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1.
Ann Med ; 54(1): 2477-2485, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36102593

RESUMEN

PURPOSE: The COVID-19 pandemic led to exacerbation of mental health symptoms and deterioration in psychological well-being in individuals suffering from schizophrenia. The primary objective of this study is to evaluate the impacts of the COVID-19 pandemic on patients suffering from treatment-resistant schizophrenia (TRS) with auditory verbal hallucinations (AVH) having undergone virtual reality therapy (VRT) or cognitive behavioural therapy (CBT) on their symptomatology. The secondary objective is to identify the differences and similarities in relation to the response to the COVID 19 pandemic between these two groups of patients. METHODS: Qualitative analysis of semi-structured interviews was conducted with 42 patients suffering from TRS who had previously followed VRT or CBT. All interviews were recorded, transcribed, and analysed. RESULTS: Four themes emerged in this study: Psychotherapeutic Interventions, Impact of COVID-19 and Public health and safety policies, Substance use and Psychiatric follow-up. Participants from both groups reported that their therapy was beneficial in controlling AVH. Patients having followed CBT reported more depressive symptoms whereas patients having followed VRT reported more anxious symptoms. CONCLUSIONS: This study offers a first qualitative insight in patients suffering from TRS and the impacts of COVID-19 on them and opens the door to the protective factors of CBT and VRT for this specific population.


Asunto(s)
COVID-19 , Terapia Cognitivo-Conductual , Esquizofrenia , Terapia de Exposición Mediante Realidad Virtual , COVID-19/terapia , Alucinaciones/complicaciones , Alucinaciones/terapia , Humanos , Pandemias , Esquizofrenia/complicaciones , Esquizofrenia/terapia , Esquizofrenia Resistente al Tratamiento
2.
JAMA Netw Open ; 5(9): e2231790, 2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-36107425

RESUMEN

Importance: Relatively little is known about the persistence of symptoms in patients with COVID-19 for more than 1 year after their acute illness. Objective: To assess the health outcomes among hospitalized COVID-19 survivors over 2 years and to identify factors associated with increased risk of persistent symptoms. Design, Setting, and Participants: This was a longitudinal cohort study of patients who survived COVID-19 at 2 COVID-19-designated hospitals in Wuhan, China, from February 12 to April 10, 2020. All patients were interviewed via telephone at 1 year and 2 years after discharge. The 2-year follow-up study was conducted from March 1 to April 6, 2022. Statistical analysis was conducted from April 20 to May 5, 2022. The severity of disease was defined by World Health Organization guideline for COVID-19. Exposures: COVID-19. Main Outcomes and Measures: The main outcome was symptom changes over 2 years after hospital discharge. All patients completed a symptom questionnaire for evaluation of symptoms, along with a chronic obstructive pulmonary disease assessment test (CAT) at 1-year and 2-year follow-up visits. Results: Of 3988 COVID-19 survivors, a total of 1864 patients (median [IQR] age, 58.5 [49.0-68.0] years; 926 male patients [49.7%]) were available for both 1-year and 2-year follow-up visits. The median (IQR) time from discharge to follow-up at 2 years was 730 (719-743) days. At 2 years after hospital discharge, 370 patients (19.8%) still had symptoms, including 224 (12.0%) with persisting symptoms and 146 (7.8%) with new-onset or worsening of symptoms. The most common symptoms were fatigue, chest tightness, anxiety, dyspnea, and myalgia. Most symptoms resolved over time, but the incidence of dyspnea showed no significant change (1-year vs 2-year, 2.6% [49 patients] vs 2.0% [37 patients]). A total of 116 patients (6.2%) had CAT total scores of at least 10 at 2 years after discharge. Patients who had been admitted to the intensive care unit had higher risks of persistent symptoms (odds ratio, 2.69; 95% CI, 1.02-7.06; P = .04) and CAT scores of 10 or higher (odds ratio, 2.83; 95% CI, 1.21-6.66; P = .02). Conclusions and Relevance: In this cohort study, 2 years after hospital discharge, COVID-19 survivors had a progressive decrease in their symptom burden, but those with severe disease during hospitalization, especially those who required intensive care unit admission, had higher risks of persistent symptoms. These results are related to the original strain of the virus, and their relevance to infections with the Omicron variant is not known.


