Effect of geographical factors on reference values of creatine kinase isoenzyme.

The aim of this study was to investigate the geographical spatial distribution of creatine kinase isoenzyme (CK-MB) in order to provide a scientific basis for clinical examination. The reference values of CK-MB of 8697 healthy adults in 137 cities in China were collected by reading a large number of literates. Moran index was used to determine the spatial relationship, and 24 factors were selected, which belonged to terrain, climate, and soil indexes. Correlation analysis was conducted between CK-MB and geographical factors to determine significance, and 9 significance factors were extracted. Based on R language to evaluate the degree of multicollinearity of the model, CK-MB Ridge model, Lasso model, and PCA model were established, through calculating the relative error to choose the best model PCA, testing the normality of the predicted values, and choosing the disjunctive kriging interpolation to make the geographical distribution. The results show that CK-MB reference values of healthy adults were generally correlated with latitude, annual sunshine duration, annual mean relative humidity, annual precipitation amount, and annual range of air temperature and significantly correlated with annual mean air temperature, topsoil gravel content, topsoil cation exchange capacity in clay, and topsoil cation exchange capacity in silt. The geospatial distribution map shows that on the whole, it is higher in the north and lower in the south, and gradually increases from the southeast coastal area to the northwest inland area. If the geographical factors are obtained in a location, the CK-MB model can be used to predict the CK-MB of healthy adults in the region, which provides a reference for us to consider regional differences in clinical diagnosis.

General population reference values for the Functional Assessment of Cancer Therapy-Lung and PROMIS-29.

BACKGROUND: Therapeutic advances in lung cancer have turned attention toward patient-reported outcome measures (PROMs) as important clinical outcomes. The Functional Assessment of Cancer Therapy-Lung (FACT-L) is a common endpoint in lung cancer trials. This study calculated FACT-L reference values for the United States (US) general population. METHODS: Adults from the US general population (N = 2001) were surveyed between September 2020 and November 2020. Surveys contained 126 questions, including the FACT-L [36 items; FACT-G and four subscales (Physical Well-Being [PWB], Social Well-Being [SWB], Emotional Well-Being [EWB], and Functional Well-Being [FWB]) and the Lung Cancer Subscale (LCS), and a Trial Outcome Index (TOI)]. Reference values for each FACT-L scale were calculated with means for the total sample and separately for participants with: no comorbidities, COVID-19 as only comorbidity, no COVID-19. RESULTS: In the total sample, the reference scores were as follows: PWB = 23.1; SWB = 16.8; EWB = 18.5; FWB = 17.6; FACT-G = 76.0; LCS = 23.0, TOI = 63.7, and FACT-L Total = 99.0. Scores were lower for those reporting a prior diagnosis of COVID-19, especially for SWB (15.7) and FWB (15.3). SWB scores were lower than previous references values. CONCLUSIONS: These data provide US general adult population reference value set for FACT-L. While some of the subscale results were lower than those found in the reference data for other PROMs, these data were obtained in a more contemporaneous time frame juxtaposed with the COVID-19 pandemic and may represent a new peri-pandemic norm. Thus, these reference values will be useful for future clinical research.

Establishment of reference intervals for complete blood count in times of COVID-19 and vaccination.

