The impact of the SARS-CoV-2 pandemic on in-hospital cardiac arrest: A systematic review and meta-analysis.

Background: There is an emerging concern regarding the indirect effect the Covid-19 pandemic has had on the care provided to patients. New resuscitation guidance including the donning of Personal Protective Equipment before commencing resuscitation efforts, the avoidance of bag-mask ventilation, limiting the number of responders and stopping resuscitation efforts earlier could have led to worse outcomes following in-hospital cardiac arrest (IHCA) when compared to the non-pandemic period. The primary objective was to understand the impact of the pandemic on patient outcomes following IHCA by comparing the pandemic and non-pandemic periods. Methods: Our systematic search was conducted on the 13th of September 2022 in three databases: Medline, Embase and Central. Randomised or non-randomised clinical trials and observational studies were included. The search was repeated on 31st December 2023 and there were no new studies appropriate for inclusion which had been published in the interim. The patient population consisted of adult patients who suffered IHCA due to any cause. The primary outcome was survival to hospital discharge (SHD). The secondary outcomes were return of spontaneous circulation (ROSC) and length of resuscitation. Results: We identified 1873 studies, 9 were included in our qualitative analysis. SHD was reported in 8 studies with no difference between the two periods (OR 0.69; 95% CI 0.47-1.03) along with resuscitation (MD: 0.74; 95% CI: -0.67 to 2.14; p = 0.153. ROSC was included in all studies and showed significant difference between the two periods (OR 0.75; 95% 0.60-0.95). Conclusion: Although SHD was similar between the two periods, ROSC was significantly lower during the pandemic with longer resuscitation times highlighting a substantial impact of the pandemic on patient outcomes.

Factors predicting mortality in the cardiac ICU during the early phase of targeted temperature management in the treatment of post-cardiac arrest syndrome - The RAPID score.

Introduction: Survival rates after out-of-hospital cardiac arrest (OHCA) remain low, and early prognostication is challenging. While numerous intensive care unit scoring systems exist, their utility in the early hours following hospital admission, specifically in the targeted temperature management (TTM) population, is questionable. Our aim was to create a score system that may accurately estimate outcome within the first 12 h after admission in patients receiving TTM. Methods: We analyzed data from 103 OHCA patients who subsequently underwent TTM between 2016 and 2022. Patient demographic data, prehospital characteristics, clinical and laboratory parameters were already available in the first 12 h after admission were collected. Following a bootstrap-based predictor selection, we constructed a nonlinear logistic regression model. Internal validation was performed using bootstrap resampling. Discrimination was described using the c-statistic, whereas calibration was characterized by the intercept and slope. Results: According to the Akaike Information Criterion (AIC) heart rate (AIC = 9.24, p = 0.0013), age (AIC = 4.39, p = 0.0115), pH (AIC = 3.68, p = 0.0171), initial rhythm (AIC = 4.76, p = 0.0093) and right ventricular end-diastolic diameter (AIC = 2.49, p = 0.0342) were associated with 30-day mortality and were used to build our predictive model and nomogram. The area under the receiver-operating characteristics curve for the model was 0.84. The model achieved a C-statistic of 0.7974, with internally validated acceptable calibration (intercept: -0.0190, slope: 0.7772) and low error rates (mean absolute error: 0.040). Conclusion: The model we have developed may be suitable for early risk assessment of patients receiving TTM as part of primary post-resuscitation care. The calculator needed for scoring can be accessed at the following link: https://www.rapidscore.eu/.

The investigation of the efficiency of basic life support education among high school students: Protocol, design and implementation of an interventional, prospective longitudinal, individually randomised, parallel 1:1 grouped trial.

Background: Basic life support (BLS) skills are crucial not only for healthcare workers but for all lay people as well. Timely recognition of out-of-hospital cardiac arrest (OHCA) and the initiation of BLS by bystanders before the arrival of healthcare personnel may improve survival. There are several methods of spreading BLS skills and improve BLS skill retention among lay people. One of these methods can be the education of adolescent school children. The introduction of mandatory BLS education in schools was very effective in some European countries to increase the rate of bystander BLS. Methods/design: The current study aims to investigate the efficacy of a BLS training and BLS curriculum among high school children in Hungary. Moreover, the investigators would like to optimise factors influencing skill retention in this first responder group and aim to compare two types of teaching methods: feedback given by the instructor or software-based feedback on the efficacy of chest compressions during the course. This study will be an interventional, assessor blinded, individually randomised parallel group trial recruiting 360 students. BLS skill retention will be assessed at the end of the course, two months after the training and six months after training. Discussion: The current study will increase our knowledge on the methods educating BLS among high school children. The results will help us to create an effective BLS curriculum at schools.Trial registration: ClinicalTrials.gov: NCT06016153. Prospectively registered on 08/2023.

