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ESC Heart Failure Jun 2024Guidelines recommend non-invasive positive pressure ventilation (NPPV) for patients with acute decompensated heart failure (ADHF) with an inadequate response to initial...
AIMS
Guidelines recommend non-invasive positive pressure ventilation (NPPV) for patients with acute decompensated heart failure (ADHF) with an inadequate response to initial oxygen therapy. During Japan's coronavirus disease 2019 pandemic, NPPV use in emergency departments (EDs) was limited due to aerosol-spreading concerns. This study compared the respiratory management and clinical outcomes of patients with ADHF in EDs before and during the pandemic.
METHODS AND RESULTS
This retrospective cohort study was conducted at a single centre in Japan using hospital data from September to November 2019 (before the pandemic) and September to November 2020 (during the pandemic). Patients diagnosed with ADHF were included. Patients not responding to standard oxygen therapy were intubated or started on NPPV therapy. The primary outcome measure was discharge after death. The secondary outcomes were length of hospital stay and medical expenses. The study included 37 patients before the pandemic and 36 during the pandemic. No significant differences were found in vital signs or laboratory data between the groups. NPPV utilization decreased significantly from 26 (70.3%) to 7 (19.4%) (P < 0.01). Two patients required intubation during both periods, with no significant differences (P = 0.98). No significant intergroup disparities were observed in discharge after death (1/36 [2.7%] vs. 1/37 [2.7%]; P = 0.19), length of hospital stay (17.5 vs. 19.0 days; P = 0.65), and medical expenses (57 590 vs. 57 600 yen; P = 0.65).
CONCLUSIONS
Despite a large decrease in NPPV use before and during the pandemic, there were no significant differences in discharge after death, hospital stay, or medical expenses.
PubMed: 38946020
DOI: 10.1002/ehf2.14922 -
American Journal of Critical Care : An... Jul 2024Use of noninvasive ventilation in patients with acute respiratory distress syndrome (ARDS) is debated. The COVID-19 pandemic posed challenges due to high patient volumes...
BACKGROUND
Use of noninvasive ventilation in patients with acute respiratory distress syndrome (ARDS) is debated. The COVID-19 pandemic posed challenges due to high patient volumes and worldwide resource strain.
OBJECTIVES
To determine associations between use of noninvasive ventilation in adult patients with moderate to severe ARDS due to SARS-CoV-2 pneumonia, progression to intubation, and hospital mortality.
METHODS
This retrospective cohort study included patients in an institutional COVID-19 registry. Adult patients were included if they were admitted for COVID-19 between March 1, 2020, and March 31, 2022, and developed moderate to severe ARDS. Primary outcomes were progression to intubation and hospital mortality in patients who received noninvasive ventilation or mechanical ventilation. A secondary outcome was successful treatment with noninvasive ventilation without intubation.
RESULTS
Of 823 patients who met inclusion criteria, 454 (55.2%) did not receive noninvasive ventilation and 369 (44.8%) received noninvasive ventilation. Patients receiving noninvasive ventilation were more likely to require mechanical ventilation than were patients not receiving noninvasive ventilation. Among patients requiring endotracheal intubation, those receiving noninvasive ventilation had a higher likelihood of mortality. Patients receiving noninvasive ventilation had lower severity-adjusted odds of survival to discharge without intubation than did patients not receiving noninvasive ventilation.
CONCLUSION
Patients with moderate to severe ARDS due to SARS-CoV-2 pneumonia treated with noninvasive ventilation had increased likelihood of progression to endotracheal intubation and hospital mortality.
Topics: Humans; COVID-19; Male; Female; Retrospective Studies; Middle Aged; Noninvasive Ventilation; Respiratory Distress Syndrome; Hospital Mortality; Aged; Intubation, Intratracheal; SARS-CoV-2; Severity of Illness Index; Respiration, Artificial; Adult
PubMed: 38945818
DOI: 10.4037/ajcc2024663 -
Brain and Behavior Jul 2024To analyze the efficacy and associated factors affecting the prognosis in patients with disturbance of consciousness after hyperbaric oxygen (HBO) treatment.
OBJECTIVE
To analyze the efficacy and associated factors affecting the prognosis in patients with disturbance of consciousness after hyperbaric oxygen (HBO) treatment.
METHODS
A retrospective study was carried out on patients with disorders of consciousness (DOC) receiving HBO treatment from January to January 2022 in the Second Department of Rehabilitation Medicine of the Second Hospital of Hebei Medical University, China.
