophobic/philic pattern of molecules, and Phase Shape, which is based on the alignment of atom triplets followed by refinement of the volume overlap. The study is performed for the original DUD-E+ database and a Morgan Fingerprint filtered version (denoted DUD-E+-Diverse; available in https://github.com/Pharmacelera/Query-models-to-3DLBVS ), which was prepared to minimize the 2D resemblance between template and actives. Although in most cases the query conformation exhibits a mild influence on the overall performance, a critical analysis is made to disclose factors, such as the content of structural features between template and actives and the induction of conformational strain in the template, that underlie the drastic impact of the query definition in the recovery of actives for certain targets. The findings of this research also provide valuable guidance for assisting the selection of the query definition in 3D LBVS campaigns.

Interfacial water on collagen nanoribbons by 3D AFM.

Collagen is the most abundant structural protein in mammals. Type I collagen in its fibril form has a characteristic pattern structure that alternates two regions called gap and overlap. The structure and properties of collagens are highly dependent on the water and mineral content of the environment. Here, we apply 3D AFM to characterize at angstrom-scale resolution the interfacial water structure of collagen nanoribbons. For a neutral tip, the interfacial water structure is characterized by the oscillation of the water particle density distribution with a value of 0.3 nm (hydration layers). The interfacial structure does not depend on the collagen region. For a negatively charged tip, the interfacial structure might depend on the collagen region. Hydration layers are observed in overlap regions, while in gap regions, the interfacial solvent structure is dominated by electrostatic interactions. These interactions generate interlayer distances of 0.2 nm.

Generalized anosognosia, anosodiaphoria, and visual hallucinations with bilateral enucleation after severe bifrontal brain injury: a case report describing similarities with and differences from Anton syndrome.

Visual anosognosia, associated with confabulations and cortical blindness in the context of occipital lobe injury, is known as Anton syndrome. Patients with this syndrome strongly deny their vision loss and confabulate to compensate for both visual loss and memory impairments. In this article, we present a case of a patient with some similarities to Anton syndrome, however, with several differences in clinical presentation. Bifrontal brain injury, bilateral enucleation, affective indifference (anosodiaphoria), generalized anosognosia, and the conviction that vision will resume mark clear clinical differences with Anton syndrome. Differentiating these findings from Anton syndrome will help occupational therapists, neuropsychologists, speech-language pathologists, physical therapists, and physicians when assessing frontal lobe brain injury with total and partial visual loss. This case demonstrates that visual anosognosia and confabulations can occur without occipital lobe dysfunction or cortical blindness.

Dual-Mode Solidly Mounted Resonator-Based Sensor for Temperature and Humidity Detection and Discrimination.

Sensors based on solidly mounted resonators (SMRs) exhibit a good set of properties, such as high sensitivity, fast response, low resolution limit and low production cost, which makes them an appealing technology for sensing applications. However, they can suffer from cross-sensitivity issues, as their response can be altered by undesirable ambient factors, such as temperature and humidity variations. In this work we propose a method to discriminate humidity variations from the general frequency response using an SMR specifically manufactured to operate in a dual-mode (displaying two close resonances). The two modes behave similarly towards humidity changes (-1.94 kHZ/(%RH)) for resonance one and -1.62 kHZ/(%RH) for resonance two), whereas their performance under temperature changes is significantly different, displaying 2.64 kHZ/°C for resonance one and 34.21 kHZ/°C for resonance two. This allows for the decoupling process to be carried out in a straightforward manner. Frequency response is tracked under different humidity conditions, in the -20 °C to room temperature region, proving that this behavior is reproducible in any given environment.

Obtention and Characterization of Microcrystalline Cellulose from Industrial Melon Residues Following a Biorefinery Approach.

Residual melon by-products were explored for the first time as a bioresource of microcrystalline cellulose (MCC) obtention. Two alkaline extraction methods were employed, the traditional (4.5% NaOH, 2 h, 80 °C) and a thermo-alkaline in the autoclave (2% NaOH, 1 h, 100 °C), obtaining a yield of MCC ranging from 4.76 to 9.15% and 2.32 to 3.29%, respectively. The final MCCs were characterized for their chemical groups by Fourier-transform infrared spectroscopy (FTIR), crystallinity with X-ray diffraction, and morphology analyzed by scanning electron microscope (SEM). FTIR spectra showed that the traditional protocol allows for a more effective hemicellulose and lignin removal from the melon residues than the thermo-alkaline process. The degree of crystallinity of MCC ranged from 51.51 to 61.94% and 54.80 to 55.07% for the thermo-alkaline and traditional processes, respectively. The peaks detected in X-ray diffraction patterns indicated the presence of Type I cellulose. SEM analysis revealed microcrystals with rough surfaces and great porosity, which could remark their high-water absorption capacity and drug-carrier capacities. Thus, these findings could respond to the need to valorize industrial melon by-products as raw materials for MCC obtention with potential applications as biodegradable materials.

