Indirectly determined hematology reference intervals for pediatric patients in Berlin and Brandenburg

Objectives Establishing direct reference intervals (RIs) for pediatric patients is a very challenging endeavor. Indirectly determined RIs can address this problem by utilization of existing clinical laboratory databases. In order to provide better laboratory services to the local pediatric population, we established population-specific hematology RIs via data mining. Methods Our laboratory information system (LIS) was searched for pediatric blood counts of patients aged from 0 days to 18 years, performed from 1st of January 2018 until 31st of March 2021. In total, 27,554 blood counts on our SYSMEX XN-9000 were initially identified. After application of pre-defined exclusion criteria, 18,531 sample sets remained. Age- and sex-specific RIs were established in accordance with International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and Clinical & Laboratory Standards Institute (CLSI) recommendations. Results When compared to pediatric RIs supplied by other authors, the RIs determined specifically for pediatric patients from Berlin and Brandenburg showed several relevant differences, especially with regard to white blood cell counts (WBCs), red blood cell counts (RBCs), red cell distribution widths (RDW) and platelet counts (PLTs) within the distinct age groups. Additionally, alterations to several published age-specific partitions had to be made, while new sex-specific partitions were introduced for WBCs and PLTs. Conclusions Generic RIs from textbooks, manufacturer information and medical publications – even from nationwide or multicenter studies – commonly used in many laboratories might not reflect the specifics of local patient populations properly. RIs should be tailored to the serviced patient population whenever possible. Careful data mining appears to be suitable for this task.

Tissue Microarray from Cell Block Material (cbTMA)—An Additional Shot for Cytology in the Predictive Pathology Era: The PD-L1 Experience

Generally, predictive biomarker tests are clinically validated on histological formalin-fixed, paraffin-embedded (FFPE) samples. In addition to FFPE samples, cytological samples have also emerged as a useful approach to detect predictive biomarkers. However, as of today, despite the promising results reported in the recent literature, their full implementation in routine clinical practice is still lagging owing to a lack of standardized preparatory protocols, challenging assessments of cyto-histological correlation, and variable inter-observer agreement. The aim of this report was to explore the possibility of implementing a large-scale validation of predictive biomarker testing on cytological material. To this aim, we evaluated the technical feasibility of PD-L1 assessment on a cell block (CB)-derived tissue microarray (cbTMA). Consecutive and unselected CBs prepared from metastatic lymph node fine-needle cytology (FNC) samples were retrospectively collected and used for TMA construction. PD-L1 immunohistochemistry (IHC) was carried out on cbTMA sections with the companion diagnostic kit SP263 assay. TMA contained 33 CB-derived cores. A total of 20 sections were hematoxylin and eosin (H&E) stained. Overall, 29 (88%) samples were visible at least in one H&E-stained slide. Four cases out of five sections stained with the SP263 assay (4/29, 13.8%) showed PD-L1 positivity in neoplastic and/or immune cells; remarkably, no unspecific background was observed. Although our study was based on a limited and non-selected series, our findings do provide proof of concept for the use of cbTMA in predictive biomarker testing on cytological material in large-scale post-clinical trial validation studies, multicenter studies, and quality control programs.

The place of combined mucoactive drugs in the treatment of acute respiratory infections in children

The problem of respiratory diseases and their therapy options still retains much of its urgency. Respiratory diseases in children are still super common. According to the data on infectious morbidity among children in the Russian Federation for the period 2018–2020, current trends have not changed, and the acute respiratory infections (ARI) are still ranked number one in terms of the frequency of registered diseases. According to the official records, the frequency of ARI in children among infectious diseases is 71,850.02 per 100,000 population, or 71%. Such well-known symptom as cough is one of the most frequent manifestations of respiratory diseases. It causes the greatest discomfort for both the little patients and their parents, the quality of life of the children and those around them worsens, many domestic and foreign authors mention this symptom in their works. And it is this problem that doctors of various specialties most often face. The cough is currently treated with drugs with different effects depending on the characteristics and manifestations of the disease. Systematic reviews and multicenter studies show that prescription of mucoactive drugs to treat cough in children with underlying ARI is substantiated and feasible. The authors substantiated the necessity of using combinations of various drugs aimed to reduce inflammation of the airways, improve mucociliary clearance, thin out and promote sputum discharge and, accordingly, reduce cough. The article briefly discusses the mechanisms of the development of cough in ARI, the action of drug substances included in the combination drugs used to treat cough in children, the possibility of using the combination of muco- and bronchoactive drugs of synthetic and plant origin.

