Doctor's Orders-Why Radiologists Should Consider Adjusting Commercial Machine Learning Applications in Chest Radiography to Fit Their Specific Needs.

This retrospective study evaluated a commercial deep learning (DL) software for chest radiographs and explored its performance in different scenarios. A total of 477 patients (284 male, 193 female, mean age 61.4 (44.7-78.1) years) were included. For the reference standard, two radiologists performed independent readings on seven diseases, thus reporting 226 findings in 167 patients. An autonomous DL reading was performed separately and evaluated against the gold standard regarding accuracy, sensitivity and specificity using ROC analysis. The overall average AUC was 0.84 (95%-CI 0.76-0.92) with an optimized DL sensitivity of 85% and specificity of 75.4%. The best results were seen in pleural effusion with an AUC of 0.92 (0.885-0.955) and sensitivity and specificity of each 86.4%. The data also showed a significant influence of sex, age, and comorbidity on the level of agreement between gold standard and DL reading. About 40% of cases could be ruled out correctly when screening for only one specific disease with a sensitivity above 95% in the exploratory analysis. For the combined reading of all abnormalities at once, only marginal workload reduction could be achieved due to insufficient specificity. DL applications like this one bear the prospect of autonomous comprehensive reporting on chest radiographs but for now require human supervision. Radiologists need to consider possible bias in certain patient groups, e.g., elderly and women. By adjusting their threshold values, commercial DL applications could already be deployed for a variety of tasks, e.g., ruling out certain conditions in screening scenarios and offering high potential for workload reduction.

Look at the future -perceptions of fertility counseling and decision-making among adolescents and their parents in the context of hematopoietic stem cell transplantation-experience of one major center for pediatric stem cell transplantation.

Introduction: Increasing survival rates after hematopoietic stem cell transplantation (HSCT) in childhood should put focus on improving the quality of life as adults. An essential aspect is fertility and its preservation. In order to take advantage of the possibility of fertility preservation, fertility counseling should be provided to patients and their parents prior to gonadotoxic therapies. Methods: The aim of this survey was to analyze the impact of fertility counseling in pediatric stem cell transplantation in patients and their parents using questionnaires designed for the study questions. Fifty-one parents and 7 adolescent patients were interviewed between February 2019 and October 2021 about the counseling, their perceptions of fertility issues, and the nature of decision- making concerning fertility preservation. The study included patients with malignant (e.g., leukemia, lymphoma, neuroblastoma) and nonmalignant diseases (e.g., thalassemia, sickle cell disease, immunodeficiency) who received counseling on fertility preservation before HSCT based on an in-house standard and analysed the impact for both groups. Results: Two-thirds of the study participants were concerned about having children and grandchildren respectively; for half of all respondents, the topic of fertility and fertility preservation proved to be hopeful. Forty percent of the study participants were burdened by the risk of possible fertility limitations after HSCT. Concerns about fertility was particularly significant for parents whose children were advised to undergo fertility preservation. Parents of children <12 years found deciding on appropriate measures more difficult. Parents with children >7 years involved their children in the decision. All study participants agreed that fertility counseling had not negatively affected the parent-child relationship. More than 90% of all study participants were in favor of addressing fertility, its potential limitations and fertility preservation measures before HSCT. There was no significant difference between the malignant and the non-malignant cohort in all study questions. Discussion: Overall, the standardized fertility counseling provided in our center of pediatric stem cell transplantation resulted in high satisfaction among patients and their parents. Multiple counseling on infertility risk, including the younger patients in the decision-making and further options after gonadotoxic therapy may increase the satisfaction of the counseled patients and their parents.

Nurses' knowledge, barriers and practice in the care of patients with delirium in the intensive care unit in Poland-A cross-sectional study.