Laparoscopic onlay-flap ureteroplasty using cecal appendix.

INTRODUCTION: The management of ureteral strictures longer than 1-2 cm must be treated by major surgery (1, 2). The strictures located at the distal part of the ureter can be managed by a ureteral reimplantation using a psoas hitch or a Boari flap depending on its proximity to the bladder (3). Those located at the proximal ureter can be treated by a pyeloplasty (4). The ureteric strictures in the mid-ureter are the ones that pose a greater challenge for the urologist because a ureteral substitution is needed, either using a segment of the intestine or a buccal mucosa graft (5, 6). Our main objective is to present the management and results at 36 months of a patient with a right mid-ureter stricture. MATERIAL AND METHODS: A 63-year-old male with chronic kidney disease (CKD) and a right single functioning kidney was referred to our department with the diagnosis of a 3 cm stricture in the right mid-ureter. He had a long-term JJ-stent in place but in the last year we had to replace it three times precociously and he even needed the placement of a nephrostomy tube due to the obstruction of the JJ-stent. Accordingly, a permanent resolution was sought and a laparoscopic onlay-flap ureteroplasty using cecal appendix was performed. RESULTS: The first step was to identify the cecal appendix. Then we identified and dissected the ureter. With the ureter dissected, we performed a ureteroscopy to pinpoint the stricture. Once we knew where the stricture was, we proceeded with the ureterotomy and preparation of the cecal appendix. The final step was to perform the ureteroplasty between the ureter and the cecal appendix placing a JJ-stent before the last stitches were done. Total operative time was 190 minutes without any intraoperative complication. The JJ-stent was removed 7 weeks later. The follow-up of the patient was done with regular blood test and ultrasound to rule out deterioration of the CKD and worsening of the residual hydronephrosis. With a follow-up of 36 months, the patient is stent free, he hasn't had any further intervention and neither the CKD nor the hydronephrosis haven't worsened. CONCLUSIONS: Laparoscopic onlay-flap ureteroplasty using cecal appendix is a feasible and well tolerated procedure for patients with right mid-ureter stricture. However, we must bear in mind the difficulty of these cases and they should be performed in expert centers.

Physical activity and its relationship to burden and health concerns in family caregivers of people with dementia.

BACKGROUND: Caring for people with dementia (PwD) usually triggers stress and leads to mental and somatic health complaints (SHCs). Physical activity (PA) can provide burden relief in PwD caregivers, but it is not clear whether PA habits would contribute to reducing SHCs. This study aims to analyze the effect of PA on the relationship between burden and SHCs in a sample of family caregivers of PwD. METHODS: One hundred and fifty-seven caregivers of PwD reported their PA habits, and completed the Giessen's Subjective Health Complaints Questionnaire (GBB-8) and the Zarit Burden Interview (ZBI). The relationship between PA habits, burden of care (ZBI), and SHCs (B-GBB-8 scale) was examined. Subsequently, the moderating effect of PA habits on the relationship between burden and SHCs was tested. RESULTS: PA habit was inversely associated with ZBI (rbp = -0.242) and GBB-8 scores (rbp (Gastrointestinal) = -0.174; rbp (Musculoskeletal) = -0.195; rbp (Exhaustion) = -0.247; rbp (Cardiovascular) = -0.250; and rbp (Overall) = -0.257, respectively), whereas moderate positive correlations were found between ZBI and GBB-8 scores (r (Gastrointestinal) = 0.483; r (Musculoskeletal) = 0.536; r (Exhaustion) = 0.542; r (Cardiovascular) = 0.438; and r (Overall) = 0.598, respectively). The interaction effect of PA habit and burden was significant for the overall SHCs (b = -0.11; P < 0.05) and cardiovascular complaints (b = -0.06; P < 0.05). However, the association between burden and SHCs was significant (P < 0.001) only for sedentary caregivers. CONCLUSION: These findings indicate that maintaining an active lifestyle through regular PA could potentially help alleviate the adverse effects of caregiver burden on somatic health among caregivers of PwD. Encouraging and endorsing PA interventions for informal caregivers might yield substantial advantages for their health and general well-being.