Introduction: COVID-19 and vaccination may affect some parameters of the complete blood count (CBC). The aim of this study was to determine reference intervals (RI) of CBC in healthy population with different COVID-19 and vaccination backgrounds and compare them with those established previously. Materials and methods: A cross-sectional study was conducted in donors who attended the Traumatology Hospital "Dr. Victorio de la Fuente Narváez" (HTVFN) from June to September 2021. Reference intervals were established using the non-parametric method on Sysmex XN-1000. For differences between groups with different COVID-19 and vaccination backgrounds, non-parametric tests were used. Results: The RI were established in 156 men and 128 women. Haemoglobin (Hb), haematocrit (Hct), red blood cells (RBC), platelets (Plt), mean platelets volume (MPV), monocytes and relative neutrophils were higher in men than women (P < 0.001). The percentiles of Hb, Hct, RBC, MPV and relative monocytes showed higher values; Plt, white blood cells (WBC), lymphocytes, monocytes, neutrophils, eosinophils and absolute basophils, the 2.5th was higher and the 97.5th was lower; for lymphocytes and relative neutrophils, both percentiles had a trend toward lower values, compared to previous RI. Differences between groups with different COVID-19 and vaccination backgrounds, in lymphocytes (P = 0.038), neutrophils (P = 0.017) and eosinophils (P = 0.018) in men; Hct (P = 0.014), RDW (P = 0.023) in women and MPV (P = 0.001) in both, were not considered pathological. Conclusions: The RI for the CBC were established in a Mestizo-Mexican population with different COVID-19 and vaccination backgrounds, so should be updated and validated in different hospitals close to the HTVFN that use the same analyser.

The application of a surgical face mask over different oxygen delivery devices; a crossover study of measured end-tidal oxygen concentrations.

BACKGROUND: The application of a surgical face mask over oxygen delivery devices is now a widespread recommendation in the setting of the Coronavirus disease pandemic. This addition is designed to reduce droplet spread, but this also changes the nature of these devices, and may alter the amount of oxygen delivered to a patient. This research investigated how placing a surgical face mask over both a simple plastic mask ("Hudson mask") and nasal cannula altered the concentration of available oxygen measured at the nares. METHODS: We measured the inspired and end-tidal oxygen concentrations of five healthy non-smoking volunteers. Oxygen was delivered via nasal cannula and also a simple plastic face mask, at flow rates of 2, 4, 6 and 8 l per minute, with and without an overlying surgical face mask. RESULTS: Adding a surgical mask over nasal cannula caused an appreciable rise in the end-tidal oxygen concentrations at all the measured oxygen flow rates 2, 4, 6, 8 L/minute. With the Hudson mask, there was a rise in oxygen concentration at 4 and 6 L/minute. For example, at a flow rate of 4 l/min via nasal cannula, available oxygen concentration increased from 24 to 36%, and via the Hudson mask the concentration rose from 27 to 38%. CONCLUSIONS: The addition of a surgical face mask over both nasal cannula and a Hudson mask resulted in an increased available oxygen concentration. This may be valuable where more advanced oxygen devices are not available, or alternatively providing adequate supplemental oxygen at lower flow rates and thus making critical savings in oxygen usage.

Rapid screening and identification of viral pathogens in metagenomic data.

BACKGROUND: Virus screening and viral genome reconstruction are urgent and crucial for the rapid identification of viral pathogens, i.e., tracing the source and understanding the pathogenesis when a viral outbreak occurs. Next-generation sequencing (NGS) provides an efficient and unbiased way to identify viral pathogens in host-associated and environmental samples without prior knowledge. Despite the availability of software, data analysis still requires human operations. A mature pipeline is urgently needed when thousands of viral pathogen and viral genome reconstruction samples need to be rapidly identified. RESULTS: In this paper, we present a rapid and accurate workflow to screen metagenomics sequencing data for viral pathogens and other compositions, as well as enable a reference-based assembler to reconstruct viral genomes. Moreover, we tested our workflow on several metagenomics datasets, including a SARS-CoV-2 patient sample with NGS data, pangolins tissues with NGS data, Middle East Respiratory Syndrome (MERS)-infected cells with NGS data, etc. Our workflow demonstrated high accuracy and efficiency when identifying target viruses from large scale NGS metagenomics data. Our workflow was flexible when working with a broad range of NGS datasets from small (kb) to large (100 Gb). This took from a few minutes to a few hours to complete each task. At the same time, our workflow automatically generates reports that incorporate visualized feedback (e.g., metagenomics data quality statistics, host and viral sequence compositions, details about each of the identified viral pathogens and their coverages, and reassembled viral pathogen sequences based on their closest references). CONCLUSIONS: Overall, our system enabled the rapid screening and identification of viral pathogens from metagenomics data, providing an important piece to support viral pathogen research during a pandemic. The visualized report contains information from raw sequence quality to a reconstructed viral sequence, which allows non-professional people to screen their samples for viruses by themselves (Additional file 1).