Background: Delirium is a cognitive disorder that occurs with high frequency in patients in intensive care units and affects patient outcomes. Despite recommendations for monitoring and assessing delirium in the ICU, studies show that it is still not routinely assessed and often remains undiagnosed or misinterpreted as dementia or depression. Aim: The aim of this study was (1) to assess nurses' knowledge and clinical practices regarding delirium, (2) to identify the factors associated with nurses' knowledge, and (3) to define barriers to effective control of delirium. Methods: A cross-sectional study was conducted among 371 ICU nurses in Poland. Results: 53.1% of nurses had never been educated on delirium control resulting in a deficit in knowledge of delirium symptoms, risk factors and complications associated with delirium in ICU patients. Master's degree in nursing (vs. Registered nurses + Bachelor's), female gender, and working in university hospital (vs. other) were positively correlated with nurse's knowledge, while age had a negative impact on knowledge. Delirium is a marginalized state in ICU patients, only 16.4% of nurses assessed delirium routinely and 35.8% assessed delirium occasionally, rarely using validated scales. Barriers to effective delirium control were primarily the lack of a requirement to assess delirium, the difficulty of assessing delirium in intubated patients and nurses' lack of confidence in their ability to use delirium assessment tools. Conclusions: There is an urgent need to educate nurses about delirium and to make delirium assessment obligatory in clinical practice. The area of change should also include a hospital policy on delirium monitoring and management. The study was registered on ClinicalTrials.gov (NCT05384964).

Analgesic Use in Patients during Cardio-Pulmonary Resuscitation.

INTRODUCTION: Cardiopulmonary resuscitation-induced consciousness is a newly recognized phenomenon with an increasing incidence. A return of consciousness during cardiopulmonary resuscitation affects up to 0.9% of cases. Patients may also experience physical pain associated with chest compressions, as most victims of cardiac arrest who are subjected to resuscitative efforts sustain ribs or sternum fractures. METHODS: A rapid review was carried out from August 2021 to December 2022. RESULTS: Thirty-two articles were included in the rapid review. Of these, eleven studies focused on the return of consciousness during CPR, and twenty-one on CPR-induced chest injuries. CONCLUSION: A small number of studies that have dealt with the return of consciousness associated with cardiopulmonary resuscitation made it hard to clearly determine how often this occurs. There were more studies that dealt with chest trauma during resuscitation, but no study considered the use of analgesics. Of note, there was no standardized therapeutic approach as far as the use of analgesics and/or sedatives was considered. This is probably due to the lack of guidelines for analgesic management during cardiopulmonary resuscitation and peri-resuscitative period.

Combined BCL-2 and PI3K/AKT Pathway Inhibition in KMT2A-Rearranged Acute B-Lymphoblastic Leukemia Cells.

Numerous hematologic neoplasms, including acute B-lymphoblastic leukemia (B-ALL), are characterized by overexpression of anti-apoptotic BCL-2 family proteins. Despite the high clinical efficacy of the specific BCL-2 inhibitor venetoclax in acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL), dose limitation and resistance argue for the early exploration of rational combination strategies. Recent data indicated that BCL-2 inhibition in B-ALL with KMT2A rearrangements is a promising intervention option; however, combinatorial approaches have not been in focus so far. The PI3K/AKT pathway has emerged as a possible target structure due to multiple interactions with the apoptosis cascade as well as relevant dysregulation in B-ALL. Herein, we demonstrate for the first time that combined BCL-2 and PI3K/AKT inhibition has synergistic anti-proliferative effects on B-ALL cell lines. Of note, all tested combinations (venetoclax + PI3K inhibitors idelalisib or BKM-120, as well as AKT inhibitors MK-2206 or perifosine) achieved comparable anti-leukemic effects. In a detailed analysis of apoptotic processes, among the PI3K/AKT inhibitors only perifosine resulted in an increased rate of apoptotic cells. Furthermore, the combination of venetoclax and perifosine synergistically enhanced the activity of the intrinsic apoptosis pathway. Subsequent gene expression studies identified the pro-apoptotic gene BBC3 as a possible player in synergistic action. All combinatorial approaches additionally modulated extrinsic apoptosis pathway genes. The present study provides rational combination strategies involving selective BCL-2 and PI3K/AKT inhibition in B-ALL cell lines. Furthermore, we identified a potential mechanistic background of the synergistic activity of combined venetoclax and perifosine application.