Stenting performs better than drug-coated balloon angioplasty in popliteal lesions.

BACKGROUND: Peripheral arterial disease (PAD) is a common and highly morbid disease. Although there have been recent advancements in the endovascular modalities to treat PAD, comparisons of these strategies, especially in the popliteal region, remain underinvestigated. The objective of this study was to compare midterm outcomes in patients with PAD undergoing treatment with both novel and SS compared with drug-coated balloon (DCB) angioplasty. METHODS: All patients at a multi-institution health system treated for PAD in the popliteal region from 2011 to 2019 were identified. Presenting features, operative details, and outcomes were included in the analysis. Patients who underwent popliteal revascularization with stents were compared with DCB. SS were compared separately with novel dedicated stents. Two-year primary patency was the primary outcome. RESULTS: We included 408 patients (72.7 ± 11.8 years old; 57.1% men) in the analysis. There were 221 (54.7%) patients who underwent popliteal stenting and 187 (45.3%) who underwent popliteal DCB. There were high rates of tissue loss in both groups (57.9% vs 50.8%; P = .14). Stented patients had longer lesions (112.4 ± 3.2 vs 100.2 ± 5.8 mm; P = .03) and higher rates of concomitant superficial femoral artery treatment (88.2% vs 39.6%; P < .01). Chronic total occlusions accounted for the majority of lesions treated (stent 62.4%, DCB 64.2%). Perioperative complications were similar between groups. Primary patency for the stented group was higher at two years than the DCB group (61.0% vs 46.1%; P = .03). When evaluating stented patients only, SS had higher 2-year patency than novel stents in the popliteal segment (69.6% vs 51.4%; P = .04). On multivariable analysis, stenosis, as opposed to chronic total occlusion, was associated with improved patency (hazard ratio, 0.49; 95% confidence interval, 0.25-0.96; P = .04), whereas novel stents were associated with worse primary patency (hazard ratio, 2.01; 95% confidence interval, 1.09-3.73; P = .03). CONCLUSIONS: In a population of patients with severe vascular disease, stents do not have inferior patency and limb salvage rates compared with DCB angioplasty when treating the popliteal region. For patients with advanced vascular disease, and especially tissue loss, stents and DCB are both beneficial when treating popliteal lesions.

Eco-evolutionary significance of "loners".

Loners-individuals out of sync with a coordinated majority-occur frequently in nature. Are loners incidental byproducts of large-scale coordination attempts, or are they part of a mosaic of life-history strategies? Here, we provide empirical evidence of naturally occurring heritable variation in loner behavior in the model social amoeba Dictyostelium discoideum. We propose that Dictyostelium loners-cells that do not join the multicellular life stage-arise from a dynamic population-partitioning process, the result of each cell making a stochastic, signal-based decision. We find evidence that this imperfectly synchronized multicellular development is affected by both abiotic (environmental porosity) and biotic (signaling) factors. Finally, we predict theoretically that when a pair of strains differing in their partitioning behavior coaggregate, cross-signaling impacts slime-mold diversity across spatiotemporal scales. Our findings suggest that loners could be critical to understanding collective and social behaviors, multicellular development, and ecological dynamics in D. discoideum. More broadly, across taxa, imperfect coordination of collective behaviors might be adaptive by enabling diversification of life-history strategies.

Insights and guidelines to interpret forces and deformations at the nanoscale by using a tapping mode AFM simulator: dForce 2.0.

Amplitude modulation (tapping mode) AFM is the most versatile AFM mode for imaging surfaces at the nanoscale in air and liquid environments. However, it remains challenging to estimate the forces and deformations exerted by the tip. We introduce a new simulator environment to predict the values of the observables in tapping mode AFM experiments. The relevant feature of dForce 2.0 is the incorporation of contact mechanics models aimed to describe the properties of ultrathin samples. These models were essential to determine the forces applied on samples such as proteins, self-assembled monolayers, lipid bilayers, and few-layered materials. The simulator incorporates two types of long-range magnetic forces. The simulator is written in an open-source code (Python) and it can be run from a personal computer.

Long-term outcomes in COVID-19 patients admitted to intensive care in Denmark: A nationwide observational study.