Asunto(s)
COVID-19 , COVID-19/epidemiología , COVID-19/terapia , China/epidemiología , Estudios de Cohortes , Disnea/epidemiología , Estudios de Seguimiento , Hospitalización , Humanos , Estudios Longitudinales , Masculino , Evaluación de Resultado en la Atención de Salud , SARS-CoV-2 , Sobrevivientes
3.
Prague Med Rep ; 123(3): 140-165, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36107444

RESUMEN

Before coronavirus disease 2019 (COVID-19) emerged, proning had been demonstrated to improve oxygenation in those with acute hypoxic respiratory failure and be performed in non-intensive care settings. This benefit was further exemplified by the COVID-19 pandemic, leading to awake prone positioning (APP). We assessed the efficacy of routine APP versus standard care in preventing death and invasive mechanical ventilation (IMV) in non-intubated hypoxic COVID-19 patients. PubMed, Cochrane Library, Scopus, and medRxiv databases were used from January 1st, 2020, to January 15th, 2022, to identify randomized controlled trials (RCTs). Routine APP group were encouraged to be self-prone, whereas the standard care group received care according to local clinical practice and allowed APP crossover as rescue therapy. We included eight COVID-19 RCTs assessing 809 APP vs. 822 standard care patients. APP group had less IMV requirement (26.5% vs. 30.9%; OR - odds ratio 0.77; P=0.03) than the standard care group, with subgroup analysis showing greater benefit (32.5% vs. 39.1%; OR 0.75; P=0.02) for those mainly requiring oxygen support of non-invasive mechanical ventilation (NIMV) and high-flow nasal cannula (HFNC). The time to IMV initiation was similar (mean 8.3 vs. 10.0 days; P=0.66) for patients requiring NIMV and HFNC. Patients mainly receiving supplemental oxygen and non-rebreather masks had improved oxygenation parameters, although not statistically significant. Other outcomes involving all-cause hospital mortality, hospital and ICU (intensive care unit) length of stay, and adverse events were comparable. APP appeared to be an important modality for reducing IMV requirements, especially in those requiring NIMV and HFNC.


Asunto(s)
COVID-19 , Síndrome de Dificultad Respiratoria , COVID-19/terapia , Humanos , Oxígeno , Terapia por Inhalación de Oxígeno/efectos adversos , Posición Prona , Ensayos Clínicos Controlados Aleatorios como Asunto , Vigilia
4.
Medicine (Baltimore) ; 101(35): e30423, 2022 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-36107561

RESUMEN

Coronavirus disease 2019 (COVID-19) in patients with severe impairment of kidney function is associated with high mortality. We evaluated the effect of high dependency renal unit (HDRU), with nephrologists as primary care physicians, as a quality improvement initiative for the management of these patients. This was a quasi-experimental observational study conducted at a tertiary care hospital in western India. Patients hospitalized for COVID-19 with pre-existing end-stage-renal-disease and those with severe AKI requiring dialysis (AKI-D) were included. For the first 2 months, these patients were cared for in medical wards designated for COVID-19, after which HDRU was set up for their management. With nephrologists as primary care providers, the 4 key components of care in HDRU included: care bundles focusing on key nephrology and COVID-19 related issues, checklist-based clinical monitoring, integration of multi-specialty care, and training of nurses and doctors. Primary outcome of the study was in-hospital mortality before and after institution of the HDRU care. Secondary outcomes were dialysis dependence in AKI-D and predictors of death. A total of 238 out of 4254 (5.59%) patients with COVID-19, admitted from 28th March to 30th September 2020, had severe renal impairment (116 AKI-D and 122 end-stage-renal-disease). 145 (62%) had severe COVID-19. From 28th May to 31st August 2020, these patients were managed in HDRU. Kaplan-Meier analysis showed significant improvement in survival during HDRU care [19 of 52 (36.5%) in pre-HDRU versus 35 of 160 (21.9%) in HDRU died, P ≤ .01]. 44 (67.7%) AKI-D survivors were dialysis dependent at discharge. Breathlessness and altered mental status at presentation, development of shock during hospital stay, and leukocytosis predicted mortality. HDRU managed by nephrologists is a feasible and potentially effective approach to improve the outcomes of patients with COVID-19 and severe renal impairment.