Family experiences and attitudes toward care of ICU patients with delirium: A scoping review.

Introduction: The family has an important role in the care of the ICU patient. Research shows that the implementation of non-pharmacological interventions to prevent delirium, including interventions with the family, can reduce the incidence of delirium. The aim of this review was to search the available literature about the experiences and attitudes of family/carers of ICU patients diagnosed with delirium during hospitalization. Methods: A scoping review method was used to map terms relevant to the involvement of relatives in the care of critically ill patients with delirium. To identify studies, the following databases were searched: PubMed, Scopus, EBSCO, Web of Science, and Cochrane Library. The database search was ongoing from 15 July 2022, with a final search on 4 August 2022. Results: Thirteen articles reporting on the experiences and attitudes of family/carers of ICU patients who developed delirium during hospitalization were included in the scoping review. Of the included studies, eight were qualitative studies, three were quantitative studies and two were reviews (systematic review and integrative review). The studies were conducted in North America, Europe, South Africa, and Asia. Our findings show that carers experienced adverse effects associated with delirium in ICU patients such as stress, anxiety, embarrassment, uncertainty, anger, shock. Families/relatives need both emotional and informational support from medical staff. Conclusion: Relatives want to be involved in the care of the delirium patient, although this needs improvement in some aspects of care such as: lack of awareness, family/relatives knowledge of delirium, improved education, and communication with medical staff. Recognition of delirium by families is acceptable and feasible. Family involvement may induce an increased anxiety, but this aspect needs further research.

Patients' and Relatives' Experiences of Delirium in the Intensive Care Unit-A Qualitative Study.

(1) Introduction: Delirium is a cognitive disorder that affects up to 80% of ICU patients and has many negative consequences. The occurrence of delirium in an ICU patient also negatively affects the relatives caring for these patients. The aim of this study was to explore patients' and their families' experiences of delirium during their ICU stay. (2) Method: The study used a qualitative design based on phenomenology as a research method. A semi-structured interview method was used to achieve the aim. The responses of patients and their families were recorded and transcribed, and the data were coded and analyzed. (3) Results: Eight interviews were conducted with past ICU patients who developed delirium during hospitalization and their family members. The mean age of the participants was 71 years. Of the eight patients, 2 (25%) were female and 6 (75%) were male. The relationships of the 8 carers with the patients were wife (in 4 cases), daughter (in 2 cases), and son (in 2 cases). The average length of time a patient stayed in the ICU was 24 days. The following themes were extracted from the interviews: education, feelings before the delirium, pain, thirst, the day after, talking to the family/patient, and return home. (4) Conclusions: Post-delirium patients and their families feel that more emphasis should be placed on information about delirium. Most patients feel embarrassed and ashamed about events during a delirium episode. Patients fear the reaction of their families when delirium occurs. Patients' families are not concerned about their relatives returning home and believe that the home environment will allow them to forget the delirium events more quickly during hospitalization.

Delirium in ICU Patients after Cardiac Arrest: A Scoping Review.