BACKGROUND: Among ICU patients with COVID-19, it is largely unknown how the overall outcome and resource use have changed with time, different genetic variants, and vaccination status. METHODS: For all Danish ICU patients with COVID-19 from March 10, 2020 to March 31, 2022, we manually retrieved data on demographics, comorbidities, vaccination status, use of life support, length of stay, and vital status from medical records. We compared patients based on the period of admittance and vaccination status and described changes in epidemiology related to the Omicron variant. RESULTS: Among all 2167 ICU patients with COVID-19, 327 were admitted during the first (March 10-19, 2020), 1053 during the second (May 20, 2020 to June 30, 2021) and 787 during the third wave (July 1, 2021 to March 31, 2022). We observed changes over the three waves in age (median 72 vs. 68 vs. 65 years), use of invasive mechanical ventilation (81% vs. 58% vs. 51%), renal replacement therapy (26% vs. 13% vs. 12%), extracorporeal membrane oxygenation (7% vs. 3% vs. 2%), duration of invasive mechanical ventilation (median 13 vs. 13 vs. 9 days) and ICU length of stay (median 13 vs. 10 vs. 7 days). Despite these changes, 90-day mortality remained constant (36% vs. 35% vs. 33%). Vaccination rates among ICU patients were 42% as compared to 80% in society. Unvaccinated versus vaccinated patients were younger (median 57 vs. 73 years), had less comorbidity (50% vs. 78%), and had lower 90-day mortality (29% vs. 51%). Patient characteristics changed significantly after the Omicron variant became dominant including a decrease in the use of COVID-specific pharmacological agents from 95% to 69%. CONCLUSIONS: In Danish ICUs, the use of life support declined, while mortality seemed unchanged throughout the three waves of COVID-19. Vaccination rates were lower among ICU patients than in society, but the selected group of vaccinated patients admitted to the ICU still had very severe disease courses. When the Omicron variant became dominant a lower fraction of SARS-CoV-2 positive patients received COVID treatment indicating other causes for ICU admission.

Real-Time Wavefront Sensing at High Resolution with an Electrically Tunable Lens.

We have designed, assembled, and evaluated a compact instrument capable of capturing the wavefront phase in real time, across various scenarios. Our approach simplifies the optical setup and configuration, which reduces the conventional capture and computation time when compared to other methods that use two defocused images. We evaluated the feasibility of using an electrically tunable lens in our camera by addressing its issues and optimizing its performance. Additionally, we conducted a comparison study between our approach and a Shack-Hartmann sensor. The camera was tested on multiple targets, such as deformable mirrors, lenses with aberrations, and a liquid lens in movement. Working at the highest resolution of the CMOS sensor with a small effective pixel size enables us to achieve the maximum level of detail in lateral resolution, leading to increased sensitivity to high-spatial-frequency signals.

Characterizing SOD1 mutations in Spain. The impact of genotype, age, and sex in the natural history of the disease.

INTRODUCTION: The aim of this study is to describe the frequency and distribution of SOD1 mutations in Spain, and to explore those factors contributing to their phenotype and prognosis. METHODS: Seventeen centres shared data on amyotrophic lateral sclerosis (ALS) patients carrying pathogenic or likely pathogenic SOD1 variants. Multivariable models were used to explore prognostic modifiers. RESULTS: In 144 patients (from 88 families), 29 mutations (26 missense, 2 deletion/insertion and 1 frameshift) were found in all 5 exons of SOD1, including 7 novel mutations. 2.6% of ALS patients (including 17.7% familial and 1.3% sporadic) were estimated to carry SOD1 mutations. Its frequency varied considerably between regions, due to founder events. The most frequent mutation was p.Gly38Arg (n = 58), followed by p.Glu22Gly (n = 11), p.Asn140His (n = 10), and the novel p.Leu120Val (n = 10). Most mutations were characterized by a protracted course, and some of them by atypical phenotypes. Older age of onset was independently associated with faster disease progression (exp(Estimate) = 1.03 [0.01, 0.05], p = 0.001) and poorer survival (HR = 1.05 [1.01, 1.08], p = 0.007), regardless of the underlying mutation. Female sex was independently associated to faster disease progression (exp(Estimate) = 2.1 [1.23, 3.65], p = 0.012) in patients carrying the p.Gly38Arg mutation, resulting in shorter survival compared with male carriers (236 vs 301 months). CONCLUSIONS: These data may help to evaluate the efficacy of SOD1 targeted treatments, and to expand the number of patients that might benefit from these treatments.

A comparison of modelled serum cTnT and cTnI kinetics after 60 min swimming.