A Less Restrictive Policy for Liver Transplantation in Coronavirus Disease 2019 Positive Patients, Based Upon Cycle Threshold Values.

Coronavirus disease 2019 drastically impacted solid organ transplantation. Lacking scientific evidence, a very stringent but safer policy was imposed on liver transplantation (LT) early in the pandemic. Restrictive transplant guidelines must be reevaluated and adjusted as data become available. Before LT, the prevailing policy requires a negative severe acute respiratory syndrome coronavirus 2 real-time polymerase chain reaction (RT-PCR) of donors and recipients. Unfortunately, prolonged viral RNA shedding frequently hinders transplantation. Recent data reveal that positive test results for viral genome are frequently due to noninfectious and prolonged convalescent shedding of viral genome. Moreover, studies demonstrated that the cycle threshold of quantitative RT-PCR could be leveraged to inform clinical transplant decision-making. We present an evidence-adjusted and significantly less restrictive policy for LT, where risk tolerance is tiered to recipient acuity. In addition, we delineate the pretransplant clinical decision-making, intra- and postoperative management, and early outcome of 2 recipients of a liver graft performed while their RT-PCR of airway swabs remained positive. Convalescent positive RT-PCR results are common in the transplant arena, and the proposed policy permits reasonably safe LT in many circumstances.

Myocardial deformation assessed by CMR in children after multisystem inflammatory syndrome (MIS-C).

BACKGROUND: Short-term sequelae of Multisystem Inflammatory Syndrome in Children (MIS-C), recently published by our institution, showed rapid improvement of the cardiac abnormalities within a few weeks after the onset of the disease. However, subtle residual abnormalities, affecting mainly the myocardial interstitium, were shown in some of the patients. The current study aimed to assess myocardial deformation with CMR shortly after MIS-C. METHODS: Sixty children were included into the study; 30 following MIS-C (onset-to-scan mean 27 days, SD 11) and 30 controls. Strain values were compared between patients and controls and additionally to published paediatric normal CMR values. U-Mann Whitney test was used for comparison of the myocardial deformation between patients and controls. RESULTS: Median age of the patients was 9.0 years (range 0.99-14.4) and controls 9.8 years (range 4.7-14.9). All conventional CMR parameters in patients were in normal range. Strain values were significantly lower in patients than in controls. When compared to published centile graphs, radial and circumferential global strain was within 2.5th and 97.5th centile in all patients. Eleven patients had global longitudinal strain between 2.5th centile and 50th centile, 1 patient was below 2.5th centile and all the others above 50th centile. Only 3 controls had global longitudinal strain between 2.5th centile and 50th centile, all other had higher strain. CONCLUSIONS: This study demonstrates that myocardial deformation indices measured by CMR are within normal range in the vast majority of the patients within a few weeks after the onset of MIS-C. However, when compared to healthy controls, all strain parameters were lower in patients.

Severe Acute Respiratory Syndrome Coronavirus 2 Total and Subgenomic RNA Viral Load in Hospitalized Patients.

BACKGROUND: Previous studies demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be detected for weeks after infection. The significance of this finding is unclear and, in most patients, does not represent active infection. Detection of subgenomic RNA has been proposed to represent productive infection and may be a useful marker for monitoring infectivity. METHODS: We used quantitative reverse-transcription polymerase chain reaction (RT-qPCR) to quantify total and subgenomic nucleocapsid (sgN) and envelope (sgE) transcripts in 185 SARS-CoV-2-positive nasopharyngeal swab samples collected on hospital admission and to relate to symptom duration. RESULTS: We find that all transcripts decline at the same rate; however, sgE becomes undetectable before other transcripts. The median duration of symptoms to a negative test is 14 days for sgE and 25 days for sgN. There is a linear decline in subgenomic compared to total RNA, suggesting that subgenomic transcript copy number is dependent on copy number of total transcripts. The mean difference between total and sgN is 16-fold and the mean difference between total and sgE is 137-fold. This relationship is constant over duration of symptoms, allowing prediction of subgenomic copy number from total copy number. CONCLUSIONS: Subgenomic RNA may be no more useful in determining infectivity than a copy number threshold determined for total RNA.