INTRODUCTION: The incidence of delirium in the intensive care unit is high, although it may differ according to the specific characteristics of the unit. Despite the rapid development of research on delirium in recent years, the pathophysiological mechanisms leading to the clinical presentation of delirium are still subject to hypotheses. The aim of this review was to describe the incidence of delirium in cardiac arrest survivors and the clinical impact of delirium on patient outcomes. METHODS: A scoping review was conducted in the second quarter of 2022. The number of articles retrieved during each search test was limited to studies conducted between 2010 and 2020. Strict inclusion and exclusion criteria were applied. The last search was conducted in May 2022. RESULTS: A total of 537 records was initially obtained from the databases. After discarding duplicates, selecting titles and abstracts, and then analyzing full-text articles, 7 studies met the inclusion criteria. The incidence of delirium in the cardiac arrest survivor population ranged from 8% to as high as 100%. The length of stay in ICU and hospital was significantly longer in patients with delirium than those without. Ninety-eight percent of patients had cognitive or perceptual impairment and psychomotor impairment. Of the seven studies included in the analysis, the RASS, CAM, and NuDesc scales were used to diagnose delirium. Potential risk factors that may influence the duration of delirium include age and time since resuscitation; propofol use shortened the duration of delirium. CONCLUSION: the incidence of delirium in ICU patients who survived CA is high. Cardiac arrest is an additional predisposing factor for delirium. In cardiac arrest survivors, the occurrence of delirium prolongs the duration of ICU and hospital stay and adversely affects functional outcomes. The most common type of delirium among this population was hypoactive delirium. A large percentage of patients manifested symptoms such as cognitive or perception impairment, psychomotor impairment, and impaired concentration and attention.

Effective tumor cell abrogation via Venetoclax-mediated BCL-2 inhibition in KMT2A-rearranged acute B-lymphoblastic leukemia.

Dysregulation of the intrinsic BCL-2 pathway-mediated apoptosis cascade is a common feature of hematological malignancies including acute B-lymphoblastic leukemia (B-ALL). The KMT2A-rearranged high-risk cytogenetic subtype is characterized by high expression of antiapoptotic protein BCL-2, likely due to the direct activating binding of KMT2A fusion proteins to the BCL2 gene. The BCL-2 inhibitor venetoclax (VEN) has proven great clinical value in other blood cancers, however, data on B-ALL is sparse and past studies have not so far described the effects of VEN on gene and protein expression profiles. Using cell lines and patient-derived in vivo xenograft models, we show BCL-2 pathway-mediated apoptosis induction and decelerated tumor cell counts in KMT2A-rearranged B-ALL but not in other cytogenetic subtypes. VEN treatment of cell line- and patient-derived xenografts reduced blast frequencies in blood, bone marrow, and spleen, and tumor cell doubling times were increased. Growth rates are further correlated with VEN concentrations in blood. In vitro incubation with VEN resulted in BCL-2 dephosphorylation and targeted panel RNA sequencing revealed reduced gene expression of antiapoptotic pathway members BCL2, MCL1, and BCL2L1 (BCL-XL). Reinforced translocation of BAX proteins towards mitochondria induced caspase activation and cell death commitment. Prolonged VEN application led to upregulation of antiapoptotic proteins BCL-2, MCL-1, and BCL-XL. Interestingly, the extrinsic apoptosis pathway was strongly modulated in SEM cells in response to VEN. Gene expression of members of the tumor necrosis factor signaling cascade was increased, resulting in canonical NF-kB signaling. This possibly suggests a previously undescribed mechanism of BCL-2-independent and NF-kB-mediated upregulation of MCL-1 and BCL-XL. In summary, we herein prove that VEN is a potent option to suppress tumor cells in KMT2A-rearranged B-ALL in vitro and in vivo. Possible evasion mechanisms, however, must be considered in subsequent studies.

Non-Pharmacological Nursing Interventions to Prevent Delirium in ICU Patients-An Umbrella Review with Implications for Evidence-Based Practice.

Delirium in ICU patients is a complication associated with many adverse consequences. Given the high prevalence of this complication in critically ill patients, it is essential to develop and implement an effective management protocol to prevent delirium. Given that the cause of delirium is multifactorial, non-pharmacological multicomponent interventions are promising strategies for delirium prevention. (1) Background: To identify and evaluate published systematic review on non-pharmacological nursing interventions to prevent delirium in intensive care unit patients. (2) Methods: An umbrella review guided by the Joanna Briggs Institute was utilized. Data were obtained from PubMed, Scopus, EBSCO, Web of Science, Cochrane Library, and Google Scholar. The last search was conducted on 1 May 2022. (3) Results: Fourteen reviews met the inclusion criteria. Multicomponent interventions are the most promising methods in the fight against delirium. The patient's family is an important part of the process and should be included in the delirium prevention scheme. Light therapy can improve the patient's circadian rhythm and thus contribute to reducing the incidence of delirium. (4) Conclusions: Non-pharmacological nursing interventions may be effective in preventing and reducing the duration of delirium in ICU patients.

