Introduction
The purpose of this study is to describe the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV2) disease characteristics and management in children admitted to the pediatric ...intensive care units (PICU).
Methods
The present study was based on a national multicentric prospective registry including PICU patients with SARS‐CoV2 infection or symptoms of multisystem inflammatory syndrome in children (MIS‐C).
Results
A total of 298 patients were admitted to 41 different Spanish PICUs. A total of 76% of them were previously healthy. The most frequent manifestation was MIS‐C (69.8%). On admission, 59.4% of patients did not have respiratory distress, and only 17.4% needed conventional mechanical ventilation (MV). The need for MV was associated with age (incidence rate ratios IRR 1.21, p < .012), pediatric sequential organ failure assessment score (p‐SOFA) Score (IRR 1.12, p = .001), and need for transfusion (IRR 4.5, p < .004) in MIS‐C patients, and with vasoactive drug use (IRR 2.73, p = .022) and the diagnosis of acute respiratory distress syndrome (IRR 2.83, p = .018) in patients admitted for other reasons. During the first day of admission, 56% of patients met shock criteria and 50.7% needed vasoactive drugs. In MIS‐C patients, their use was associated with higher p‐SOFA score (IRR 1.06, p < .001) and with the diagnosis of shock (IRR 5.78, p < .001). In patients without MIS‐C, it was associated with higher p‐SOFA score (IRR 1.05, p = .022). The mortality rate was 3%, being lower in MIS‐C patients compared to patients admitted for other reasons (0.5% vs. 9.4%, p < .001). It was also lower in previously healthy patients compared to patients with previous comorbidities (0.9% vs. 9.7%, p < .001).
Conclusions
Severe SARS‐CoV2 infection is uncommon in the pediatric population. In our series, respiratory distress was rare, being MIS‐C the most frequent cause of PICU admission related to SARS‐CoV2. In most cases, the course of the disease was mild except in children with previous diseases.
In recent years, the use of transplanted living cells pumping out active factors directly at the site has proven to be an emergent technology. However a recurring impediment to rapid development in ...the field is the immune rejection of transplanted allo- or xenogeneic cells. Immunosuppression is used clinically to prevent rejection of organ and cell transplants in humans, but prolonged usage can make the recipient vulnerable to infections, and increase the likelihood of tumorigenesis of the transplanted cells. Cell microencapsulation is a promising tool to overcome these drawbacks. It consists of surrounding cells with a semipermeable polymeric membrane. The latter permits the entry of nutrients and the exit of therapeutic protein products, obtaining in this way a sustained delivery of the desirable molecule. The membrane isolates the enclosed cells from the host immune system, preventing the recognition of the immobilization cells as foreign. This review paper intends to overview the current situation in the cell encapsulation field and discusses the main events that have occurred along the way. The technical advances together with the ever increasing knowledge and experience in the field will undoubtedly lead to the realization of the full potential of cell encapsulation in the future.
In recent years, virtual reality (VR) has emerged as a new safe and effective tool for neurorehabilitation of different childhood and adulthood conditions. VR-based therapies can induce cortical ...reorganization and promote the activation of different neuronal connections over a wide range of ages, leading to contrasted improvements in motor and functional skills. The use of VR for the visual rehabilitation in amblyopia has been investigated in the last years, with the potential of using serious games combining perceptual learning and dichoptic stimulation. This combination of technologies allows the clinician to measure, treat, and control changes in interocular suppression, which is one of the factors leading to cortical alterations in amblyopia. Several clinical researches on this issue have been conducted, showing the potential of promoting visual acuity, contrast sensitivity, and stereopsis improvement. Indeed, several systems have been evaluated for amblyopia treatment including the use of different commercially available types of head mounted displays (HMDs). These HMDs are mostly well tolerated by patients during short exposures and do not cause significant long-term side effects, although their use has been occasionally associated with some visual discomfort and other complications in certain types of subjects. More studies are needed to confirm these promising therapies in controlled randomized clinical trials, with special emphasis on the definition of the most adequate planning for obtaining an effective recovery of the visual and binocular function.
The coexistence of obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD) leads to increased morbidity and mortality. The development of home-based screening tests ...is essential to expedite diagnosis. Nevertheless, there is still very limited evidence on the effectiveness of portable monitoring to diagnose OSAS in patients with pulmonary comorbidities.
To assess the influence of suffering from COPD in the performance of an oximetry-based screening test for moderate-to-severe OSAS, both in the hospital and at home.
A total of 407 patients showing moderate-to-high clinical suspicion of OSAS were involved in the study. All subjects underwent (i) supervised portable oximetry simultaneously to in-hospital polysomnography (PSG) and (ii) unsupervised portable oximetry at home. A regression-based multilayer perceptron (MLP) artificial neural network (ANN) was trained to estimate the apnea-hypopnea index (AHI) from portable oximetry recordings. Two independent validation datasets were analyzed: COPD versus non-COPD.