Using Observational Study Data as an External Control Group for a Clinical Trial: an Empirical Comparison of Methods to Account for Longitudinal Missing Data

Background: Observational data are increasingly being used to conduct external comparisons to clinical trials. In this study, we empirically examined whether different methodological approaches to longitudinal missing data affected study conclusions in this setting. Methods: We used data from one clinical trial and one prospective observational study, both Norwegian multicenter studies including patients with recently diagnosed rheumatoid arthritis and implementing similar treatment strategies, but with different stringency. A binary disease remission status was defined at 6, 12, and 24 months in both studies. After identifying patterns of longitudinal missing outcome data, we evaluated the following five approaches to handle missingness: analyses of patients with complete follow-up data, multiple imputation (MI), inverse probability of censoring weighting (IPCW), and two combinations of MI and IPCW. Results: We found a complex non-monotone missing data pattern in the observational study (N=328), while missing data in the trial (N=188) was monotone due to drop-out. In the observational study, only 39.0% of patients had complete outcome data, compared to 89.9% in the trial. All approaches to missing data indicated favorable outcomes of the treatment strategy in the trial and resulted in similar study conclusions. Variations in results across approaches were mainly due to variations in estimated outcomes for the observational data. Conclusions: Five different approaches to handle longitudinal missing data resulted in similar conclusions in our example. However, the extent and complexity of missing observational data affected estimated comparative outcomes across approaches, highlighting the need for careful consideration of methods to account for missingness when using observational data as external controls to trial data.

Invasive pulmonary aspergillosis among intubated patients with SARS-CoV-2 or influenza pneumonia: a European multicenter comparative cohort study

Background Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients. Objectives To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza patients. Methods This study was a planned ancillary analysis of the coVAPid multicenter retrospective European cohort. Consecutive adult patients requiring invasive mechanical ventilation for > 48 h for SARS-CoV-2 pneumonia or influenza pneumonia were included. The 28-day cumulative incidence of putative IPA, based on Blot definition, was the primary outcome. IPA incidence was estimated using the Kalbfleisch and Prentice method, considering extubation (dead or alive) within 28 days as competing event. Results A total of 1047 patients were included (566 in the SARS-CoV-2 group and 481 in the influenza group). The incidence of putative IPA was lower in SARS-CoV-2 pneumonia group (14, 2.5%) than in influenza pneumonia group (29, 6%), adjusted cause-specific hazard ratio (cHR) 3.29 (95% CI 1.53–7.02, p = 0.0006). When putative IPA and Aspergillus respiratory tract colonization were combined, the incidence was also significantly lower in the SARS-CoV-2 group, as compared to influenza group (4.1% vs. 10.2%), adjusted cHR 3.21 (95% CI 1.88–5.46, p < 0.0001). In the whole study population, putative IPA was associated with significant increase in 28-day mortality rate, and length of ICU stay, compared with colonized patients, or those with no IPA or Aspergillus colonization. Conclusions Overall, the incidence of putative IPA was low. Its incidence was significantly lower in patients with SARS-CoV-2 pneumonia than in those with influenza pneumonia. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693.