Conflict Sources and Management in the ICU Setting before and during COVID-19: A Scoping Review of the Literature.

INTRODUCTION: Conflicts are an inherent part of work within any organisation. They can arise between members of an interdisciplinary team (or between teams representing different departments), between patients and team members/family members, and patients' families and team members. Various conflict situations among employees may occur, therefore it is very important to identify their causes and take preventive or targeted corrective measures. The aim of this study was to review the available literature concerning conflicts arising in ICUs-their types, methods of expression as well as their management and mitigation. In addition, we reviewed the available literature on the impact of the pandemic on the ICU environment caring for COVID-19 patients. METHODS: The databases were searched. Single key words or their combinations using AND or OR operators were entered. Eventually, 15 articles were included in our review, which included two identical papers. RESULTS: Conflicts occurred occasionally or rarely; researchers describing ethical conflicts demonstrated a moderate level of exposure to conflicts. The pandemic created many challenges and ethical dilemmas that are a source of ethical conflict. CONCLUSIONS: As conflict by nature remains inevitable, adequate procedures in conflict management should be developed and the leadership of managing personnel should be reinforced, because team members frequently expect guidance from their supervisors. The importance of training in interpersonal communication and crisis situation management in healthcare should therefore be emphasised.

The Molecular Subtype of Adult Acute Lymphoblastic Leukemia Samples Determines the Engraftment Site and Proliferation Kinetics in Patient-Derived Xenograft Models.

In acute lymphoblastic leukemia (ALL), conventional cell lines do not recapitulate the clonal diversity and microenvironment. Orthotopic patient-derived xenograft models (PDX) overcome these limitations and mimic the clinical situation, but molecular stability and engraftment patterns have not yet been thoroughly assessed. We herein describe and characterize the PDX generation in NSG mice. In vivo tumor cell proliferation, engraftment and location were monitored by flow cytometry and bioluminescence imaging. Leukemic cells were retransplanted for up to four passages, and comparative analyses of engraftment pattern, cellular morphology and genomic hotspot mutations were conducted. Ninety-four percent of all samples were successfully engrafted, and the xenograft velocity was dependent on the molecular subtype, outcome of the patient and transplantation passage. While BCR::ABL1 blasts were located in the spleen, KMT2A-positive cases had higher frequencies in the bone marrow. Molecular changes appeared in most model systems, with low allele frequency variants lost during primary engraftment. After the initial xenografting, however, the PDX models demonstrated high molecular stability. This protocol for reliable ALL engraftment demonstrates variability in the location and molecular signatures during serial transplantation. Thorough characterization of experimentally used PDX systems is indispensable for the correct analysis and valid data interpretation of preclinical PDX studies.

Expert-independent classification of mature B-cell neoplasms using standardized flow cytometry: a multicentric study.