The portable oximetry-based MLP ANN reached similar intra-class correlation coefficient (ICC) values between the estimated AHI and the actual AHI for the non-COPD and the COPD groups either in the hospital (non-COPD: 0.937, 0.909-0.956 CI95%; COPD: 0.936, 0.899-0.960 CI95%) and at home (non-COPD: 0.731, 0.631-0.808 CI95%; COPD: 0.788, 0.678-0.864 CI95%). Regarding the area under the receiver operating characteristics curve (AUC), no statistically significant differences (p >0.01) between COPD and non-COPD groups were found in both settings, particularly for severe OSAS (AHI ≥30 events/h): 0.97 (0.92-0.99 CI95%) non-COPD vs. 0.98 (0.92-1.0 CI95%) COPD in the hospital, and 0.87 (0.79-0.92 CI95%) non-COPD vs. 0.86 (0.75-0.93 CI95%) COPD at home.
The agreement and the diagnostic performance of the estimated AHI from automated analysis of portable oximetry were similar regardless of the presence of COPD both in-lab and at-home. Particularly, portable oximetry could be used as an abbreviated screening test for moderate-to-severe OSAS in patients with COPD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aim: To analyze the levels of chronic fatigue in Spanish women with endometriosis and its relationship with their psychosocial status and quality of life (QoL). Methods: A total of 230 Spanish women ...with a clinical diagnosis of endometriosis were recruited. Chronic fatigue (Piper Fatigue Scale) and pelvic pain (Numeric Rating Scale) were evaluated. An on-line battery of validated scales was used to assess psychosocial status Hospital Anxiety and Depression Scale, Scale for Mood Assessment, Pain Catastrophizing Scale, Pittsburgh Sleep Quality Index, Gastrointestinal Quality of Life Index, Female Sexual Function Index and Medical Outcomes Study-Social Support Survey and QoL Endometriosis-Health Profile questionnaire-30. Associations between fatigue and both psychosocial and QoL outcomes were explored through multivariate regression models. Results: One-third and one-half of women showed moderate and severe fatigue, respectively. Fatigue was associated with higher anxiety and depression, poorer sleep quality, poorer sexual functioning, worse gastrointestinal health, higher catastrophizing thoughts, higher anger/hostility scores and lower QoL (p-values < 0.050). Moreover, fatigue and catastrophizing thoughts showed a mediating effect on the association between pelvic pain and QoL. Conclusion: This work reveals the important role of fatigue in the association between pain, psychosocial status, and QoL of Spanish women with endometriosis.
Chitosan (CS) and poly(vinyl alcohol) (PVA) hydrogels, a polymeric system that shows a broad potential in biomedical applications, were developed. Despite the advantages they present, their ...mechanical properties are insufficient to support the loads that appear on the body. Thus, it was proposed to reinforce these gels with inorganic glass particles (BG) in order to improve mechanical properties and bioactivity and to see how this reinforcement affects levofloxacin drug release kinetics. Scanning electron microscopy (SEM), X-ray diffraction (XRD), swelling tests, rheology and drug release studies characterized the resulting hydrogels. The experimental results verified the bioactivity of these gels, showed an improvement of the mechanical properties and proved that the added bioactive glass does affect the release kinetics.
Abstract
Background
Multidrug-resistant Gram-negative bacterial (MRGNB) infections represent a major public health threat. Cancer patients and, among them, hematological patients are most vulnerable ...to these infections. Gut colonization by MRGNB is a common phenomenon occurring during hospitalization and chemotherapy exposure. In the neutropenic phase that occurs after chemotherapy, MRGNB translocation occurs increasing patient’s mortality. Fluoroquinolone prophylaxis with ciprofloxacin or levofloxacin efficacy is now being questioned due to the increase of incidence in MRGNB.
Methods
A phase III randomized, controlled, clinical trial, open-label parallel-group with a 1:1 ratio, aimed to demonstrate the non-inferiority of oral fosfomycin versus oral ciprofloxacin for febrile neutropenia prevention in patients with acute leukemia (AL) or hematopoietic cell transplant (HSC) receptors. Weekly surveillance cultures are planned to detect gut colonization. Changes in fecal microbiome at the beginning and end of prophylaxis will also be analyzed.
Discussion
This trial will provide evidence of the efficacy of an alternative drug to ciprofloxacin for febrile neutropenia prevention in high-risk hematological patients. The battery of planned microbiological studies will allow us to evaluate prospectively the microbiological safety of both pharmacological strategies in terms of the selection of MRGNB occurring in each arm. In addition, valuable information on the way in which each drug changes the fecal microbiome of the patients throughout the treatment will be generated.
Trial registration
Clinical trials NCT05311254, Registered on 5 April 2022,
https://clinicaltrials.gov/ct2/show/NCT05311254?term=FOVOCIP&cntry=ES&draw=2&rank=1
. Protocol version: 3.0, dated 20 May 2022.