RESULTS
HBO therapy improved the Glasgow Coma Scale (GCS) and Chinese Nanjing Persistent Vegetative State Scale (CNPVSS), as well as the clinical efficacy in patients with DOC. The comparison of GCS and CNPVSS scores in patients with DOC before and after HBO treatment was all statistically significant, with 325 patients (67.1%) showing effective results and 159 patients (32.9%) having unchanged outcomes. Univariate analysis indicated that there were statistically significant differences in age, HBO intervention time, HBO treatment times, pre-treatment GCS score, and etiology and underlying diseases between the good and poor prognoses groups. Multivariate regression analysis showed that HBO intervention time ≤7 days, HBO treatment > times, high GCS score before HBO treatment, and brain trauma were independent influencing factors in achieving a good prognosis for patients with DOC. Low pre-treatment GCS scores were an independent risk factor for a poor prognosis in patients with brain trauma while being male, late HBO intervention time, fewer HBO treatment times, and low pre-treatment GCS scores were independent risk factors for a poor prognosis in patients with DOC after a stroke. Being ≥50 years of age, late HBO intervention time, and low pre-treatment GCS scores were independent risk factors for a poor prognosis in patients with DOC after hypoxic-ischaemic encephalopathy.
CONCLUSION
HBO therapy can improve the GCS, CNPVSS scores and clinical efficacy in patients with DOC, and the timing of HBO intervention ≤7 days, times of HBO treatment, high pre-treatment GCS score, and brain trauma were the independent influencing factors of good prognosis in patients with DOC.
Topics: Humans; Hyperbaric Oxygenation; Retrospective Studies; Male; Female; Consciousness Disorders; Middle Aged; Adult; Aged; Glasgow Coma Scale; Prognosis; Treatment Outcome; Young Adult; Adolescent; China
PubMed: 38945804
DOI: 10.1002/brb3.3588 -
Antiviral Research Jun 2024The WHO declared the official end of the SARS-CoV-2 caused public health emergency on May 5, 2023, after two years in which the virus infected approximately 750 Mio...
The WHO declared the official end of the SARS-CoV-2 caused public health emergency on May 5, 2023, after two years in which the virus infected approximately 750 Mio individuals causing estimated up to 7 Mio deaths. Likely, the virus will continue to evolve in the human population as a seasonal respiratory pathogen. To now prevent severe infection outcomes in vulnerable individuals, effective antivirals are urgently needed to complement the protection provided by vaccines. SARS-CoV-2 enters its host cell via ACE2 mediated membrane fusion, either at the plasma membrane, if the protease TMPRSS2 is present or via the endosome, in a cathepsin dependent fashion. A small number of positive regulators of viral uptake were described in the literature, which are potentially useful targets for host directed antiviral therapy or biomarkers indicating increased or diminished susceptibility to infection. We identified here by cell surface proximity ligation novel proteins, required for efficient virion uptake. Importantly, chemical inhibition of one of these factors, SLC3A2, resulted in robust reduction of viral replication, to that achieved with a TMPRSS2 inhibitor. Our screen identified new host dependency factors for SARS-CoV-2 entry, which could be targeted by novel antiviral therapies.
PubMed: 38945485
DOI: 10.1016/j.antiviral.2024.105951 -
The Journal of Pediatrics Jun 2024To describe reported adverse events (AEs) associated with elexacaftor/tezacaftor/ivacaftor (ETI) in a pediatric sample with cystic fibrosis (CF) aged 6-18 years, with at...
Reported Adverse Events in a Multicenter Cohort of Patients Ages 6-18 Years with Cystic Fibrosis and at Least one F508del Allele Receiving Elexacaftor/Tezacaftor/Ivacaftor.
OBJECTIVE
To describe reported adverse events (AEs) associated with elexacaftor/tezacaftor/ivacaftor (ETI) in a pediatric sample with cystic fibrosis (CF) aged 6-18 years, with at least one F508del variant, followed at multiple Italian CF centers.
STUDY DESIGN
This was a retrospective, multicenter, observational study. All children receiving ETI therapy from October 2019 to December 2023 were included. We assessed the prevalence and type of any reported potential drug-related AEs, regardless of discontinuation necessity. Persistent AEs were defined as those continuing at the end of the observation period.
RESULTS
Among 608 patients on ETI, 109 (17.9%) reported at least one AE. The majority (N=85, 77.9%) were temporary, with a median duration of 11 days (range 1-441 days). Only 7 (1.1%) patients permanently discontinued treatment, suggesting good overall safety of ETI. The most common AEs leading to discontinuation were transaminase elevations (temporary 14.1%, persistent 25.9%) and urticaria (temporary 41.2%, persistent 7.4%). Creatinine phosphokinase elevation was uncommon. No significant differences in AEs were observed based on sex, age groups (6-11 vs. 12-18 years), or genotype. Pre-existing CF-related liver disease was associated with an increased risk of transaminase elevations. We identified significant variability in the percentage of reported AEs (ANOVA p-value 0·026).