Reproducible expert-independent flow-cytometric criteria for the differential diagnoses between mature B-cell neoplasms are lacking. We developed an algorithm-driven classification for these lymphomas by flow cytometry and compared it to the WHO gold standard diagnosis. Overall, 662 samples from 662 patients representing 9 disease categories were analyzed at 9 laboratories using the previously published EuroFlow 5-tube-8-color B-cell chronic lymphoproliferative disease antibody panel. Expression levels of all 26 markers from the panel were plotted by B-cell entity to construct a univariate, fully standardized diagnostic reference library. For multivariate data analysis, we subsequently used canonical correlation analysis of 176 training cases to project the multidimensional space of all 26 immunophenotypic parameters into 36 2-dimensional plots for each possible pairwise differential diagnosis. Diagnostic boundaries were fitted according to the distribution of the immunophenotypes of a given differential diagnosis. A diagnostic algorithm based on these projections was developed and subsequently validated using 486 independent cases. Negative predictive values exceeding 92.1% were observed for all disease categories except for follicular lymphoma. Particularly high positive predictive values were returned in chronic lymphocytic leukemia (99.1%), hairy cell leukemia (97.2%), follicular lymphoma (97.2%), and mantle cell lymphoma (95.4%). Burkitt and CD10+ diffuse large B-cell lymphomas were difficult to distinguish by the algorithm. A similar ambiguity was observed between marginal zone, lymphoplasmacytic, and CD10- diffuse large B-cell lymphomas. The specificity of the approach exceeded 98% for all entities. The univariate immunophenotypic library and the multivariate expert-independent diagnostic algorithm might contribute to increased reproducibility of future diagnostics in mature B-cell neoplasms.

Engraftment Effects after Intra-Bone Marrow versus Intravenous Allogeneic Stem Cell Transplantation in a Reduced-Intensity Conditioning Dog Leukocyte Antigen-Identical Canine Model.

Following conventional i.v. hematopoietic stem cell transplantation (IV-HSCT), most of the hematopoietic stem cells get trapped in peripheral organs and do not reach the bone marrow niche. A promising approach to overcome this cell loss during the homing process seems to be the infusion of hematopoietic stem cells directly into the bone marrow cavity (intra-bone marrow [IBM]-HSCT). This study aimed to investigate the engraftment efficiency of IBM-HSCT compared with IV-HSCT following reduced-intensity conditioning in a canine HSCT model. Furthermore, the impact of 2 different graft infusion rates during IBM-HSCT on the engraftment was evaluated. Dogs received 4.5 Gy total body irradiation for conditioning at day -1 and 15 mg/kg cyclosporin A twice daily at days -1 to +35 as immunosuppression. The IV-HSCT group (n = 7) received unmodified bone marrow. The IBM-HSCT cohorts received buffy coat-enriched bone marrow that was applied into the humerus and femur simultaneously with an infusion time of either 10 minutes (IBM10; n = 8) or 60 minutes (IBM60; n = 7). Statistical analyses were performed using the Kruskal-Wallis test followed by the Mann-Whitney U test with Bonferroni correction for multiple comparisons. Statistical significance was declared at Bonferroni-adjusted P < .017. All dogs initially engrafted. One dog of the IBM10 cohort died at day +15 from infection. All 21 evaluable dogs developed a durable mixed donor chimerism over the course of 112 days. Engraftment kinetics did not differ significantly across the 3 groups. Leukocyte and platelet nadirs, as well as the durations of leukopenia and thrombocytopenia, were comparable in the 3 groups. Signs of toxicity for ingestion, body temperature, activity, and defecation did not show statistically significant differences among the 3 groups; only weight loss was greater in the IBM60 group compared with the IV group. IBM-HSCT following reduced-intensity conditioning resulted in an engraftment efficiency and hematopoietic recovery comparable to that seen with conventional IV-HSCT. In addition, modification of the graft infusion rate had no impact on engraftment and hematopoietic recovery in the canine IBM-HSCT model.

Delirium in Critical Illness Patients and the Potential Role of Thiamine Therapy in Prevention and Treatment: Findings from a Scoping Review with Implications for Evidence-Based Practice.