Cardiovascular disease is the leading cause of death worldwide. New therapeutic strategies are aimed to modulate the athero-inflammatory process that partially orchestrates underlying vascular ...damage. Peripheral blood circulating cells include different immune cells with a central role in the development of the atherogenic inflammatory response. The anti-aging protein α-Klotho has been related to protective effects against CVD. KL is expressed in monocytes, macrophages, and lymphocytes where it exerts anti-inflammatory effects. In this work, we analyse the relationships of the levels of inflammatory markers with the expression of the KL gene in PBCCs and with the serum levels of soluble KL in atherosclerotic vascular disease. For this, we conducted a cross-sectional single-center case-control study including a study group of 76 CVD patients and a control group of 16 cadaveric organ donors without medical antecedent or study indicating CVD. Vascular artery fragments and whole blood and serum samples were obtained during elective or organ retrieval surgery. Serum levels of sKL, TNFα and IL10, and gene expression levels of KL, TNF, IL10, NFKB1, DNMT1, and DNMT3A in PBCCs were measured. In these cells, we also determined KL promoter methylation percentage. Histological and immunohistochemical analyses were employed to visualize atherosclerotic lesions and to measure IL10 and TNFα levels in vascular fragments. Patients with CVD presented higher values of proinflammatory markers both at systemic and in the vasculature and in the PBCCs, compared to the control group. In PBCCs, CVD patients also presented lower gene expression levels of KL gene (56.4% difference, P < 0.001), higher gene expression levels of DNMT1 and DNMT3A (P < 0.0001, for both) and a higher methylation status of in the promoter region of KL (34.1 ± 4.1% vs. 14.6 ± 3.4%, P < 0.01). In PBCCs and vasculature, KL gene expression correlated inversely with pro-inflammatory markers and directly with anti-inflammatory markers. sKL serum levels presented similar associations with the expression levels of pro- and anti-inflammatory markers in PBCCs. The differences in KL expression levels in PBCCs and in serum sKL levels with respect to control group was even greater in those CVD patients with macroscopically observable atheromatous plaques. We conclude that promoter methylation-mediated downregulation of KL gene expression in PBCCs is associated with the pro-inflammatory status in atherosclerotic vascular disease.
Considering the high prevalence and the complex pharmacological management of immune-mediated inflammatory diseases (IMIDs), the search for new therapeutic approaches for their treatment is vital. ...Although the immunomodulatory and anti-inflammatory effects of mesenchymal stromal cells (MSCs) have been extensively studied as a potential therapy in this field, direct MSC implantation presents some limitations that could slow down the clinical translation. Since the beneficial effects of MSCs have been mainly attributed to their ability to secrete a plethora of bioactive factors, their secretome has been proposed as a new and promising pathway for the treatment of IMIDs. Formed from soluble factors and extracellular vesicles (EVs), the MSC-derived secretome has been proven to elicit immunomodulatory effects that control the inflammatory processes that occur in IMIDs. This article aims to review the available knowledge on the MSC secretome, evaluating the advances in this field in terms of its composition, production and application, as well as analyzing the pending challenges in the field. Moreover, the latest research involving secretome administration in IMIDs is discussed to provide an updated state-of-the-art for this field. Finally, novel secretome delivery alternatives are reviewed, paying special attention to hydrogel encapsulation as one of the most convenient and promising strategies.
In patients with non-severe acute or chronic autoimmune hepatitis (AIH) without cirrhosis, clinical practice guidelines recommend indistinct use of prednisone or budesonide. However, budesonide is ...infrequently used in clinical practice. We aimed to describe its use and compare its efficacy and safety with prednisone as first-line options.
This was a retrospective, multicenter study of 105 naive AIH patients treated with budesonide as the first-line drug. The control group included 276 patients treated with prednisone. Efficacy was assessed using logistic regression and validated using inverse probability of treatment weighting propensity score. The median time to biochemical response (BR) was 3.1 months in patients treated with budesonide and 4.9 months in those with prednisone. The BR rate was significantly higher in patients treated with prednisone (87% vs. 49% of patients with budesonide, p < 0.001). The probability of achieving BR, assessed using the inverse probability of treatment weighting propensity score, was significantly lower in the budesonide group (OR = 0.20; 95% CI: 0.11-0.38) at any time during follow-up, and at 6 (OR = 0.51; 95% CI: 0.29-0.89) and 12 months after starting treatment (0.41; 95% CI: 0.23-0.73). In patients with transaminases <2 × upper limit of normal, BR was similar in both treatment groups. Prednisone treatment was significantly associated with a higher risk of adverse events (24.2% vs. 15.9%, p = 0.047).
In the real-life setting, the use of budesonide as first-line treatment is low, and it is generally prescribed to patients with perceived less disease activity. Budesonide was inferior to prednisone as a first-line drug but was associated with fewer side effects.
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