CRISPR/Cas9 Mutagenesis through Introducing a Nanoparticle Complex Made of a Cationic Polymer and Nucleic Acids into Maize Protoplasts.

Presently, targeted gene mutagenesis attracts increasing attention both in plant research and crop improvement. In these approaches, successes are largely dependent on the efficiency of the delivery of gene editing components into plant cells. Here, we report the optimization of the cationic polymer poly(2-hydroxypropylene imine) (PHPI)-mediated delivery of plasmid DNAs, or single-stranded oligonucleotides labelled with Cyanine3 (Cy3) or 6-Carboxyfluorescein (6-FAM)-fluorescent dyes into maize protoplasts. Co-delivery of the GFP-expressing plasmid and the Cy3-conjugated oligonucleotides has resulted in the cytoplasmic and nuclear accumulation of the green fluorescent protein and a preferential nuclear localization of oligonucleotides. We show the application of nanoparticle complexes, i.e., "polyplexes" that comprise cationic polymers and nucleic acids, for CRISPR/Cas9 editing of maize cells. Knocking out the functional EGFP gene in transgenic maize protoplasts was achieved through the co-delivery of plasmids encoding components of the editing factors Cas9 (pFGC-pcoCas9) and gRNA (pZmU3-gRNA) after complexing with a cationic polymer (PHPI). Several edited microcalli were identified based on the lack of a GFP fluorescence signal. Multi-base and single-base deletions in the EGFP gene were confirmed using Sanger sequencing. The presented results support the use of the PHPI cationic polymer in plant protoplast-mediated genome editing approaches.

Early Application of ECMO after Sudden Cardiac Arrest to Prevent Further Deterioration: A Review and Case Report.

ECMO has become a therapeutic modality for in- and out-of-hospital scenarios and is also suitable as a bridging therapy until further decisions and interventions can be made. Case report: A 27-year-old male patient with mechanical aortic valve prothesis had a sudden cardiac arrest (SCA). ROSC had been achieved after more than 60 min of CPR and eight DC shocks due to ventricular fibrillation (VF). The National Ambulance Service unit transported the patient to our clinic for further treatment. Due to the trauma and therapeutic INR, a CT scan was performed and ruled out bleeding. Echocardiography described severely decreased left ventricular function. Coronary angiography was negative. Due to the therapeutic refractory circulatory and respiratory failure against intensive care, VA-ECMO implantation was indicated. After four days of ECMO treatment, the patient's circulation was stabilized without neurological deficit, and the functions of the end organs were normalized. Cardiac MRI showed no exact etiology behind SCA. ICD was implanted due to VF and SCA. The patient was discharged after 19 days of hospitalization. Conclusion: This case report points out that the early application of mechanical circulatory support could be an outcome-determinant therapeutic modality. Post-resuscitation care includes cardiorespiratory stabilization, treatment of reversible causes of malignant arrhythmia, and secondary prevention.

Remote Management of Patients with Cardiac Implantable Electronic Devices during the COVID-19 Pandemic.

Remote monitoring (RM) is the newest function of cardiac implantable electronic devices (CIEDs). In our observational retrospective analysis, we aimed to assess whether telecardiology could be a safe alternative to routine outpatient examinations during the COVID-19 pandemic. The in- and outpatient visits, the number of acute cardiac decompensation episodes, the RM data from CIEDs, and general condition were examined via questionnaires (KCCQ, EQ-5D-5L). Regarding the enrolled 85 patients, the number of personal patient appearances was significantly lower in the year following the pandemic outbreak compared to the previous year (1.4 ± 1.4 and 1.9 ± 1.2, p = 0.0077). The number of acute decompensation events was five before and seven during lockdown (p = 0.6). Based on the RM data, there was no significant difference in heart failure (HF) markers (all related p > 0.05); only patient activity increased after restrictions were lifted compared to that before the lockdown (p = 0.03). During restrictions, patients reported increased anxiety and depression compared to their previous state (p < 0.001). There was no subjective change in the perception of HF symptoms (p = 0.7). Based on the subjective perception and CIED data, the quality of life of patients with CIED did not deteriorate during the pandemic, but their anxiety and depression intensified. Telecardiology may be a safe alternative to routine inpatient examination.