INTRODUCTION: Thiamine is a water-soluble vitamin and is necessary for energy metabolism. Critically ill patients are at particular risk of developing thiamine deficiency and related complications. One of the complications that can occur is delirium. Delirium is a disorder that affects the body's response to treatment, length of stay in the ward, mortality, long-term cognitive impairment, and significantly increases treatment costs. In addition, studies show that delirium medication is more effective in preventing than in treating delirium. Given its low cost, availability, and minimal risk of side effects, thiamine supplementation could prove to be a relevant strategy in the prevention and treatment of delirium. METHODS: PubMed, Cochrane Library, Ovid, and ClinicalTrials.gov databases were searched using relevant keywords that focus on the use of thiamine to prevent or treat delirium in critically ill patients. RESULTS: Seven articles were included in the analysis. CONCLUSION: The small number of studies and considerable heterogeneity prevent conclusions supporting the use of thiamine as an adjuvant in the prevention and treatment of delirium among critically ill patients. There is a need for high-quality, large-scale randomized clinical trials to confirm the beneficial effects of thiamine in the prevention and treatment of delirium.

Carbapenem-Resistant Klebsiella pneumoniae Infections in ICU COVID-19 Patients-A Scoping Review.

INTRODUCTION: The spread of multidrug-resistant pathogens is a serious problem and challenge for the whole medical community. Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in immunocompromised patients have a severe course and may be fatal. Increasingly, these bacteria are exhibiting resistance to carbapenem antibiotics, which have been used as so-called drugs of last resort. The emergence of the new coronavirus and the pandemic that it has caused require changes to protect against the spread of the new SARS-CoV-2. These changes paradoxically may contribute to the spread of other infections. METHODS: PubMed, Cochrane Library databases were searched using relevant keywords. A literature review of carbapenem-resistant Klebsiella pneumoniae infection in patients hospitalized for COVID-19 was conducted according to PRISMA recommendations. A written review protocol was not prepared. RESULTS: 1016 studies in scientific databases were searched. After rejecting duplicate studies, 964 results were obtained. Inclusion and exclusion criteria were then applied, and studies were qualitatively analyzed. Finally, 11 studies were included in the review. The results of infected patients were from six countries. The prevalence of CRKP in Covid-19 patients ranged from 0.35-53%. The majority of CRKP infected patients were male (85%), with a mean age of 61 years. Among isolates, the predominant genes were KPC, OXY-48, CTX-M, TEM, NDM and SHV. CONCLUSION: The results presented in our review indicate the necessity of paying attention to carbapenem-resistant Klebsiella pneumoniae infections in patients with COVID-19. In order to prevent the increase of bacterial resistance, rational antibiotic therapy should be used, as well as continuous control and surveillance of hospital infections caused by multidrug-resistant organisms.

The Accuracy of On-Call CT Reporting in Teleradiology Networks in Comparison to In-House Reporting.

(1) Background: We aimed to compare the accuracy of after-hours CT reports created in a traditional in-house setting versus a teleradiology setting by assessing the discrepancy rates between preliminary and final reports. (2) Methods: We conducted a prospective study to determine the number and severity of discrepancies between preliminary and final reports for 7761 consecutive after-hours CT scans collected over a 21-month period. CT exams were performed during on-call hours and were proofread by an attending the next day. Discrepancies between preliminary and gold-standard reports were evaluated by two senior attending radiologists, and differences in rates were assessed for statistical significance. (3) Results: A total of 7209 reports were included in the analysis. Discrepancies occurred in 1215/7209 cases (17%). Among these, 433/7209 reports (6%) showed clinically important differences between the preliminary and final reports. A total of 335/5509 of them were in-house reports (6.1%), and 98/1700 were teleradiology reports (5.8%). The relative frequencies of report changes were not significantly higher in teleradiology. (4) Conclusions: The accuracy of teleradiology reports was not inferior to that of in-house reports, with very similar clinically important differences rates found in both reporting situations.

Combined Application of Pan-AKT Inhibitor MK-2206 and BCL-2 Antagonist Venetoclax in B-Cell Precursor Acute Lymphoblastic Leukemia.