Areas of Work Life as Predictors of Occupational Burnout of Nurses and Doctors in Operating Theaters in Poland—Multicenter Studies

Introduction: Researchers’ interest in occupational burnout results primarily from the dangerous and extensive consequences of this phenomenon. The aim of the study was to analyze the level of occupational burnout among nurses and doctors in operating theaters. Materials and Methods: A cross-sectional survey study conducted on 325 nurses and doctors of seven hospitals in Poland. The Maslach Burnout Inventory (MBI) and the Areas of Worklife Survey (AWS) by Michael Leiter and Christina Maslach. Results: The mean values for the level of occupational burnout for the entire sample according to the scale from the Maslach Burnout Inventory by C. Maslach amounted to 14.35 for emotional exhaustion, 8.56 for depersonalization, and 11.90 for personal accomplishment; when compared to reference levels, they classified emotional exhaustion at a low level, depersonalization at an average level, and personal accomplishment at a high level of burnout. Areas of work life are predictors of occupational burnout. The analysis showed a relationship between three of the six variables. As the workload increased, so did the level of burnout among participants, and the categories of honesty and values. Conclusions: The conducted research has shown that occupational burnout among nurses and doctors in operating theaters occurs in all dimensions of this phenomenon (emotional exhaustion, depersonalization, job satisfaction). It was also shown that the areas of work life (workload, control, community, rewards, fairness, values) are predictors of occupational burnout among the respondents. This article shows how important the problem of burnout among operating theater medical staff is. Perhaps it will allow nurses and doctors to recognize this syndrome and encourage them make changes to their work to prevent burnout.

Bibliometric Study of Scientific Productivity on the Impacts on Mental Health in Times of Pandemic

Background and Objectives: The presence of the new SARS-CoV-2 virus is causing enormous threats to people’s health and lives, so quantifying the scientific productivity on mental health in times of pandemic is an urgent need, especially to expand the degree of knowledge on mental health problems in regions of low scientific productivity. The aim was to characterize the bibliometric indicators of scientific productivity on mental health during the pandemic in the PubMed Identifier database of the National Library of Medicine in the United States. Materials and Methods: A documentary study (bibliometric) of the scientific productivity on mental health in times of pandemic from January 2020 to June 2021 was carried out. The PubMed database was used to abstract the information from the original scientific articles. The data abstracted were: authors, year of publication, journal name, country, and language of publication. Results: We identified 47 original articles worldwide, which were published in 29 journals and in three languages (English, Spanish, and German). We observed three groups of countries that published on mental health topics. The first group comprised the largest number of publications, which were multicenter studies (six studies), followed by India (five studies), and Italy (four studies). A second group comprised Bangladesh, China, USA, and Spain, with 3 studies each; and a third group comprised 13 countries (Albania, Saudi Arabia, Argentina, Brazil, South Korea, Denmark, Ecuador, Egypt, Greece, Japan, Jordan, Kuwait, and New Zealand) with one study each. Conclusions: Bibliometric indicators of scientific productivity on mental health during the COVID-19 pandemic have ostensibly increased. We verified 47 studies in PubMed, which could serve to improve the understanding and management of COVID-19, as well as serve as a thought-provoking means for other countries and researchers to publish on the state of mental health during and post pandemic.

Neonatal Intra-Ventricular-Hemorrhage Prevention in Premature at < 30 Weeks Gestational Age