[Cardiopulmonary resuscitation in special circumstances]. / Újraélesztés speciális körülmények között.

The standard process of basic and advanced life support can be complicated by a number of special circumstances. Over the last decade, the European Resuscitation Council developed an increasingly detailed guideline regarding the diagnosis and therapy of these situations. In our short review, we summarize the most important recommendations for the management of cardiopulmonary resuscitation in special circumstances. The proper training in non-technical skills and teamwork is crucial in the management of these situations. In addition, extracorporeal circulatory and respiratory support play an increasingly important role in some special circumstances with appropriate patient selection and timing. We also summarize the therapeutic options regarding the reversible causes of cardiac arrest as well as the steps of diagnostic and treatment methods in some special situations (cardiopulmonary resuscitation in the operating room, after cardiac surgery, in a catheterisation laboratory, after sudden cardiac arrest at dentistry or dialysis station) and among special patient populations (patient with asthma or COPD, neurologic disorders, obese patient, pregnant woman). Orv Hetil. 2023; 164(13): 488-498.

[Impact of the COVID-19 pandemic on basic resuscitation and success rate after sudden cardiac arrest]. / A COVID­19-pandémia hatása a hirtelen szívmegállást követo alapszintu újraélesztésre és annak sikerességére.

Since the onset of the coronavirus disease, infection-related mortality has been tracked worldwide and the number of deaths caused by the virus is counted daily. The coronavirus pandemic has not only transformed our daily life, but reorganized the whole healthcare system. In response to the increased demand for hospital admissions, leaders in different countries have implemented a number of emergency actions. The restructuring has had both direct and indirect negative effects on the epidemiology of sudden cardiac death, the willingness of lay rescuer to give cardiopulmonary resuscitation and the use of automated external defibrillators, but these negative effects vary widely across continents and countries. In order to protect lay people and health workers as well as to prevent the spread of the pandemic, the previous recommendations of the European Resuscitation Council on basic and advanced life support have undergone a few modifications. Orv Hetil. 2023; 164(13): 483-487.

Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials.

Daratumumab has shown clinical benefit in multiple myeloma. We aimed to evaluate the safety and efficacy of adding daratumumab to backbone anti-myeloma treatments. Systematic search was performed up to August 2021 to identify randomised controlled trials comparing the outcomes of backbone therapy with and without daratumumab in relapsed/refractory and newly diagnosed myeloma (RRMM and NDMM, respectively). Odds ratios (ORs) and hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). Primary outcomes were death or disease progression, minimal residual disease (MRD) negativity, and stringent complete response (sCR). Secondary outcomes were complete response or better and safety endpoints prespecified in the study protocol: PROSPERO (CRD42020222904). In NDMM, MRD negativity [OR = 3.61 (CI 2.33-5.61)] and sCR [OR = 2.29 (CI 1.49-3.51)] were more likely and death or disease progression [HR = 0.47 (CI 0.39-0.57)] was less likely to occur with daratumumab compared to control. Regarding RRMM, MRD negativity [OR = 5.43 (CI 2.76-10.66)] and sCR [OR = 3.08 (CI 2.00-4.76)] were more likely and death or disease progression was less likely [HR = 0.50 (CI 0.37-0.67)] with daratumumab compared to control. The addition of daratumumab has shown high clinical efficacy and acceptable toxicity profile for the treatment of NDMM and RRMM regarding the endpoints examined.

Efficacy of first-line treatment options in transplant-ineligible multiple myeloma: A network meta-analysis.