Asunto(s)
Lesión Renal Aguda , COVID-19 , Fallo Renal Crónico , Insuficiencia Renal Crónica , Lesión Renal Aguda/terapia , COVID-19/complicaciones , COVID-19/terapia , Humanos , Riñón , Diálisis Renal , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia
5.
Crit Care ; 26(1): 276, 2022 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-36100904

RESUMEN

BACKGROUND: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). METHODS: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. RESULTS: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). CONCLUSIONS: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.


Asunto(s)
COVID-19 , Insuficiencia Respiratoria , COVID-19/terapia , Humanos , Estudios Prospectivos , Insuficiencia Respiratoria/terapia , SARS-CoV-2 , Taquipnea
6.
An Acad Bras Cienc ; 94(4): e20210202, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36102392

RESUMEN

BACKGROUND: Role of Convalescent plasma (COPLA) to treat severe COVID-19 is under investigation. We compared efficacy and safety of COPLA with fresh frozen plasma (FFP) in severe COVID-19 patients. METHODS: One group received COPLA with standard medical care (n = 14), and another group received random donor FFP, as control with standard medical care (n = 15) in severe COVID-19 disease. RESULTS: The proportion of patients free of ventilation at day seven were 78.5% in COPLA group, and 93.3 % in control group were not significant (p= 0.258). However, improved respiratory rate, O2 saturation, SOFA score, and Ct value were observed in the COPLA group. No serious adverse events were noticed by plasma transfusion in both groups.


Asunto(s)
COVID-19 , Plasma , Transfusión de Componentes Sanguíneos/efectos adversos , COVID-19/terapia , Humanos , Inmunización Pasiva/efectos adversos
7.
Front Immunol ; 13: 923286, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36105796

RESUMEN

Objectives: A major challenge for COVID-19 therapy is dysregulated immune response associated with the disease. Umbilical cord mesenchymal stromal cells (UC-MSCs) may be a promising candidate for COVID-19 treatment owing to their immunomodulatory and anti-inflammatory functions. Therefore, this study aimed to evaluate the effectiveness of UC-MSCs inpatients with COVID-19. Method: Medline, Embase, PubMed, Cochrane Library, and Web of Science databases were searched to collect clinical trials concerning UC-MSCs for the treatment of COVID-19. After literature screening, quality assessment, and data extraction, a systematic review and meta-analysis of the included study were performed. Results: This systematic review and meta-analysis were prospectively registered on PROSPERO, and the registration number is CRD42022304061. After screening, 10 studies involving 293 patients with COVID-19 were eventually included. Our meta-analysis results showed that UC-MSCs can reduce mortality (relative risk [RR] =0.60, 95% confidence interval [CI]: [0.38, 0.95], P=0.03) in COVID-19 patients. No significant correlation was observed between adverse events and UC-MSC treatment (RR=0.85, 95% CI: [0.65, 1.10], P=0.22; RR=1.00, 95%CI: [0.64, 1.58], P=1.00). In addition, treatment with UC-MSCs was found to suppress inflammation and improve pulmonary symptoms. Conclusions: UC-MSCs hold promise as a safe and effective treatment for COVID-19. Systematic Review Registartion: PROSPERO, identifier CRD42022304061.