Relationship of magnesemia with myocardial damage and mortality in patients with COVID-19.

Magnesium (Mg) is the second most abundant intracellular cation and plays a significant role in immune system and cardiac protection. Mg deficiency contributes to chronic low-grade inflammation leading to cardiovascular diseases, and low Mg level exacerbates virus-induced inflammation. The aim of the study was to investigate whether serum magnesium level is associated with myocardial damage and prognosis of COVID-19. This was a single-center, observational retrospective study of patients with COVID-19. The study population was divided into two groups according to in-hospital mortality: a survivor group (SG) and a non-survivor group (NSG). Myocardial damage was defined as blood levels of cardiac troponin I (cTnI) above the 99th percentile upper reference limit. Magnesium, variables regarding inflammation, and myocardial damage were compared between the groups. A total of 629 patients with COVID-19 were included. Mortality rate was 11.85% (n = 82). There were 61 (74.4%) and 294 male patients (53.7%) in NSG and SG, respectively (p = 0.001). The median age of NSG was 64.5 years (min-max: 37-93) and the median age of SG was 56.0 years (min-max: 22-92) (p < 0.001). Median serum magnesium levels of NSG and SG were 1.94 mg/dL (min-max: 1.04-2.87) and 2.03 mg/dL (min-max: 1.18-2.88), respectively (p = 0.027). Median cTnI levels of NSG and SG were 25.20 pg/mL (min-max: 2.10-2240.80) and 4.50 pg/mL (min-max: 0.50-984.3), respectively (p < 0.001). The cTnI levels were lower in those patients whose serum Mg levels were higher than 1.94. Although serum magnesium level was not a predictor for in-hospital mortality, there was a significant negative correlation between magnesemia and myocardial damage.

Serum magnesium: time for a standardized and evidence-based reference range.

Magnesium deficiency can have serious health consequences. Low magnesium intake or low serum levels are risk factors for e.g. type 2 diabetes and cardiovascular diseases. Despite its scientifically recognized importance, too little attention is paid to magnesium in clinical practice. This may be due to the fact that there is no uniform and evidence-based reference range for serum magnesium as is the case for other electrolytes such as sodium and potassium. The serum magnesium concentration is also of a limited informative value, as it is maintained for a long time by releasing magnesium from body pools. A low serum magnesium is a definite sign of magnesium deficiency; however, values within the reference range do not rule out deficiencies. Nevertheless, serum magnesium should become part of routine diagnostics in order to be able to better detect deficiency states. For serum magnesium, a reference range of 0.75 to 0.95 mmol/L (1.82 to 2.31 mg/dL) can often be found. However, according to the current data situation, serum magnesium values of less than 0.85 mmol/L are associated with increased health risks. Therefore, the lower limit of the reference range should be raised to 0.85 mmol/L (2.07 mg/dL).

Distribution and reference interval establishment of neutral-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in Chinese healthy adults.