Introduction: Intraventricular Hemorrhage (IVH) is a devastating condition mostly in preterm infants at &lt; 30 weeks GA with large morbidities and mortality usually in the first 72 hours after birth. Prevention seems to be the only way to completely deal with this problem. The IVH prevention in this age group has been studied and includes some strategies such as prenatal corticosteroids, cesarean delivery, careful extraction among others, but still, it has an unacceptably high incidence in this population.Objective: To measure the application of a quality improvement project develop from the "Drive to Zero IVH Prevention Project" presented in a Epiclatino lecture in our unit.Material and method: We design a before and after observational study and measured the incidence of IVH before and after October 2017 when a minimum manipulation protocol was implemented at the Cl&iacute;nica del Country (CDC) unit. We also compare these findings to those of other units in the EpicLatino network. All patients born &lt;30 weeks GA with less than 2 days of age, who survived at least 3 days, and had a neuroimaging taken were included. We compared demographics, diagnosis, and frequency of IVH cases, before Nov 2017 and after from CDC and the from 2018-2019 EpicLatino registry using a bivariate analysis. Results: We collected data from 46 cases before, 40 after implementation, and 203 cases from the EpicLatino registry. Demographic characteristics were very similar in the post-intervention with few statistically significant differences in antenatal steroid use (97.5% post, 96% before and 79.3% Epilatino, p=0.016), prolonged rupture of membranes (15% post, 4% before and 15% EpicLatino, p &lt;0.001), vaginal deliveries (7.5% post, 10.9% before and 24.1% Epilatino, p=0.01), suspended chorioamnionitis (12.5% post, 6% before and 20.2% Epiclatino). We found a significant reduction in IVH after the protocol was implemented with only 5 (7.5%) cases post-intervention compared to 19 (29.4%) case before, and when compared to the 81 (39.1%) cases in the registry, p&lt; 0.001. Most of the cases that occurred in the post-intervention occurred before admission to the unit due to obstetric trauma.Discussion: If a well-controlled delivery minimizing obstetric trauma is achieved, a minimal manipulation protocol appears to significantly decrease the incidence of HIV. Controlled, multicenter studies are still required to confirm these findings.

Double-hit lymphoma: optimizing therapy

Aggressive B-cell lymphoma is a heterogeneous entity with disparate outcomes based on clinical and pathological characteristics. While most tumors in this category are diffuse large B-cell lymphoma (DLBCL), the recognition that some cases have high-grade morphology and frequently harbor MYC and BCL2 and/or BCL6 translocations has led to their separate categorization. These cases are now considered distinct from DLBCL and are named “high-grade B-cell lymphoma” (HGBL). Most are characterized by distinct rearrangements, but others have high-grade morphological features without these and are called HGBL-not otherwise specified. Studies have demonstrated that this group of diseases leads to poor outcomes following standard rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone therapy; retrospective and recent single-arm, multicenter studies suggest they should be approached with dose-intense treatment platforms. As yet, this has not been validated in randomized trial settings due to the rarity of these diseases. In the relapsed and refractory setting, novel approaches such as anti-CD19 chimeric antigen receptor T cells and antibodies against CD19 have demonstrated high efficacy in this subgroup. Recently, genomic studies have made much progress in investigating some of the molecular underpinnings that drive their lymphomagenesis and have paved the way for testing additional novel approaches.

Contemporary Neuroprotection Strategies during Cardiac Surgery: State of the Art Review

Open-heart surgery is the leading cause of neuronal injury in the perioperative state, with some patients complicating with cerebrovascular accidents and delirium. Neurological fallout places an immense burden on the psychological well-being of the person affected, their family, and the healthcare system. Several randomised control trials (RCTs) have attempted to identify therapeutic and interventional strategies that reduce the morbidity and mortality rate in patients that experience perioperative neurological complications. However, there is still no consensus on the best strategy that yields improved patient outcomes, such that standardised neuroprotection protocols do not exist in a significant number of anaesthesia departments. This review aims to discuss contemporary evidence for preventing and managing risk factors for neuronal injury, mechanisms of injury, and neuroprotection interventions that lead to improved patient outcomes. Furthermore, a summary of existing RCTs and large observational studies are examined to determine which strategies are supported by science and which lack definitive evidence. We have established that the overall evidence for pharmacological neuroprotection is weak. Most neuroprotective strategies are based on animal studies, which cannot be fully extrapolated to the human population, and there is still no consensus on the optimal neuroprotective strategies for patients undergoing cardiac surgery. Large multicenter studies using universal standardised neurological fallout definitions are still required to evaluate the beneficial effects of the existing neuroprotective techniques.