Asunto(s)
COVID-19 , Células Madre Mesenquimatosas , COVID-19/tratamiento farmacológico , COVID-19/terapia , Humanos , Inmunomodulación , Cordón Umbilical
10.
N Engl J Med ; 387(10): 955, 2022 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-36069883
12.
Artículo en Inglés | MEDLINE | ID: mdl-36078640

RESUMEN

Mindfulness-based art therapy has shown to improve psychological well-being. Zentangle is an easy-to-learn, mindfulness-based art therapy suitable for everyone. We reported the transition from face-to-face to online Zentangle workshops in family social services during COVID-19. We explored feedback from face-to-face workshops and the acceptability of an online approach utilizing information communication technology (ICT) to achieve greater service reach, satisfaction, and knowledge and related outcomes. Under the Hong Kong Jockey Club SMART Family-Link Project and in collaboration with Caritas Integrated Family Service Centre-Aberdeen, this study was conducted in two phases: a four-session, face-to-face workshop (phase one) and eleven online single-session workshops (phase two) from September 2019 to September 2020. A total of 305 participants joined the workshops. Phase one participants (n = 11) reported high satisfaction (4.7 out of 5), increases in knowledge (4.2/5) and confidence (3.9/5) towards managing stress, increases in knowledge (4.1/5) and confidence (3.9/5) in showing support and care towards family members, and an increase in knowledge towards strengthening family relationships (4.0/5). Phase two participants (n = 294) also reported high satisfaction (4.7/5) and strongly agreed that ICT helped with learning Zentangle more conveniently, that they had increased knowledge and interest in Zentangle (all 4.7/5), and would definitely join the workshop again (4.8/5). The qualitative data supported the quantitative findings. We are the first to report on the utilization of ICT in an exploratory trial of brief, online Zentangle art workshops targeting the general public, with high satisfaction and positive participant experiences with ICT integration, learning Zentangle, and enhanced psychological and family well-being. This study provided preliminary evidence on the use of ICT to successfully transition face-to-face to online workshops and reach a wider audience.


Asunto(s)
COVID-19 , Atención Plena , COVID-19/terapia , Humanos , Tecnología de la Información , Aprendizaje , Servicio Social
13.
Braz J Med Biol Res ; 55: e12235, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36102417

RESUMEN

Convalescent plasma therapy has shown controversial results in coronavirus disease-19 (COVID-19) patients. We performed a non-randomized case-control study with contemporaneous controls in a hospital in southern Brazil. Patients were selected for treatment with convalescent plasma by medical decision and compared with patients who did not receive plasma and were hospitalized due to COVID-19 at the same time. The outcomes of interest were intensive care unit (ICU) admission and in-hospital death. Patients that received convalescent plasma had lower in-hospital mortality than patients that did not receive plasma (relative risk (RR) 0.48; 95% confidence interval (CI) 0.29 to 0.79) and these results were consistent after changing the subset of control patients. There were no differences regarding ICU admission between groups (RR=0.80; 95%CI: 0.47 to 1.35). In this study, patients that received convalescent plasma for COVID-19 had lower in-hospital mortality, but this finding requires further confirmation given the retrospective nature of the study.


Asunto(s)
COVID-19 , COVID-19/terapia , Estudios de Casos y Controles , Mortalidad Hospitalaria , Humanos , Inmunización Pasiva , Estudios Retrospectivos
14.
PLoS One ; 17(9): e0274314, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36103547

RESUMEN

INTRODUCTION: The global COVID-19 pandemic effects people and the health system. Some international studies reported an increasing number of out-of-hospital cardiac arrest (OHCA). Comparable studies regarding the impact of COVID-19 on incidence and outcome of OHCA are not yet available for Germany. MATERIALS AND METHODS: This epidemiological study from the German Resuscitation Registry (GRR) compared a non-pandemic period (01.03.2018-28.02.2019) and a pandemic period (01.03.2020-28.02.2021) regarding the pandemic-related impact on OHCA care. RESULTS: A total of 18,799 cases were included. The incidence of OHCA (non-pandemic 117.9 vs. pandemic period 128.0/100,000 inhabitants) and of OHCA with resuscitation attempted increased (66.0 vs. 69.1/100,000). OHCA occurred predominantly and more often at home (62.8% vs. 66.5%, p<0.001). The first ECG rhythm was less often shockable (22.2% vs. 20.3%, p = 0.03). Fewer cases of OHCA were observed (58.6% vs. 55.6% p = 0.02). Both the bystander resuscitation rate and the proportion of telephone guided CPR remained stable (38.6% vs. 39.8%, p = 0.23; and 22.3% vs. 22.5%, p = 0.77). EMS arrival times increased (08:39 min vs. 09:08 min, p<0.001). Fewer patients reached a return of spontaneous circulation (ROSC) (45.4% vs. 40.9%, p<0.001), were admitted to hospital (50.2% vs. 45.0%, p<0.001), and discharged alive (13.9% vs. 10.2%, p<0.001). DISCUSSION: Survival after OHCA significantly decreased while the bystander resuscitation rate remained stable. However, longer EMS arrival times and fewer cases of witnessed OHCA may have contributed to poorer survival. Any change to EMS systems in the care of OHCA should be critically evaluated as it may mean a real loss of life-regardless of the pandemic situation.