BACKGROUND: Neutral-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) are associated with coronavirus disease 2019 (COVID-19) and many diseases, but there are few data about the reference interval (RI) of NLR, LMR, and PLR. METHODS: The neutrophil count, lymphocyte count, monocyte count, and platelet count of 404,272 Chinese healthy adults (>18 years old) were measured by Sysmex XE-2100 automatic hematology analyzer, and NLR, LMR, and PLR were calculated. According to CLSI C28-A3, the nonparametric 95% percentile interval is defined as the reference interval. RESULTS: The results of Mann-Whitney U test showed that NLR (p < .001) in male was significantly higher than that in female; LMR (p < .001) and PLR (p < .001) in male were significantly lower than that in female. Kruskal-Wallis H test showed that there were significant differences in NLR, LMR, and PLR among different genders and age groups (p < .001). The linear graph showed that the reference upper limit of NLR and PLR increased with age and the reference upper limit of LMR decreases with age in male population. In female population, the reference upper limit of NLR in 50-59 group, LMR in >80 group, and PLR in 70-79 group appeared a trough; the reference upper limit of NLR in >80 group, LMR in 50-59 group, and PLR in 40-49 group appeared peak. CONCLUSION: The establishment of RI for NLR, LMR, and PLR in Chinese healthy adults according to gender and age will promote the standardization of clinical application.

E-cigarette-induced pulmonary inflammation and dysregulated repair are mediated by nAChR α7 receptor: role of nAChR α7 in SARS-CoV-2 Covid-19 ACE2 receptor regulation.

Electronic cigarette (e-cig) vaping is increasing rapidly in the United States, as e-cigs are considered less harmful than combustible cigarettes. However, limited research has been conducted to understand the possible mechanisms that mediate toxicity and pulmonary health effects of e-cigs. We hypothesized that sub-chronic e-cig exposure induces inflammatory response and dysregulated repair/extracellular matrix (ECM) remodeling, which occur through the α7 nicotinic acetylcholine receptor (nAChRα7). Adult wild-type (WT), nAChRα7 knockout (KO), and lung epithelial cell-specific KO (nAChRα7 CreCC10) mice were exposed to e-cig aerosol containing propylene glycol (PG) with or without nicotine. Bronchoalveolar lavage fluids (BALF) and lung tissues were collected to determine e-cig induced inflammatory response and ECM remodeling, respectively. Sub-chronic e-cig exposure with nicotine increased inflammatory cellular influx of macrophages and T-lymphocytes including increased pro-inflammatory cytokines in BALF and increased SARS-Cov-2 Covid-19 ACE2 receptor, whereas nAChRα7 KO mice show reduced inflammatory responses associated with decreased ACE2 receptor. Interestingly, matrix metalloproteinases (MMPs), such as MMP2, MMP8 and MMP9, were altered both at the protein and mRNA transcript levels in female and male KO mice, but WT mice exposed to PG alone showed a sex-dependent phenotype. Moreover, MMP12 was increased significantly in male mice exposed to PG with or without nicotine in a nAChRα7-dependent manner. Additionally, sub-chronic e-cig exposure with or without nicotine altered the abundance of ECM proteins, such as collagen and fibronectin, significantly in a sex-dependent manner, but without the direct role of nAChRα7 gene. Overall, sub-chronic e-cig exposure with or without nicotine affected lung inflammation and repair responses/ECM remodeling, which were mediated by nAChRα7 in a sex-dependent manner.

Analytical and Clinical Performance of Droplet Digital PCR in the Detection and Quantification of SARS-CoV-2.

BACKGROUND AND OBJECTIVE: Since the initial coronavirus disease outbreak in late 2019 (COVID-19), reverse-transcription real-time polymerase chain reaction (RT-qPCR) has become the gold standard test to detect severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). However, a more sensitive and accurate diagnostic tool was required. Therefore, droplet digital polymerase chain reaction (ddPCR) was suggested as an alternative method. Here, we evaluated the performance of ddPCR to detect SARS-CoV-2 and compared it to the performance of RT-qPCR. METHODS: The analytical performances, including limit of blank and limit of detection, were established using positive and negative SARS-CoV-2 reference materials. A total of 366 RNA extracts (173 positive and 193 negative by RT-qPCR) were collected from four institutions and tested with a Bio-Rad SARS-CoV-2 ddPCR kit that detects the SARS-CoV-2 genome using primers for N1 and N2. RESULTS: Limit of blank was set at 0, and the limits of detection of N1 and N2 were 1.99 copies/µL and 5.18 copies/µL, respectively. Linearity was evaluated using serial dilution samples, which demonstrated good results (R2: 0.999, linear range: 5.88-6825.25 copies/µL for N1 and R2: 0.999, 5.53-5855.47 copies/µL for N2). The results of ddPCR and RT-qPCR revealed substantial agreement (Cohen's kappa: 0.639, p < 0.01). The 63 samples with positive ddPCR but negative RT-qPCR showed low copy numbers, and 55% of them had COVID-19-related symptoms. CONCLUSIONS: Droplet digital polymerase chain reaction demonstrated excellent sensitivity for SARS-Cov-2 detection and consistently agreed with the results from conventional RT-qPCR. Furthermore, ddPCR provided quantitative data that can be used to monitor changes in the viral load of patients with COVID-19.

