Comparing Left Ventricular Structure and Functions in End-Stage Renal Disease Using Conventional Echocardiography and 2D Speckle Tracking Echocardiography.

BACKGROUND: Patients on hemodialysis (HD) are prone to various cardiovascular complications. Two-dimensional speckle tracking echocardiography (2D STE) is an innovative technique for early myocardial dysfunction detection, even with normal ejection fraction (EF). OBJECTIVE: We aim to detect left ventricle (LV) dysfunction in regular hemodialysis patients using 2D STE compared to traditional echocardiography. METHODS: The study comprised 30 patients with end-stage renal disease (ESRD), subdivided according to left ventricular mass index (LVMI) into group 1 with left ventricular hypertrophy (LVH) (n=19) and group 2 without LVH (n=11). Another 30 healthy control subjects were recruited as group 3. The EF, average systolic velocity (Sa), and 2D LV strain were taken as measures of LV systolic function. The indicators for diastolic function included the E/A ratio and E velocity/peak early diastolic velocity. RESULTS: Regarding the parameters of LV systolic and diastolic functions assessed by traditional echocardiography, we found no significant difference between groups 1 and 2. However, using 2D STE, we observed significant differences in the average Sa velocity (p=0.025), average LV strain (p=0.03), 2D global longitudinal strain (GLS) (p=0.03), E/Ea (p=0.003), and LV myocardial performance index (MPI) (p=0.006). Also, a significant positive correlation was found between LVMI and left ventricular end-diastolic diameter (LVEDD) (p<0.01, r=0.63), EF measured by 2D (p=0.034, r=0.39), mitral E/A ratio (p=0.03, r=0.49), and mitral E/Ea (p<0.01, r=0.72). There was a significantly strong negative correlation between LVMI and 2D average LV strain (p=0.034, r=-0.39). CONCLUSION: We concluded that 2D STE is more sensitive than a conventional echo in detecting early LV systolic and diastolic dysfunction even in patients with normal EF.

Monocytes subsets altered distribution and dysregulated plasma hsa-miR-21-5p and hsa-miR-155-5p in HCV-linked liver cirrhosis progression to hepatocellular carcinoma.

PURPOSE: The authors aim to investigate the altered monocytes subsets distribution in liver cirrhosis (LC) and subsequent hepatocellular carcinoma (HCC) in association with the expression level of plasma Homo sapiens (has)-miR-21-5p and hsa-miR-155-5p. A step toward non-protein coding (nc) RNA precision medicine based on the immune perturbation manifested as altered monocytes distribution, on top of LC and HCC. METHODS: Seventy-nine patients diagnosed with chronic hepatitis C virus (CHCV) infection with LC were enrolled in the current study. Patients were sub-classified into LC group without HCC (n = 40), LC with HCC (n = 39), and 15 apparently healthy controls. Monocyte subsets frequencies were assessed by flow cytometry. Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p and hsa-miR-155-5p expression. RESULTS: Hsa-miR-21-5p correlated with intermediate monocytes (r = 0.30, p = 0.007), while hsa-miR-155-5p negatively correlated with non-classical monocytes (r = - 0.316, p = 0.005). ROC curve analysis revealed that combining intermediate monocytes frequency and hsa-miR-21 yielded sensitivity = 79.5%, specificity = 75%, and AUC = 0.84. In comparison, AFP yielded a lower sensitivity = 69% and 100% specificity with AUC = 0.85. Logistic regression analysis proved that up-regulation of intermediate monocytes frequency and hsa-miR-21-5p were independent risk factors for LC progression to HCC, after adjustment for co-founders. CONCLUSION: Monocyte subsets differentiation in HCC was linked to hsa-miR-21-5p and hsa-miR-155-5p. Combined up-regulation of intermediate monocytes frequency and hsa-miR-21-5p expression could be considered a sensitive indicator of LC progression to HCC. Circulating intermediate monocytes and hsa-miR-21-5p were independent risk factors for HCC evolution, clinically and in silico proved.

Non-classical monocytes frequency and serum vitamin D3 levels are linked to diabetic foot ulcer associated with peripheral artery disease.