Asunto(s)
COVID-19 , Reanimación Cardiopulmonar , Servicios Médicos de Urgencia , Paro Cardíaco Extrahospitalario , COVID-19/epidemiología , COVID-19/terapia , Reanimación Cardiopulmonar/efectos adversos , Humanos , Paro Cardíaco Extrahospitalario/epidemiología , Paro Cardíaco Extrahospitalario/etiología , Paro Cardíaco Extrahospitalario/terapia , Pandemias , Sistema de Registros
15.
Int Rev Cell Mol Biol ; 372: 207-293, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36064265

RESUMEN

Messenger RNA (mRNA)-therapies have recently taken a huge step toward clinic thanks to the first mRNA-based medicinal products marketed. mRNA features for clinical purposes are improved by chemical modifications, but the inclusion in a delivery system is a regular requirement. mRNA nanomedicines must be designed for the specific therapeutic purpose, protecting the nucleic acid and facilitating the overcoming of biological barriers. Polymers, polypeptides, and cationic lipids are the main used materials to design mRNA delivery systems. Among them, lipid nanoparticles (LNPs) are the most advanced ones, and currently they are at the forefront of preclinical and clinical evaluation in several fields, including immunotherapy (against infectious diseases and cancer), protein replacement, gene editing and regenerative medicine. This chapter includes an overview on mRNA delivery technologies, with special interest in LNPs, and the most recent advances in their clinical application. Liposomes are the mRNA delivery technology with the highest clinical translation among LNPs, whereas the first clinical trial of a therapeutic mRNA formulated in exosomes has been recently approved for protein replacement therapy. The first mRNA products approved by the regulatory agencies worldwide are LNP-based mRNA vaccines against viral infections, specifically against the 2019 coronavirus disease (COVID-19). The clinical translation of mRNA-therapies for cancer is mainly focused on three strategies: anti-cancer vaccination by means of delivering cancer antigens or acting as an adjuvant, mRNA-engineered chimeric antigen receptors (CARs) and T-cell receptors (TCRs), and expression of antibodies and immunomodulators. Cancer immunotherapy and, more recently, COVID-19 vaccines spearhead the advance of mRNA clinical use.


Asunto(s)
COVID-19 , Nanopartículas , Neoplasias , COVID-19/terapia , Vacunas contra la COVID-19 , Humanos , Lípidos , Liposomas , Neoplasias/terapia , ARN Mensajero/genética , Tecnología
16.
Can Respir J ; 2022: 9914081, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36091330

RESUMEN

The recently diagnosed coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in December 2019 commonly affects the respiratory system. The incidence of acute hypoxic respiratory failure varied among epidemiological studies with high percentage of patients requiring mechanical ventilation with a high mortality. Noninvasive ventilation is an alternative tool for ventilatory support instead of invasive mechanical ventilation, especially with scarce resources and intensive care beds. Initially, there were concerns by the national societies regarding utilization of noninvasive ventilation in acute respiratory failure. Recent publications reflect the gained experience with the safe utilization of noninvasive mechanical ventilation. Noninvasive ventilation has beneficiary role in treatment of acute hypoxic respiratory failure with proper indications, setting, monitoring, and timely escalation of therapy. Patients should be monitored frequently for signs of improvement or deterioration in the clinical status. Awareness of indications, contraindications, and parameters reflecting either success or failure of noninvasive ventilation in the management of acute respiratory failure secondary to COVID-19 is essential for improvement of outcomes.