Point-of-care faecal calprotectin testing in patients with paediatric inflammatory bowel disease during the COVID-19 pandemic.

OBJECTIVES: Following the disruption of normal paediatric inflammatory bowel disease (IBD) services during the peak of the COVID-19 pandemic, we prospectively audited the first-time use of home faecal calprotectin testing. We aimed to provide an alternative to laboratory tests and to assess the value of home testing as part of our regular services going forward. METHODS: Home test kits as well as accompanying user instructions were made available to our patients with paediatric IBD that required faecal calprotectin test between 17 April and 12 August 2020. Once the user completed the test, results were automatically uploaded to the result portal and clinical staff were alerted. A user feedback questionnaire was sent to users that had completed the home test. RESULTS: Of the 54 patients, 41 (76%) aged between 4.7 and 18.1 years used the home test. A total of 45 home tests were done, one of which produced an invalid result. The decision to modify management was made in 12 (29%) of the patients, while 14 (34%) had no changes made and 15 (37%) required further assessment. Twenty (48.8%) responded to the questionnaire and 85% stated that they preferred the home test to the laboratory testing method. CONCLUSIONS: Home calprotectin tests were useful in guiding clinical management during a time when laboratory testing was less available. They may offer benefits as part of routine paediatric IBD monitoring to help target appointments and reduce unnecessary hospital attendances in the future.

Prognostic performance of troponin in COVID-19: A diagnostic meta-analysis and meta-regression.

BACKGROUND: Cardiac injury is frequently encountered in patients with coronavirus disease 2019 (COVID-19) and is associated with increased risk of mortality. Elevated troponin may signify myocardial damage and is predictive of mortality. This study aimed to assess the prognostic value of troponin above the 99th percentile upper reference limit (URL) for mortality, and factors affecting the relationship. METHODS: A comprehensive literature search of PubMed (MEDLINE), Scopus and Embase was undertaken, from inception of the databases until 16 December 2020. The key exposure was elevated serum troponin, defined as troponin (of any type) above the 99th percentile URL. The outcome was mortality due to any cause. RESULTS: In total, 12,262 patients from 13 studies were included in this systematic review and meta-analysis. The mortality rate was 23% (20-26%). Elevated troponin was observed in 31% (23-38%) of patients. Elevated troponin was associated with increased mortality [odds ratio (OR) 4.75, 95% confidence interval (CI) 4.07-5.53; P < 0.001; I2 = 19.9%]. Meta-regression showed that the association did not vary with age (P = 0.218), male gender (P = 0.707), hypertension (P = 0.182), diabetes (P = 0.906) or coronary artery disease (P = 0864). The association between elevated troponin and mortality had sensitivity of 0.55 (0.44-0.66), specificity of 0.80 (0.71-0.86), positive likelihood ratio of 2.7 (2.2-3.3), negative likelihood ratio of 0.56 (0.49-0.65), diagnosis odds ratio of 5 (4-5) and area under the curve of 0.73 (0.69-0.77). The probability of mortality was 45% in patients with elevated troponin and 14% in patients with non-elevated troponin. CONCLUSION: Elevated troponin was associated with mortality in patients with COVID-19 with 55% sensitivity and 80% specificity.