AIMS/INTRODUCTION: Peripheral artery disease (PAD) serves as a risk factor for diabetic foot ulcers (DFUs). PAD pathology involves atherosclerosis and impaired immunity. Non-classical monocytes are believed to have an anti-inflammatory role. 1,25-Dihydroxy vitamin D (vitamin D3 ) is claimed to have immune-modulating and lipid-regulating roles. Vitamin D receptor is expressed on monocytes. We aimed to investigate if circulating non-classical monocytes and vitamin D3 were implicated in DFUs associated with PAD. MATERIALS AND METHODS: There were two groups of DFU patients: group 1 (n = 40) included patients with first-degree DFUs not associated with PAD, and group 2 (n = 50) included patients with DFU with PAD. The monocyte phenotypes were detected using flow cytometry. Vitamin D3 was assessed by enzyme-linked immunosorbent assay. RESULTS: DFU patients with PAD showed a significant reduction in the frequency of non-classical monocytes and vitamin D3 levels, when compared with DFU patients without PAD. The percentage of non-classical monocytes positively correlated with vitamin D3 level (r = 0.4, P < 0.01) and high-density lipoprotein (r = 0.5, P < 0.001), whereas it was negatively correlated with cholesterol (r = -0.5, P < 0.001). Vitamin D3 was negatively correlated with triglyceride/high-density lipoprotein (r = -0.4, P < 0.01). Regression analysis showed that a high vitamin D3 serum level was a protective factor against PAD occurrence. CONCLUSIONS: Non-classical monocytes frequency and vitamin D3 levels were significantly reduced in DFU patients with PAD. Non-classical monocytes frequency was associated with vitamin D3 in DFUs patients, and both parameters were linked to lipid profile. Vitamin D3 upregulation was a risk-reducing factor for PAD occurrence.

Flow cytometry assessment of monocyte subsets alteration in hepatocellular carcinoma post hepatitis C virus infection.

Hepatocellular carcinoma (HCC) is assumed to be an immunogenic malignancy since 90% of cases develop in environments with ongoing inflammation. Monocyte subsets contribute to tumoral immunity. Most HCC patients are discovered at late stages, which lowers their survival chances. We aimed to determine whether altered frequency of monocyte subsets contribute to post hepatitis C virus infection-liver cirrhosis (HCV-LC) development to HCC. This cross-sectional study enrolled 105 patients classified as post HCV-HCC (n=72) and post HCV-LC (n=33) patients. The monocyte subsets frequency was assessed by flow-cytometry. There was a significant increase in intermediate monocytes and decrease in non-classical monocytes in HCC group when compared to the LC group (P = 0.001 and 0.006, respectively). Intermediate monocyte frequency was positively correlated with cholesterol and triglycerides (r = 0.296, P < 0.002 and r = 0.247, P < 0.011, respectively). The receiver operating characteristic (ROC) curve revealed that intermediate monocytes percentage at a cutoff ≥ 0.625% and non-classical monocytes percentage at a cutoff ≤ 0.61% differentiated between patients with HCV-LC and those with HCV-HCC with a sensitivity of 76.4% and 69.4%, respectively, while both revealed low specificity of 51.5%. According to logistic regression analysis, only the triglyceride level was found to be an independent risk factor for HCC development [OR =1.014 (11.001-1.026), P = 0.031]. Finally, we concluded that post-HCV-HCC is characterized by an upregulation of intermediate monocytes and a downregulation of non-classical monocytes when compared to Post-HCV-LC. Intermediate and non-classical monocytes frequency can aid to screening biomarkers for HCC development. Intermediate monocyte frequency may be linked to hyperlipemia. The level of triglycerides is proposed as an independent risk factor for HCC emergence.

Natural Killer Group 2D Receptor and B1a Cells Crosstalk in Post-Hepatitis C Virus Infection Hepatocellular Carcinoma and Cirrhosis.