Post-exercise elevations of cardiac troponin T (cTnT) and I (cTnI) are often used in isolation but interpreted interchangeably. Research suggests, however, that post-exercise cTn kinetic might differ with each isoform. In this cross-sectional observational study, we collected blood samples before, immediately after (5 minutes), and at 1-, 3-, 6-, 12-, and 24-hour post-exercise in a mixed cohort of 56 participants after a distance-trial of 60 min continuous swimming (age range from 14 to 22, 57.1% female). Cardiac troponin kinetics were modelled using Bayesian mixed-effects models to estimate time to peak (TTP) and peak concentration (PC) for each isoform, while controlling for participants sex, tanner stage and average relative heart rate during the test. Exercise induced an elevation of cTnT and cTnI in 93% and 75% of the participants, respectively. Cardiac troponin T peaked earlier, at 2.9 h (CI: 2.6 - 3.2 h) post-exercise, whereas cTnI peaked later, at 4.5 h (CI: 4.2 - 4.9 h). Peak concentrations for cTnT and cTnI were 2.5 ng/L, CI: 0 - 11.2 ng/L and 2.16 ng/L, CI: 0 - 22.7 ng/L, respectively. Additionally, we did not observe a systematic effect of sex and maturational status mediating cTn responses.

Long-term cognitive and functional status in Danish ICU patients with COVID-19.

BACKGROUND: ICU admission due to COVID-19 may result in cognitive and physical impairment. We investigated the long-term cognitive and physical status of Danish ICU patients with COVID-19. METHODS: We included all patients with COVID-19 admitted to Danish ICUs between March 10 and May 19, 2020. Patients were the contacted prospectively at 6 and 12 months for follow-up. Our primary outcomes were cognitive function and frailty at 6 and 12 months after ICU admission, estimated by the Mini Montreal Cognitive Assessment, and the Clinical Frailty Scale. Secondary outcomes were 6- and 12-month mortality, health-related quality of life (HRQoL) assessed by EQ-5D-5L, functional status (Barthel activities of daily living and Lawton-Brody instrumental activities of daily living), and fatigue (Fatigue Assessment Scale). The study had no information on pre-ICU admission status for the participants. RESULTS: A total of 326 patients were included. The 6- and 12-month mortality was 37% and 38%, respectively. Among the 204 six-month survivors, 105 (51%) participated in the 6-month follow-up; among the 202 twelve-month survivors, 95 (47%) participated in the 12-month follow-up. At 6 months, cognitive scores indicated impairment for 26% (95% confidence interval [CI], 11.4-12.4) and at 12 months for 17% (95% CI, 12.0-12.8) of participants. Frailty was indicated in 20% (95% CI, 3.4-3.9) at 6 months, and for 18% (95% CI, 3.3-3.8) at 12 months. Fatigue was reported by 52% at 6 months, and by 47% at 12 months. For HRQoL, moderate, severe, or extreme health problems were reported by 28% at 6 months, and by 25% at 12 months. CONCLUSION: Long-term cognitive, functional impairment was found in up to one in four of patients surviving intensive care for COVID-19. Fatigue was present in nearly half the survivors at both 6 and 12 months. However, pre-ICU admission status of the patients was unknown.

Changes over time in characteristics, resource use and outcomes among ICU patients with COVID-19-A nationwide, observational study in Denmark.

BACKGROUND: Characteristics and care of intensive care unit (ICU) patients with COVID-19 may have changed during the pandemic, but longitudinal data assessing this are limited. We compared patients with COVID-19 admitted to Danish ICUs in the first wave with those admitted later. METHODS: Among all Danish ICU patients with COVID-19, we compared demographics, chronic comorbidities, use of organ support, length of stay and vital status of those admitted 10 March to 19 May 2020 (first wave) versus 20 May 2020 to 30 June 2021. We analysed risk factors for death by adjusted logistic regression analysis. RESULTS: Among all hospitalised patients with COVID-19, a lower proportion was admitted to ICU after the first wave (13% vs. 8%). Among all 1374 ICU patients with COVID-19, 326 were admitted during the first wave. There were no major differences in patient's characteristics or mortality between the two periods, but use of invasive mechanical ventilation (81% vs. 58% of patients), renal replacement therapy (26% vs. 13%) and ECMO (8% vs. 3%) and median length of stay in ICU (13 vs. 10 days) and in hospital (20 vs. 17 days) were all significantly lower after the first wave. Risk factors for death were higher age, larger burden of comorbidities (heart failure, pulmonary disease and kidney disease) and active cancer, but not admission during or after the first wave. CONCLUSIONS: After the first wave of COVID-19 in Denmark, a lower proportion of hospitalised patients with COVID-19 were admitted to ICU. Among ICU patients, use of organ support was lower and length of stay was reduced, but mortality rates remained at a relatively high level.