Analysis of Laboratory Critical Values During COVID-19 Pandemic at Tertiary Hospital in Saudi Arabia.

Purpose: One of the most important aspects of post-analytical laboratory activity is the notification of critical results. Therefore, the aim of this study was to illustrate and analyze the prevalence of critical result values of our clinical laboratory investigations during the pandemic stages of coronavirus-19 (COVID-19) and other research pre-pandemic stages. Methods: The seven-month study was conducted between May 2020 and November 2020. Laboratory data of critical results were collected in this retrospective cohort. Results: In total, 221,384 routine tests and 84,451 STAT tests were performed in our clinical laboratory. Of the 3183 (1.44%) tests result was identified as having Critical values, consisting of 2220 (69.74%) and 963 (30.25%) tests in biochemistry and hematology assays. Among the tests with critical values, 39.6% of which were from emergency department (ED) as STAT testing (1262) and 60.3% (1921) as TAT testing. Testing was found in routine inpatients and outpatients, 58% and 2.3%, respectively, and the most frequent parameter notified was sodium. Conclusion: In our practice, we observed that the higher level of frequency of critical values results is related to inpatients, contradicting several researchers reporting that the higher percentages of critical values were from ED.

A Case of Chronic Lymphocytic Leukemia Coinciding With COVID-19.

Comorbidities including leukemia are risk factors in coronavirus disease 2019 (COVID-19) patients for high morbidity and mortality. The severity of the disease is usually correlated with lymphopenia. On the other hand, we came across a case of marked absolute lymphocytosis in a COVID-19 patient, which further escalated five-fold during his hospital stay. Subsequently, the diagnosis of chronic lymphocytic leukemia (CLL) was made following positive cell surface markers for CD19+, CD5+, and CD20+ (dim), in the presence of restricted immunoglobulin light chain of lambda type on flow cytometry. Numerous cases are available in the literature of COVID-19 among established CLL patients. However, we are mentioning here the second case where the diagnosis of CLL was established accidentally during the work-up for lymphocytosis in COVID-19 infection.

Cathine and cathinone disposition kinetics and neurotransmitter profile in several organs of rats exposed to a single dose of Catha edulis (Vahl) Forssk. ex Endl. extract.

OBJECTIVES: Catha edulis (Vahl) Forssk. ex Endl. (Khat) is a stimulant plant that contains cathine and cathinone, which its abuses induce euphoria, alertness, and motor activity. Since the toxicokinetics of these substances remain unclear, this study was carried out to investigate the disposition kinetics of cathine and cathinone, the neurotransmitter profile, following a single dose of C. edulis extract in rats. METHODS: Twenty-four adult male Wistar albino rats (250-300 g) were randomly selected and divided into six groups of four rats each. All groups received a single oral dose of 2,000 mg/kg body weight, and blood and tissue samples from the brain, lung, heart, liver, and kidney were obtained at intervals of 0.5, 1, 2.5, 5, 12, and 24 h. The cathine and cathinone concentrations were identified and quantified using ion trap ultra-high performance liquid chromatography (HPLC-IT/MS). The neurotransmitter profile was detected using the quadrupole time of flight UPLC-QTOF/MS method. RESULTS: The lung, liver, and heart tissues attained the highest levels of cathine, while the highest level of cathinone was determined in the heart. Cathine and cathinone concentrations in the blood and heart peaked at 0.5 h. The concentrations peaked in the brain 2.5 h later, indicating that the heart had an immediate effect, whereas the brain had a longer-lasting one. They have longer half-lives (2.68 and 5.07 h, respectively) and may remain in the brain for longer durations (3.31 and 2.31 h, respectively). The neurotransmitters epinephrine, dopamine, norepinephrine, and serotonin were detected in a delayed, prolonged and organ-specific manner. CONCLUSIONS: Cathine and cathinone were deposited in considerable concentrations in all tissues analyzed, with the highest Cmax in the lung and Tmax in the heart tissues but not in the brain. In addition, neurotransmitters such as adrenaline, dopamine, norepinephrine, and serotonin were differentially detected in all tested samples in a organ-specific fashion. More study is needed to identify cathine and cathinone's effects on neurotransmitter profiles. Nevertheless, these findings provided a further basis for experimental, clinical, and forensic investigations.

HSP70 Expression Signature in Renal Cell Carcinoma: A Clinical and Bioinformatic Analysis Approach.