Background: Natural killer (NK) and B1a cells are implicated in innate immune surveillance against chronic hepatitis C virus (CHCV). NK group 2D (NKG2D) receptor is important for B cell differentiation. This study was designed to assess whether B1a cells and NK Cells expressing NKG2D are implicated in post-hepatitis C infection hepatocellular carcinoma (post-HCV HCC) and cirrhosis using flow cytometry and investigate the association between NK-expressing NKG2D and B1a in complications of CHCV infection. Methods: In this cross-sectional study, 111 participants were included and divided into the post-HCV HCC (n = 50), post-HCV liver cirrhosis (n = 31), and CHCV (n = 30) groups. Results: The percentage of B1a cells (B1a%) and the mean fluorescence intensity (MFI) of NKG2D (NKG2D MFI) showed a significant increase in the CHCV group compared with those in the post-HCV liver cirrhosis and post-HCV HCC groups (P < 0.05). A positive correlation was observed between NKG2D MFI and B1a% (r = 0.6, P < 0.001). The receiver operating characteristic (ROC) curve revealed that NKG2D MFI and B1a% differentiated between patients with CHCV infection and those with HCC with a sensitivity of 92% and 98%, respectively, and differentiated between patients with CHCV infection and those with liver cirrhosis with a sensitivity of 94% and 90%, respectively. Conclusion: Downregulation of B1a frequency and NKG2D intensity is implicated in the progression of CHCV infection to cirrhosis and HCC. NKG2D receptor is associated with the frequency of circulating B1a cells. NKG2D intensity and B1a% can be used as indicators of CHCV progression.

Impact of Systemic Diseases on Olfactory Function in COVID-19 Infected Patients.

Background: COVID-19 (SARS-CoV-2/2019-nCoV) is now a major public health threat to the world. Olfactory dysfunctions (ODs) are considered potential indicating symptoms and early case identification triaging for coronavirus disease 2019 (COVID-19). The most common reported comorbidities are diabetes mellitus, chronic lung disease, and cardiovascular disease. The objective of this study was to evaluate prevalence of different types of smell disorders in patients with laboratory-confirmed COVID-19 infection and impact of involved systemic diseases. Methodology: A cross-sectional retrospective study has been done for patients with laboratory-confirmed COVID-19 infection (mild-to-moderate). The data collected from patient's files and developed online electronic questionnaire (WhatsApp) based on the patients most common and recurrent reported data including: a) symptoms of olfactory dysfunction and associated covid19 symptoms fever and headache, cough, sore throat, pneumonia, nausea, vomiting and diarrhea, arthralgia and myalgia and taste dysfunction. b) Associated systemic diseases including: diabetes, hypertension, asthma, chronic renal disease, chorionic liver disease and hypothyroidism. Results: Of 308 patients confirmed with Covid-19 infection, (72.4%) developed OD distributed as follows; complete anosmia (57.8%), troposmia (8.4%), hyposmia (2.9%), partial anosmia (2.6%) and euosmia (0.6%). Significantly increased prevalence of diabetes, hypertension asthma in the group with olfactory dysfunction (p < 0.001), chronic liver disease (p = 0.005), and hypothyroidism (p = 0.03). Conclusion: The development of ODs after Covid-19 infection was associated with mild disease form and lower hospitalization. In addition, it showed significant relationship with preexisting systemic diseases. Anosmia is the common modality of ODs.

Evaluation of Heart Rate Variability Parameters During Awake and Sleep in Refractory and Controlled Epileptic Patients.