Asunto(s)
COVID-19 , Ventilación no Invasiva , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Infecciones del Sistema Respiratorio , COVID-19/complicaciones , COVID-19/terapia , Humanos , Hipoxia/complicaciones , Ventilación no Invasiva/efectos adversos , Respiración Artificial/efectos adversos , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Infecciones del Sistema Respiratorio/complicaciones , SARS-CoV-2
17.
Front Endocrinol (Lausanne) ; 13: 989404, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36093098

RESUMEN

Health disparities are a significant cause of concern globally and in the United States. Disparities have been additionally highlighted throughout the ongoing COVID-19 pandemic during which populations of color have been the most affected by the disease. Social determinants of health, race, ethnicity, and gender have all contributed to disparate outcomes and disparities spanning all age groups. Multiple socio-ecological factors contribute to disparities and different strategies have been proposed. The purpose of this paper is to provide an overview of disparities in pediatric treatment and outcomes, with a focus on children with endocrine disorders.


Asunto(s)
COVID-19 , Pandemias , COVID-19/epidemiología , COVID-19/terapia , Niño , Etnicidad , Hormona del Crecimiento , Humanos , Estados Unidos/epidemiología
18.
Swiss Med Wkly ; 152: w30212, 2022 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-36102065

RESUMEN

AIMS OF THE STUDY: Awake prone positioning (aPP) in non-intubated patients with severe SARS-CoV-2-related pneumonia improves oxygenation and reduces the intubation rate, but no early predictors for success or failure of the strategy have been described. The main objective of this study was to assess whether response to the first aPP in terms of PaO2/FiO2, alveolar-arterial gradient (Aa-O2), respiratory rate and PaCO2 could predict the need for intubation. As secondary objective, we assessed the effects of aPP on the same parameters for all the sessions considered together. METHODS: Retrospective analysis of consecutive SARS-CoV-2 pneumonia patients suffering from acute respiratory failure with moderate to severe hypoxaemia for whom aPP was performed for at least 45 minutes based on the prescription of the clinician in charge according to predefined criteria. Respiratory rate, blood gases and oxygenation parameters (PaO2/FiO2 and Aa-O2), before and after the first aPP were compared between patients who were subsequently intubated or not. Effects of all the aPP sessions together were also analysed. RESULTS: One hundred and sixty-six patients were admitted for SARS-CoV-2 pneumonia during the study period. Among them, 50 received aPP lasting at least 45 minutes. Because 17 denied consent for data analysis and 2 were excluded because of a "do not intubate order", 31 patients (for a total of 116 aPP sessions without any severe adverse events reported) were included. Among them, 10 (32.3%) were intubated. Mean age ± standard deviation (SD) was 60 ± 12 years. At ICU admission, respiratory rate was 26 ± 7/minute, median PaO2/FiO2 94 (interquartile range [IQR] 74-116) mm Hg and median Aa-O2 412 (IQR 286-427) mm Hg (markedly increased). Baseline characteristics did not statistically differ between patients who subsequently needed intubation or not. During the first aPP, PaO2/FiO2 increased and Aa-O2 decreased. When comparing patients who later where intubated or not, we observed, in the non intubated group only, a clinically significant decrease in median Aa-O2, from 294 (280-414) to 204 (107-281) mm Hg, corresponding to a 40% (26-56%) reduction, and a PaO2/FiO2 increase, from 103 (84-116) to 162 (138-195), corresponding to an increase of 48% (11-93%). The p value is <0.005 for both. When all the aPP sessions (n = 80) were considered together, aPP was associated with a significant increase in PaO2/FiO2 from 112 (80-132) to 156 (86-183) mm Hg (p <0.001) and Aa-O2 decrease from 304 (244-418) to 224 (148-361) mm Hg (p = 0.001). CONCLUSIONS: Awake pronation in spontaneously breathing patients is feasible, and improves PaO2/FiO2 and Aa-O2. Response to the first session seems to be associated with lower intubation rate.