Heat shock proteins (HSPs) are cytoprotective against stressful conditions, as in the case of cancer cell metabolism. Scientists proposed that HSP70 might be implicated in increased cancer cell survival. This study aimed to investigate the HSP70 (HSPA4) gene expression signature in patients with renal cell carcinoma (RCC) in correlation to cancer subtype, stage, grade, and recurrence, combining both clinicopathological and in silico analysis approaches. One hundred and thirty archived formalin-fixed paraffin-embedded samples, including 65 RCC tissue specimens and their paired non-cancerous tissues, were included in the study. Total RNA was extracted from each sample and analyzed using TaqMan quantitative Real-Time Polymerase Chain Reaction. Correlation and validation to the available clinicopathological data and results were executed. Upregulated HSP70 (HSPA4) gene expression was evident in RCC compared to non-cancer tissues in the studied cohort and was validated by in silico analysis. Furthermore, HSP70 expression levels showed significant positive correlations with cancer size, grade, and capsule infiltration, as well as recurrence in RCC patients. The expression levels negatively correlated with the overall survival (r = -0.87, p < 0.001). Kaplan-Meier curves showed lower survival rates in high HSP70 expressor group compared to the low expressors. In conclusion, the HSP70 expression levels are associated with poor RCC prognosis in terms of advanced grade, capsule infiltration, recurrence, and short survival.

Diagnostic and Prognostic Risk Assessment of Heat Shock Protein HSPA1B rs2763979 Gene Variant in Asthma.

Given the significant role the heat shock protein Hsp70 plays in modulating cellular homeostasis in several chronic inflammatory disorders, the genetic variation of the inducible HSP70 (HSPA1B) gene may impact protein expression and disease phenotype. The HSPA1B rs2763979 variant has been associated with multiple inflammatory scenarios, but no previous studies have explored its association with asthma. In this sense, this cross-sectional study enrolled 90 children with asthma and 218 age-/sex-matched healthy volunteers for rs2763979 variant genotyping by TaqMan allelic discrimination analysis. The results were investigated under several genetic models and associated with disease susceptibility and clinicolaboratory data. Overall analysis, including the 308 participants, revealed a higher C allele frequency among patients relative to controls (43.0% vs. 33%, p = 0.006). Furthermore, patients with the C variant initially had a higher risk of asthma under heterozygous (OR = 2.75, 95%CI = 1.46-5.18, p = 0.003), homozygous (OR = 3.35, 95%CI = 1.19-9.39, p = 0.008), dominant (OR = 2.83, 95%CI = 1.52-5.25, p < 0.001), and overdominant (OR = 2.12, 95%CI = 1.20-3.74, p = 0.008) models. However, after employing a 1:1 nearest propensity matching analysis, the studied variant showed only borderline significance with asthma under the dominant model in 71 matched cohorts. Interestingly, patients who carry the rs2763979 CC genotype showed favorable spirometric parameters in terms of better (mean ± SD) forced vital capacity (86.3 ± 7.4 vs. 77.7 ± 6.1 and 75.7 ± 7.2 for CT and TT, respectively, p = 0.021), forced expiratory volume in one second before bronchodilation (60.7 ± 12.9 vs. 54.9 ± 7.6 and 56.1 ± 7.5 for CT and TT, respectively, p = 0.021), and an improvement in peak expiratory flow rate after inhaled salbutamol bronchodilator (p = 0.044) relative to the counterpart genotypes. In conclusion, the HSPA1B rs2763979 variant might have prognostic utility as a genetic marker for asthma in our population. Further larger studies on different ethnicities are recommended to validate the results.

Routine laboratory parameters predict serious outcome as well as length of hospital stay in COVID-19.