CONCLUSIONS
This real-world study highlights significant variability in reported AEs. Our findings suggest that ETI is a safe and well-tolerated therapy in children and adolescents with CF. However, further long-term safety and effectiveness investigations are warranted.
PubMed: 38945446
DOI: 10.1016/j.jpeds.2024.114176 -
Contemporary Clinical Trials Jun 2024Awake prone positioning is studied extensively during Covid-19 pandemic, but there is very limited evidence on its utility in acute hypoxic respiratory failure caused by...
BACKGROUND
Awake prone positioning is studied extensively during Covid-19 pandemic, but there is very limited evidence on its utility in acute hypoxic respiratory failure caused by bacterial infections or other causes. The aim of our research is to evaluate the impact of awake prone positioning on outcomes in non-intubated adult patients with acute non-Covid19 hypoxemic respiratory failure.
METHODS
This is a multi-center randomized controlled trial (RCT) with a parallel-group design and a 1:1 allocation ratio. Adult patients, admitted to ICU and diagnosed with hypoxemic respiratory failure will be randomly allocated into intervention (awake prone position (APP)) or control group. Our hypothesis is that addition of awake prone positioning to standard oxygen, high flow oxygen therapy and non-invasive ventilation may reduce the need for mechanical ventilation in adult patients diagnosed with acute hypoxemic respiratory failure. Primary outcome is rate of endotracheal intubation; secondary outcomes include intensive care and hospital mortality, duration of mechanical ventilation, length of intensive care and hospital stay and health related quality of life post hospital discharge. Primary and secondary outcomes will be assessed at hospital discharge, 30, 90 days and 1 year following randomisation.
CONCLUSION
The Hyper-AP study will assess the superiority of awake prone positioning versus standard treatment in spontaneously breathing ICU patients diagnosed with hypoxaemic respiratory failure.
PubMed: 38945293
DOI: 10.1016/j.cct.2024.107614 -
Tissue & Cell Jun 2024Injury to internal organs caused by myocardial infarction (MI), although often neglected, is a very serious condition which damages internal organs especially the lungs....
UNLABELLED
Injury to internal organs caused by myocardial infarction (MI), although often neglected, is a very serious condition which damages internal organs especially the lungs. Changes in microcirculation can begin with acute lung injury and result in severe respiratory failure. The aim of this study was to create new approaches that will explain the pathophysiology and treatment of the disease by examining the therapeutic effects of vitamin D (VITD) and Nerolidol (NRD) on the injuries of the lungs caused by MI, and their relationship with asprosin / spexin proteins.
METHODS
Six groups of seven experimental animals each were constituted. Control, VITD (only 50 IU/day during the experiment), NRD (only 100 mg/kg/day during the experiment), MI (200 mg/kg isoproterenol was administered to rats as a single dose subcutaneously), MI+VITD (200 mg/kg isoproterenol +50 IU/day) and MI+NRD (200 mg/kg isoproterenol +100 mg/kg/day) were the six (6) groups constituted. Tissues were analyzed using histopathological and immunohistochemical methods, whereas serum samples were analyzed using ELISA method.
RESULTS
The result of the histopathological study for the MI group showed an observed increase in inflammatory cells, congestion, interalveolar septal thickening, erythrocyteloaded macrophages and fibrosis in the lung tissues. The treatment groups however recorded significant differences with regards to these parameters. In the immunohistochemical analysis, expressions of asprosin and spexin were observed in the smooth muscle structures and interalveolar areas of the vessels and bronchioles of the lung, as well as the bronchiole epithelium. There was no significant difference between the groups in terms of asprosin and spexin expression in the bronchiol epithelium. When immunohistochemical and serum ELISA results were examined, it was observed that asprosin levels increased significantly in the lung tissues of the MI group compared to the control group, decreased significantly in the treatment groups treated with Vitamin D and NRD after MI. While spexin decreased significantly in the MI group compared to the control group, it increased significantly in the MI+VİTD group, but did not change in the MI+NRD group.
CONCLUSION
It was observed that serious injuries occurred in the lungs due to myocardial infarction and that, VITD and NRD treatments had a curative effect on those injuries. It was also observed that Asprosin and Speksin proteins can have effect on mechanisms of both injury and therapy of the lung. Furthermore, the curative effects of VITD are dependent on the expression of asprosin and spexin; whereas the observation indicated that nerolidol could be effective through asprosin-dependent mechanisms and specisin by independent mechanisms.