Asunto(s)
COVID-19 , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , COVID-19/complicaciones , COVID-19/terapia , Humanos , Hipoxia/complicaciones , Hipoxia/terapia , Intubación Intratraqueal/efectos adversos , Posición Prona , Síndrome de Dificultad Respiratoria/terapia , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Estudios Retrospectivos , SARS-CoV-2 , Vigilia
19.
Front Immunol ; 13: 939899, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36045686

RESUMEN

A majority of patients with sepsis surviving the first days in intensive care units (ICU) enter a state of immunosuppression contributing to their worsening. A novel virotherapy based on the non-propagative Modified Virus Ankara (MVA) expressing the human interleukin-7 (hIL-7) cytokine fused to an Fc fragment, MVA-hIL-7-Fc, was developed and shown to enhance innate and adaptive immunity and confer survival advantages in murine sepsis models. Here, we assessed the capacity of hIL-7-Fc produced by the MVA-hIL-7-Fc to improve ex vivo T lymphocyte functions from ICU patients with sepsis. Primary hepatocytes were transduced with the MVA-hIL-7-Fc or an empty MVA, and cell supernatants containing the secreted hIL-7-Fc were harvested for in vitro and ex vivo studies. Whole blood from ICU patients [septic shock = 15, coronavirus disease 2019 (COVID-19) = 30] and healthy donors (n = 36) was collected. STAT5 phosphorylation, cytokine production, and cell proliferation were assessed upon T cell receptor (TCR) stimulation in presence of MVA-hIL-7-Fc-infected cell supernatants. Cells infected by MVA-hIL-7-Fc produced a dimeric, glycosylated, and biologically active hIL-7-Fc. Cell supernatants containing the expressed hIL-7-Fc triggered the IL-7 pathway in T lymphocytes as evidenced by the increased STAT5 phosphorylation in CD3+ cells from patients and healthy donors. The secreted hIL-7-Fc improved Interferon-γ (IFN-γ) and/or Tumor necrosis factor-α (TNF-α) productions and CD4+ and CD8+ T lymphocyte proliferation after TCR stimulation in patients with bacterial and viral sepsis. This study demonstrates the capacity of the novel MVA-hIL-7-Fc-based virotherapy to restore ex vivo T cells immune functions in ICU patients with sepsis and COVID-19, further supporting its clinical development.


Asunto(s)
COVID-19 , Sepsis , Choque Séptico , Animales , COVID-19/terapia , Enfermedad Crítica , Citocinas/metabolismo , Humanos , Interleucina-7/metabolismo , Ratones , Receptores de Antígenos de Linfocitos T/metabolismo , Factor de Transcripción STAT5/metabolismo , Sepsis/terapia
20.
Int J Mol Sci ; 23(17)2022 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-36077421

RESUMEN

Mesenchymal stem cells (MSCs) are multipotent stem cells with the capacity of self-renewal, homing, and low immunogenicity. These distinct biological characteristics have already shown immense potential in regenerative medicine. MSCs also possess immunomodulatory properties that can maintain immune homeostasis when the immune response is over-activated or under-activated. The secretome of MSCs consists of cytokines, chemokines, signaling molecules, and growth factors, which effectively contribute to the regulation of immune and inflammatory responses. The immunomodulatory effects of MSCs can also be achieved through direct cell contact with microenvironmental factors and immune cells. Furthermore, preconditioned and engineered MSCs can specifically improve the immunomodulation effects in diverse clinical applications. These multifunctional properties of MSCs enable them to be used as a prospective therapeutic strategy to treat immune disorders, including autoimmune diseases and incurable inflammatory diseases. Here we review the recent exploration of immunomodulatory mechanisms of MSCs and briefly discuss the promotion of the genetically engineered MSCs. Additionally, we review the potential clinical applications of MSC-mediated immunomodulation in four types of immune diseases, including systemic lupus erythematosus, Crohn's disease, graft-versus-host disease, and COVID-19.


Asunto(s)
COVID-19 , Enfermedades del Sistema Inmune , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , COVID-19/terapia , Citocinas/metabolismo , Humanos , Enfermedades del Sistema Inmune/metabolismo , Inmunidad , Inmunomodulación , Células Madre Mesenquimatosas/metabolismo
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