OBJECTIVES: To validate C-reactive protein (CRP), red cell distribution width (RDW), and neutrophil lymphocyte ratio (NLR) for both serious outcomes and length of hospital stay (LOS) among hospitalized coronavirus disease-19 (COVID-19) patients. METHODS: Laboratory data of adult COVID-19 patients (n=74) was collected in this retrospective cohort. Logistic regression was employed for risk factor evaluation and receiver operating curve was used for comparison of these risk factors for the prediction of serious outcome. Multiple regression was applied to determine the association between routine analytes and LOS. RESULTS: Higher levels of CRP (3 times), white blood cells (20%), and neutrophil counts (40%) were seen in the serious category. Odds ratio for CRP for the serious outcome was 1.052 (p=0.007) and RDW for the serious outcome was 1.218 (p=0.040) in unadjusted model and odds ratio for CRP for the serious outcome was 1.048 (p=0.024) and for RDW 1.286 (p=0.023) in adjusted model. In a multivariate regression analysis for the LOS of the unadjusted models consisting of NLR, monocyte lymphocyte ratio (MLR) and platelet lymphocyte ratio (PLR), the beta coefficients (BC) for the CRP were 0.006 (NLR), 0.005 (MLR) and 0.006 (PLR), whereas -0.029 (NLR), -0.034 (MLR) and -0.027 (PLR) were BCs for mean corpuscular hemoglobin concentration (MCHC). Additionally, in adjusted models, the BCs for MCHC were -0.044 (NLR), -0.047 (MLR) and -0.043 (PLR). However, the CRP was consistent with 0.004 (BC) in all models. CONCLUSION: We observed that CRP is a better predictor than RDW and NLR for serious outcome among COVID-19 patients. Besides, CRP was positively, whereas MCHC was negatively associated with LOS.

Molecular basis of immunoglobulin heavy constant G4 gene (IGHG4)-related low serum IgG4 subclasses in Down syndrome.

OBJECTIVES: To investigate the molecular mechanism of low serum IgG4 at the level of the immunoglobulin heavy constant G4 gene (IGHG4). Patients with Down syndrome (DS) are more likely to exhibit immunological abnormalities that predispose them to infection. Among other anomalies, individuals with DS have altered serum concentrations of some subclasses of immunoglobulin G (IgG), particularly the IgG4 subclasses. METHODS: In this prospective study, quantitative real-time polymerase chain reaction (qPCR) was carried out from December 2017 to June 2019 in the University Hospital of Saint-Etienne, Saint-Etienne, France to measure the number of IGHG4 copies and to compare those outcomes with a reference gene (36B4). An IGHG4/36B4 ratio was considered normal when between 0.8 and 1.2. Forty-four DS patients, comprising 23 DS patients carrying severe low serum IgG4 and 21 DS patients with normal serum IgG4 (level >0.1 g/L). The patient group was compared with 38 healthy donors (controls) without DS. RESULTS: The heavy chain gene IGHG4 heterozygous deletion was found in 16 (69.57%) DS patients with low serum IgG4 versus in 2 (9.52%) DS with normal serum IgG4 (p=0.0001). In the control group, deletion was found in 5.26% (2/38) of the sample. CONCLUSION: The heavy chain gene IGHG4 haploinsufficiency is highly correlated with low serum IgG4 in our population with DS, but other relevant factors must be assessed in future work.

Prevalence of primary anti-tuberculosis drug resistance at the tertiary center in Saudi Arabia and associated risk factors.

OBJECTIVES: To estimate the prevalence mono-resistant tuberculosis (MR-TB) and multidrug resistant TB (MDR-TB), and evaluate the risk factors associated with the drug-resistant tuberculosis (DR-TB). METHODS: A descriptive, retrospective study was applied, utilizing the TB patients' medical records at King Fahd Armed Forces Hospital (KFAFH), Jeddah, Saudi Arabia. The records of patients notified between 2000 and 2018 were reviewed and culture positive cases for Mycobacterium tuberculosis species were included. Moreover, the risk factors included were age, gender, smoking history, renal disease, liver disease, hyperbilirubinemia, diabetes mellitus, and human immunodeficiency virus (HIV). RESULTS: Nine hundred and one cases in entirety were involved in the research, out of which 193 had drug-resistant tuberculosis (DR-TB) (21.4%). Out of the 21.4% DR-TB, 91.7% were MR-TB and 8.3% were MDR-TB. The highest MR prevalence was for pyrazinamide at 33.4%, while the lowest resistance was for ethambutol at 7.1%. For the risk factors of drug-resistant TB, only age depicted a statistically significant (p<0.01) but weak negative (r= -0.145) correlation with anti-TB drug resistance. CONCLUSION: Rates of DR-TB reported in the study are considered higher compared to the recently reported national and international rates. According to the results, only younger people are at risk of developing DR-TB. Moreover, genetic mutation may play a role in drug resistance among our cases specifically for pyrazinamide monoresistance.