PubMed: 38945090
DOI: 10.1016/j.tice.2024.102444 -
Signal Transduction and Targeted Therapy Jul 2024The applications of hydrogels have expanded significantly due to their versatile, highly tunable properties and breakthroughs in biomaterial technologies. In this... (Review)
Review
The applications of hydrogels have expanded significantly due to their versatile, highly tunable properties and breakthroughs in biomaterial technologies. In this review, we cover the major achievements and the potential of hydrogels in therapeutic applications, focusing primarily on two areas: emerging cell-based therapies and promising non-cell therapeutic modalities. Within the context of cell therapy, we discuss the capacity of hydrogels to overcome the existing translational challenges faced by mainstream cell therapy paradigms, provide a detailed discussion on the advantages and principal design considerations of hydrogels for boosting the efficacy of cell therapy, as well as list specific examples of their applications in different disease scenarios. We then explore the potential of hydrogels in drug delivery, physical intervention therapies, and other non-cell therapeutic areas (e.g., bioadhesives, artificial tissues, and biosensors), emphasizing their utility beyond mere delivery vehicles. Additionally, we complement our discussion on the latest progress and challenges in the clinical application of hydrogels and outline future research directions, particularly in terms of integration with advanced biomanufacturing technologies. This review aims to present a comprehensive view and critical insights into the design and selection of hydrogels for both cell therapy and non-cell therapies, tailored to meet the therapeutic requirements of diverse diseases and situations.
Topics: Hydrogels; Humans; Cell- and Tissue-Based Therapy; Drug Delivery Systems; Biocompatible Materials; Animals; Tissue Engineering
PubMed: 38945949
DOI: 10.1038/s41392-024-01852-x -
Internal Medicine (Tokyo, Japan) 2024Thrombocytopenia, anasarca, fever, renal dysfunction, and organomegaly (TAFRO) syndrome is an inflammatory disorder with an unclear pathogenesis. We herein report a case...
Thrombocytopenia, anasarca, fever, renal dysfunction, and organomegaly (TAFRO) syndrome is an inflammatory disorder with an unclear pathogenesis. We herein report a case of TAFRO syndrome in remission in a patient who experienced recurrent intracranial bleeding despite a normal platelet count and coagulation system. A further investigation suggested the presence of anti-glycoprotein VI (GPVI) autoantibodies in the plasma, which induced platelet dysfunction and bleeding tendency. No new bleeding or relapse of TAFRO syndrome occurred after immunosuppressive therapy was initiated. These findings may help elucidate the autoimmune pathogenesis of TAFRO syndrome.
Topics: Humans; Autoantibodies; Recurrence; Syndrome; Platelet Membrane Glycoproteins; Cerebral Hemorrhage; Thrombocytopenia; Fever; Female; Middle Aged; Male; Blood Platelet Disorders
PubMed: 38945933
DOI: 10.2169/internalmedicine.2799-23 -
Journal of Gastrointestinal and Liver... Jun 2024During the coronavirus disease 2019 (COVID-19) pandemic a significant proportion of patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19...
BACKGROUND AND AIMS
During the coronavirus disease 2019 (COVID-19) pandemic a significant proportion of patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 infection developed secondary sclerosing cholangitis (SSC) as a hepatobiliary complication.
METHODS
17 patients were endoscopically diagnosed and treated with COVID-19 SSC from February 2020 until October 2022 at our center. We retrospectively reviewed and analyzed the data to define risk factors, establish endoscopic treatment options, and to estimate incidence and outcomes.
RESULTS
258 patients with COVID-19 infection were admitted to our tertiary center and mechanically ventilated. 10 patients developed COVID-19 SSC in-house, and 7 patients were transferred for further endoscopic treatment. All 17 patients were mechanically ventilated, received vasoactive substances and 12 of them were treated with extracorporeal membrane oxygenation therapy. Endoscopic retrograde cholangiography (ERC) was performed in all patients to establish the diagnosis of COVID-19 SSC and evaluate endoscopic treatment options. All ERCs revealed biliary casts. 9 patients had developed severe rarefication of the intrahepatic bile ducts and 4 showed biliary strictures. As endoscopic treatment approaches, casts were removed repeatedly, and strictures were dilated. During the study period, 14 patients died (82%). 3 patients are in follow-up to reassess the need for liver transplantation.
CONCLUSIONS
COVID-19 SSC was observed in 2.6 % of the patients with severe COVID-19 in our center. We show that endoscopic approaches offer the opportunity to extract casts and to treat biliary strictures. As the mortality rate of COVID-19 SSC is high, endoscopic treatment can be of great clinical relevance as a bridge to liver transplantation.
Topics: Humans; COVID-19; Male; Female; Cholangitis, Sclerosing; Middle Aged; Retrospective Studies; Cholangiopancreatography, Endoscopic Retrograde; Tertiary Care Centers; Aged; SARS-CoV-2; Adult; Treatment Outcome; Risk Factors; Liver Transplantation
PubMed: 38944874
DOI: 10.15403/jgld-5476