BACKGROUND: Despite major therapeutic advances, the rational choice of the most appropriate first-line regimen in newly diagnosed transplant-ineligible multiple myeloma (TIE-MM) is currently undefined. AIM: We aimed to identify the most effective first-line treatment for TIE-MM patients. METHODS: A total of 37 articles, including 34 treatments and 16,681 patients, were included in this Bayesian network meta-analysis. The outcomes of interest were risk ratios (RR) for progression-free survival (PFS) and overall survival (OS). RESULTS: Based on surface under cumulative ranking curve values, daratumumab-bortezomib-melphalan-prednisone (Dara-VMP) and daratumumab-lenalidomide-dexamethasone (Dara-Rd28) showed superiority compared to other combinations regarding 12-, 24-, 36-, and 48-month PFS. Dara-VMP also ranked first for 12-, 24-, 36-, and 48-month OS. CONCLUSION: Our finding supports the incorporation of daratumumab into first-line regimens. Additionally, these results highlight the relative benefit of incorporating novel agents like monoclonal antibodies, immunomodulatory derivatives, and proteasome inhibitors in combination with the currently existing treatment options.

Early changes in laboratory parameters are predictors of mortality and ICU admission in patients with COVID-19: a systematic review and meta-analysis.

Despite the growing knowledge of the clinicopathological features of COVID-19, the correlation between early changes in the laboratory parameters and the clinical outcomes of patients is not entirely understood. In this study, we aimed to assess the prognostic value of early laboratory parameters in COVID-19. We conducted a systematic review and meta-analysis based on the available literature in five databases. The last search was on July 26, 2020, with key terms related to COVID-19. Eligible studies contained original data of at least ten infected patients and reported on baseline laboratory parameters of patients. We calculated weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) with 95% confidence intervals. 93 and 78 studies were included in quantitative and qualitative syntheses, respectively. Higher baseline total white blood cell count (WBC), C-reactive protein (CRP), lactate-dehydrogenase (LDH), creatine kinase (CK), D-dimer and lower absolute lymphocyte count (ALC) (WMDALC = - 0.35 × 109/L [CI - 0.43, - 0.27], p < 0.001, I2 = 94.2%; < 0.8 × 109/L, ORALC = 3.74 [CI 1.77, 7.92], p = 0.001, I2 = 65.5%) were all associated with higher mortality rate. On admission WBC, ALC, D-dimer, CRP, LDH, and CK changes could serve as alarming prognostic factors. The correct interpretation of laboratory abnormalities can guide therapeutic decisions, especially in early identification of potentially critical cases. This meta-analysis should help to allocate resources and save lives by enabling timely intervention.

RING-Type E3 Ubiqitin Ligase Barley Genes (HvYrg1-2) Control Characteristics of Both Vegetative Organs and Seeds as Yield Components.

Previously, studies on RING-type E3 ubiquitin ligases in cereals were preferentially focused on GW2 genes primarily controlling seed parameters in rice and wheat. Here we report cloning two HvYrg genes from barley that share significant homology with rice GW2 gene. In antisense genotypes efficiency of gene silencing varied between genes and transgenic lines: ASHvYrg1: 30-50% and ASHvYrg2: 20-27%. Reduced activity of both genes altered shoot system with increasing number of side shoots. Changes in leaf width, weight, or plant weight and height reached significant levels in some transgenic lines. Lowering expression of the two barley HvYrg genes caused opposite responses in spike development. Plants with ASHvYrg1 gene construct showed earlier heading time and prolonged grain-filling period, while plants from ASHvYrg2 genotype flowered in delay. Digital imaging of root development revealed that down-regulation of HvYrg1 gene variant stimulated root growth, while ASHvYrg2 plants developed reduced root system. Comparison of seed parameters indicated an increase in thousand grain weight accompanied with longer and wider seed morphology. In summary we conclude that in contrast to inhibition of GW2 genes in rice and wheat plants, down-regulation of the barely HvYrg genes caused substantial changes in vegetative organs in addition to alteration of seed parameters.

Relaxed chromatin induced by histone deacetylase inhibitors improves the oligonucleotide-directed gene editing in plant cells.