Aberrant PI3K/AKT signaling is a hallmark of acute B-lymphoblastic leukemia (B-ALL) resulting in increased tumor cell proliferation and apoptosis deficiency. While previous AKT inhibitors struggled with selectivity, MK-2206 promises meticulous pan-AKT targeting with proven anti-tumor activity. We herein, characterize the effect of MK-2206 on B-ALL cell lines and primary samples and investigate potential synergistic effects with BCL-2 inhibitor venetoclax to overcome limitations in apoptosis induction. MK-2206 incubation reduced AKT phosphorylation and influenced downstream signaling activity. Interestingly, after MK-2206 mono application tumor cell proliferation and metabolic activity were diminished significantly independently of basal AKT phosphorylation. Morphological changes but no induction of apoptosis was detected in the observed cell lines. In contrast, primary samples cultivated in a protective microenvironment showed a decrease in vital cells. Combined MK-2206 and venetoclax incubation resulted in partially synergistic anti-proliferative effects independently of application sequence in SEM and RS4;11 cell lines. Venetoclax-mediated apoptosis was not intensified by addition of MK-2206. Functional assessment of BCL-2 inhibition via Bax translocation assay revealed slightly increased pro-apoptotic signaling after combined MK-2206 and venetoclax incubation. In summary, we demonstrate that the pan-AKT inhibitor MK-2206 potently blocks B-ALL cell proliferation and for the first time characterize the synergistic effect of combined MK-2206 and venetoclax treatment in B-ALL.

Nephrogenic Systemic Fibrosis as a Complication after Gadolinium-Containing Contrast Agents: A Rapid Review.

Introduction: Nephrogenic systemic fibrosis (NFS) is a generalized disorder occurring in people with kidney failure. This new disease entity can lead to significant disability or even death. Gadolinium-associated systemic fibrosis is related to exposure to contrast agents used for magnetic resonance imaging. The aim of this study was to review the literature in available scientific databases on NFS-complication after gadolinium-containing contrast agents. Methods: PubMed and Cochrane Library databases were searched using adequate key words. A literature review of the described cases of NSF occurrence after exposure to gadolinium-containing contrast agents was performed. A review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A review written protocol was not drafted. Results: Originally, 647 studies were searched in scientific databases. After rejecting the duplicate results, 515 results were obtained. Finally, nine studies were included in the review. A total of 173 cases with NSF were included in the analysis. The majority of patients were undergoing dialysis. The contrast agent used for MRI was most often gadodiamide and gadopentetate dimeglumine. The time from exposure to NSF symptoms was from two days to three years. Three authors pointed out other factors in their papers that could potentially influence the occurrence of NSF. These included: metabolic acidosis, ongoing infection, higher doses of erythropoietin and higher serum concentrations of ionized calcium and phosphate. Since 2008, the number of reported cases of NSF has decreased significantly. More recent guidelines and reports indicate that not all contrast agents are associated with the same risk of developing NSF. Conclusions: Most NSF occurs after exposure to linear contrast agents. Therefore, it is recommended to limit their use, especially in dialyzed patients and patients with a GFR < 30 mL/min.

New Deoxyribozymes for the Native Ligation of RNA.

Deoxyribozymes (DNAzymes) are small, synthetic, single-stranded DNAs capable of catalyzing chemical reactions, including RNA ligation. Herein, we report a novel class of RNA ligase deoxyribozymes that utilize 5'-adenylated RNA (5'-AppRNA) as the donor substrate, mimicking the activated intermediates of protein-catalyzed RNA ligation. Four new DNAzymes were identified by in vitro selection from an N40 random DNA library and were shown to catalyze the intermolecular linear RNA-RNA ligation via the formation of a native 3'-5'-phosphodiester linkage. The catalytic activity is distinct from previously described RNA-ligating deoxyribozymes. Kinetic analyses revealed the optimal incubation conditions for high ligation yields and demonstrated a broad RNA substrate scope. Together with the smooth synthetic accessibility of 5'-adenylated RNAs, the new DNA enzymes are promising tools for the protein-free synthesis of long RNAs, for example containing precious modified nucleotides or fluorescent labels for biochemical and biophysical investigations.