Background: Alterations of heart rate variability (HRV) in epileptic patients were the field of interest of several studies for many reasons, particularly the contribution toward sudden unexpected death in epilepsy (SUDEP). Aim: We aimed at evaluation of autonomic dysfunction in epileptic patients during awake and sleep in addition to studying the association between SUDEP risk with different Holter parameters. Patients and Methods: The study included eighty epileptic patients (40 controlled epileptic patients and 40 refractory epileptic patients) compared to 30 volunteers as control group. They underwent detailed epileptic history, Chalfont seizure severity scale, sudden unexpected death in epilepsy (SUDEP)-7 risk score and 24 hour Holter monitoring to assess HRV parameters. Results: Patients with refractory epilepsy had longer duration of epilepsy with increased number of used AEDs compared to controlled epileptic group. Both controlled and refractory epileptic patients had significantly higher average heart rate (AV.HR), sympatho-vagal ratio (low-frequency/high-frequency (LF/HF) ratio in 24 hours, daytime, and nighttime), and LF and HF values compared to controls. The rMSSD (the root mean square of difference between successive normal intervals), Tri.Index (triangular index), and pNN50 (percentage of the number of pairs of consecutive beat-to-beat intervals that varied by 50 ms) were significantly reduced in both epileptic groups compared to controls. Among refractory epileptic patients, patients with generalized epilepsy had significantly higher severity epileptic scale, average heart rate, minimum heart rate, and LF/HF night, in addition to lower rMSSD and pNN50 compared to patients with focal epilepsy. We found positive correlation between the following Holter indices (LF/HF 24, LF/HF day, and LF/HF night) and the duration of the epilepsy, while negative correlations between Tri.Index, LF, and HF and the epileptic duration were detected. SUDEP-7 risk was negatively correlated with pNN50 and rMSSD; meanwhile, it was positively correlated with LF/HF 24. The severity of epilepsy among refractory epileptic patients was positively correlated with average heart rate but negatively correlated with pNN50 and rMSSD. Using linear regression analysis, we found that pNN50 and rMSSD could predict SUDEP-7 risk and severity of epilepsy in refractory epileptic patients. Conclusion: Epileptic patients (particularly refractory patients with generalized EEG findings and long duration) had reduced heart rate variability and hence impairment of parasympathetic activity with increased susceptibility for adverse outcomes. Moreover, pNN50 and rMSSD could be used as predictors for SUDEP-7 risk as well as severity of epilepsy in refractory epileptic patients.

Evaluation of QT dispersion in epileptic patients and its association with SUDEP risk.

BACKGROUND: Mortality in epileptic patients was attributed to sudden unexpected death in epilepsy (SUDEP). The precise pathophysiology of SUDEP is not fully understood, yet prolongation of ventricular repolarization particularly QTc interval suggested to be one of the contributing risk factor for SUDEP. OBJECTIVES: We aimed at evaluation of QTc and QT dispersion (QTD) in patients with epilepsy (both refractory and well-controlled epilepsy) and their association with the epileptic severity and sudden unexplained death (SUDEP) risk. PATIENTS AND METHODS: The study included eighty epileptic patients (40 controlled epileptic patients and 40 refractory epileptic patients) compared to thirty non-epileptic volunteers as the control group (patients with history of cardiovascular comorbidities or exposure to antiarrhythmic drugs were excluded from the study). All participants were subjected to clinical evaluation including detailed epileptic history with assessment of SUDEP 7 risk, severity scale, 12 leads surface ECG to measure QTc & QTD, 24 h Holter monitoring to assess heart rate variability (HRV) parameters. RESULTS: Controlled and refractory epileptic patients demonstrated increased average QTc and QTD values compared to control group (450.1 ± 18.9 vs. 412.3 ± 12.3 ms, p < 0.0001, 452.1 ± 19.0 vs. 412.3 ± 12.3 ms, p < 0.0001 respectively) (45.6 ± 14.9 vs. 15.4 ± 6.8 ms, p < 0.001, 70.6 ± 18.1 vs. 15.4 ± 6.8 ms, p < 0.0001 respectively). Refractory epileptic patients had a significantly higher incidence of abnormal QTD > 50 ms compared to controlled epileptic patients (32.5% vs. 90%, p < 0.005). Refractory epileptic patients with generalized form had significantly higher severity scale in addition to significantly impaired rMSSD and pNN50 compared to those with focal form (1072.7 ± 722.7 vs. 429.1 ± 180.4, p < 0.03, 17.11 ± 4.6 vs. 26.4 ± 7.9 ms, p < 0.004 and 2.9 ± 1.8 vs. 7.8 ± 4.1%, p < 0.003 respectively). Among refractory epileptic patients, the duration of epilepsy, rMSSD and QTD significantly correlated with SUDEP-7 risk (r2 =0.199, p < 0.005, r2 =0.623, p < 0.0001 and r2=0.44, p < 0.0001 respectively). CONCLUSIONS: The current study stands out the importance of evaluating QTc and QTD in 12-lead ECG recordings in epileptic patients and signifying their association with SUDEP-7 risk among refractory epileptic patients.