Improving efficiency of oligonucleotide-directed mutagenesis (ODM) is a prerequisite for wide application of this gene-editing approach in plant science and breeding. Here we have tested histone deacetylase inhibitor treatments for induction of relaxed chromatin and for increasing the efficiency of ODM in cultured maize cells. For phenotypic assay we produced transgenic maize cell lines expressing the non-functional Green Fluorescent Protein (mGFP) gene carrying a TAG stop codon. These transgenic cells were bombarded with corrective oligonucleotide as editing reagent to recover GFP expression. Repair of green fluorescent protein function was monitored by confocal fluorescence microscopy and flow cytometry was used for quantification of correction events. Sequencing PCR fragments of the GFP gene from corrected cells indicated a nucleotide exchange in the stop codon (TAG) from T to G nucleotide that resulted in the restoration of GFP function. We show that pretreatment of maize cells with sodium butyrate (5-10 mM) and nicotinamide (1-5 mM) as known inhibitors of histone deacetylases can cause elevated chromatin sensitivity to DNase I that was visualized in agarose gels and confirmed by the reduced presence of intact PCR template for the inserted exogenous mGFP gene. Maize cells with more relaxed chromatin could serve as an improved recipient for targeted nucleotide exchange as indicated by an average of 2.67- to 3.62-fold increase in GFP-positive cells. Our results stimulate further studies on the role of the condition of the recipient cells in ODM and testing the application of chromatin modifying agents in other, programmable nuclease-based genome-editing techniques in higher plants.

Stress tolerance of transgenic barley accumulating the alfalfa aldose reductase in the cytoplasm and the chloroplast.

Barley represents one of the major crops grown worldwide; its genetic transformation provides an important tool for the improvement of crop quality and tolerance to environmental stress factors. Biotic and abiotic stresses produce reactive oxygen species in the plant cells that can directly oxidize the cellular components including lipid membranes; resulting in lipid peroxidation and subsequently the accumulation of reactive carbonyl compounds. In order to protect barley plants from the effects of stress-produced reactive carbonyls, an Agrobacterium-mediated transformation was carried out using the Medicago sativa aldose reductase (MsALR) gene. In certain transgenic lines the produced MsALR enzyme was targeted to the chloroplasts to evaluate its protective effect in these organelles. The dual fluorescent protein-based method was used for the evaluation of tolerance of young seedlings to diverse stresses; our results demonstrated that this technique could be reliably applied for the detection of cellular stress in a variety of conditions. The chlorophyll and carotenoid content measurements also supported the results of the fluorescent protein-based method and the stress-protective effect of the MsALR enzyme. Targeting of MsALR into the chloroplast has also resulted in increased stress tolerance, similarly to the observed effect of the cytosolic MsALR accumulation. The results of the DsRed/GFP fluorescent protein-based method indicated that both the cytosol and chloroplast accumulation of MsALR can increase the abiotic stress tolerance of transgenic barley lines.

Response of Organ Structure and Physiology to Autotetraploidization in Early Development of Energy Willow Salix viminalis.

The biomass productivity of the energy willow Salix viminalis as a short-rotation woody crop depends on organ structure and functions that are under the control of genome size. Colchicine treatment of axillary buds resulted in a set of autotetraploid S. viminalis var. Energo genotypes (polyploid Energo [PP-E]; 2n = 4x = 76) with variation in the green pixel-based shoot surface area. In cases where increased shoot biomass was observed, it was primarily derived from larger leaf size and wider stem diameter. Autotetraploidy slowed primary growth and increased shoot diameter (a parameter of secondary growth). The duplicated genome size enlarged bark and wood layers in twigs sampled in the field. The PP-E plants developed wider leaves with thicker midrib and enlarged palisade parenchyma cells. Autotetraploid leaves contained significantly increased amounts of active gibberellins, cytokinins, salicylic acid, and jasmonate compared with diploid individuals. Greater net photosynthetic CO2 uptake was detected in leaves of PP-E plants with increased chlorophyll and carotenoid contents. Improved photosynthetic functions in tetraploids were also shown by more efficient electron transport rates of photosystems I and II. Autotetraploidization increased the biomass of the root system of PP-E plants relative to diploids. Sections of tetraploid roots showed thickening with enlarged cortex cells. Elevated amounts of indole acetic acid, active cytokinins, active gibberellin, and salicylic acid were detected in the root tips of these plants. The presented variation in traits of tetraploid willow genotypes provides a basis to use autopolyploidization as a chromosome engineering technique to alter the organ development of energy plants in order to improve biomass productivity.