Utility of Lung Ultrasound in Decision-making to Prioritize Hospital Admission for COVID-19 Patients: A Developing Country Perspective.

BACKGROUND AND AIMS: In the midst of this pandemic, planning the prioritization of hospital admissions for patients affected with COVID-19 should be of prime concern, particularly in healthcare settings with limited resources. Thus, in this study, we aimed to develop a novel approach to triage COVID-19 patients and attempt to prioritize their hospital admission using Lung Ultrasonography (LUS). The efficacy of LUS in triaging suspected COVID-19 patients and assessing the severity of COVID-19 pneumonia was evaluated; the findings were then compared with those obtained by chest computed tomography (CT). METHODS: This multicenter, cross-sectional study comprised 243 COVID-19 patients who presented to the emergency department in 3 major university hospitals in Egypt. LUS was performed by an experienced emergency or chest physician, according to the local protocol of each hospital. Demographic, clinical, and laboratory data were then collected from each patient. Each patient was subjected to chest CT scans and LUS. RESULTS: The mean age of the 243 patients was 46.7 ± 10.4 years. Ground-glass opacity, subpleural consolidation, translobar consolidation, and crazy paving were reported in the chest CT scans of 54.3%, 15.2%, 11.1%, and 8.6% of the patients, respectively. B-line artifacts were observed in 81.1% of the patients (confluent pattern, 18.9%). The LUS findings completely coincided with the CT findings (Kappa agreement value, 0.77) in 197 patients (81.1%) and offered a diagnostic sensitivity of 74%, diagnostic specificity of 97.9%, positive predictive value of 90.2%, and negative predictive value of 93.6% for the COVID-19 patients. Following the addition of O2 saturation to the lung imaging findings, the ultrasound method was able to demonstrate 100% sensitivity and specificity in accurately differentiating between severe and non-severe lung diseases. CONCLUSION: LUS with oxygen saturation might prove to be effective in prioritizing the hospital admission of COVID-19 patients, particularly in healthcare settings with limited resources.

T-Natural Killers and Interferon Gamma/Interleukin 4 in Augmentation of Infection in Foot Ulcer in Type 2 Diabetes.

BACKGROUND: The link between immune system and type 2 diabetes mellitus (T2DM) pathogenesis attracted attention to demonstrate the role of immune cells and their secreted cytokines in T2DM development and its subsequent foot complications. OBJECTIVE: To investigate the relation between T Natural killer cell (TNK) %, Interleukin 4 (IL4) and Interferon gamma (IFN-γ) and diabetic foot infection (DFI) development in patients with diabetic foot ulcer (DFU). PATIENTS AND METHODS: Ninety patients with diabetes were included in this work, divided as T2DM group (n=30), DFU group (n=30), and DFI group (n=30). TNK% was detected using flow cytometry. Serum IL4 and IFN-γ were measured by ELISA. Diabetes biochemical parameters were also analyzed. RESULTS: Significant decrease was detected in TNK% and IFN-γ in DFI group compared to other 2 groups (P<0.001). Significant decrease was detected in serum levels of IL4 in DFI group compared to T2DM group (P=0.006). IFN-γ/IL4 was significantly decreased in DFI compared to DFU group (P=0.020). There was a significant correlation of TNK% with both IL4 and IFN-γ (r=0.385, P<0.001; r=0.534, P<0.001, respectively). Significant negative correlation of TNK% with HbA1c and LDL was revealed (r=-0.631, P<0.001; and r=-0.261, P=0.013, respectively), while a positive correlation was seen with HDL (r=0.287, P=0.006). A significant negative correlation of IL4 with HbA1c  was found (r=-0.514, P<0.001;. As for IFN-γ, a significant negative correlation with HbA1c and LDL was detected (r=-0.369, P< 0.001; r=-0.229, P=0.030). TNK % and IFN-γ level showed negative correlations with disease duration/year (r=-0.546, P< 0.001; r=-0.338, P=0.001,respectively). CONCLUSION: Decline in TNK frequency has essential role in T2DM pathogenesis and subsequent foot complications. Downregulation of TNK% and IFN-γ level have potential roles in predicting infection of diabetic ulcer and are correlated with disease duration.