Evaluating circulating cell-free DNA and DNA integrity index as biomarkers in non-small cell lung cancer.

BACKGROUND: Analysis of free DNA molecules shed from tumour cells in plasma of patients referred as circulating tumour DNA (ctDNA) with reference to physiological circulating cell-free DNA (cfDNA) is nowadays exploited as liquid biopsy and is considered a new emerging promising biomarker for diagnosis, selection of proper treatment, and prognosis of cancer. DNA integrity index (DII) is assessed by calculating the ratio between the concentration of long cfDNA strands released from tumour cells (ALU247) and the short strands released from normal cells (ALU115). The aim of the current study was to evaluate DII as a potential diagnostic and prognostic biomarker of NSCLC. METHODS: Our study included 48 NSCLC patients diagnosed as primary NSCLC before starting treatment, 30 COPD patients diagnosed clinically, radiologically, and subjected to chest high-resolution computerized tomography, and 40 healthy controls. cfDNA concentration and DII were measured by quantitative real-time polymerase chain reaction (qPCR). RESULTS: ALU115, ALU247, and DII were significantly higher in NSCLC compared to COPD patients (p < 0.0001) and controls (p < 0.0001) and in COPD patients compared to control subjects (p < 0.0001). DII positively correlated with the stage of tumour (p = 0.01), tumour metastasis (p = 0.004), and with adenocarcinoma compared to other histopathological types (p = 0.02). To evaluate clinical utility of DII in NSCLC, ROC curve analysis demonstrated an AUC of 0.91 at a cut-off value of 0.44 with total accuracy = 85.6%, sensitivity = 90%, specificity = 83%, PPV = 78.1%, and NPV = 92.1%. CONCLUSION: cfDNA and DII represent a promising diagnostic and prognostic tool in NSCLC. This type of noninvasive liquid biopsy revealed its chance in the screening, early diagnosis, and monitoring of NSCLC.

Burden and Outcome of Vitamin D Deficiency Among Critically Ill Patients: A Prospective Study.

BACKGROUND: Vitamin D deficiency is a prevalent condition among critically ill patients. Information about the relationship between vitamin D levels and outcomes in the intensive care unit (ICU) is sparse. PURPOSE: To evaluate vitamin D status among critically ill patients and its relevance to severity of illness, ICU stay period, and mortality. METHODS: This prospective multicenter study was conducted in the ICUs of Fayoum, Cairo, Alazhar, and Ain Shams university hospitals. All patients were subjected to interview questionnaire, laboratory investigation, vitamin D level assessment, and severity of illness evaluation using the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score. RESULTS: In total, 250 patients were included in the study. The median age was 62 (40-73) years, and most patients were male (52%). The median serum level of vitamin D was 19 (7-40.6). Vitamin D was deficient in 197 patients (78.8%) on admission. While we grouped the ICU patients as vitamin D deficient, insufficient, and sufficient, vitamin D-deficient patients had more severe diseases (mean APACHE II score, 44 ± 15; P = .014). Prolonged ICU stay was observed among the deficient group but with no significant association. The overall mortality rate was 6.8%; of these, 70.5% were vitamin D-deficient patients. However, logistic regression analysis demonstrated that vitamin D deficiency was not an independent risk factor for mortality. CONCLUSION: Vitamin D insufficiency is common in critically ill patients (69%); it is associated with more severity of illness, but it is not an independent risk factor for longer ICU stay or mortality.

CLINICAL SIGNIFICANCE OF SERUM N-TERMINAL PRO C-TYPE NATRIURETIC PEPTIDE IN HEPATITIS C-RELATED CHRONIC LIVER DISEASES.

To evaluate the clinical utility of serum levels of N-terminal pro C-type natruretic pep-tide (NT-pro CNP) in patients with hepatitis C related chronic liver disease (CLD), in prospective to disease complications and progression. This study included 66 hepatitis C-related CLD patients with and without ascites and 15 healthy individuals (control group). Serum NT-pro CNP was measured by ELISA. A stepwise progressive increase in NT-pro CNP levels was recorded through controls, patients without ascites and patients with ascites (p< 0.05). In addition, patients with hematemesis or encephalopathy had more than its double values than those without (p<0.01). Moreover, a significant difference was observed in the marker levels among esophageal varcies stages 1, 2, 3 (H=13.679, p=0.001), with highest levels in grade 3. NT-pro CNP correlated positively with alpha fetoprotein (rs =0.455, p=0.008) with no significant correlation neither with MELD nor Child scores (p>0.05). ROC curve analysis revealed the overall performance of the marker in discriminating CLD patients collectively from controls, the optimum cut-off level was 85 ng/L (AUC= 0. 803, sensitivity 84.8%& specificity 53.3%). An increased level of NT-pro CNP is a promising non-invasive marker of hepatitis C related CLD complications and disease progression.

Evidence of association of interleukin-23 receptor gene polymorphisms with Egyptian rheumatoid arthritis patients.

BACKGROUND: The identification of additional genetic risk factor is an on-going process that will aid in the understanding of rheumatoid arthritis (RA) aetiology. A genome-wide association scan in Crohn's (CD) disease highlighted the interleukin-23 receptor (IL23R) gene as a susceptibility factor. Since the IL-23/IL-17 pathway is known to associate with other autoimmune disease, including rheumatoid arthritis and systemic sclerosis, we hypothesised that IL23R could be a shared susceptibility gene. The rare allele of IL23R single nucleotide polymorphism (SNP) rs11209026 (Arg381Gln) confers strong protection against CD. Our aim was to analyse IL23R SNP (rs11209026, rs2201841, and rs10889677) and to detect its association with RA in Egyptian patients. METHODS: A group of Egyptian patients with RA (n=120) and apparently healthy persons as controls (n=120) was genotyped for rs11209026, rs2201841 and rs10889677 by real time/polymerase chain reaction (real-time/PCR) for the first SNP and restriction fragment length polymorphism/PCR (RFLP/PCR) in the last two SNPs. RESULTS: Our data emphasise that the AA genotype of rs11209026 (Arg381Gln) was significantly associated with RA patients compared to the controls (P value=0.001).We did not find any significant association between either rs2201841 or rs10889677 and the development of rheumatoid arthritis (P value=1.000 & 0.562 respectively). CONCLUSION: Our results suggest that IL23 receptor AA genotype variant of rs11209026 would contribute to RA aetiology; consequently, it might be a genetic marker for RA. We need to address the subgroup of patients who will benefit from the selective suppression of the IL23 signalling which would represent new perspectives toward a personalized therapy of RA patients by further studies.

Effect of vitamin D therapy on interleukin-6, visfatin, and hyaluronic acid levels in chronic hepatitis C Egyptian patients.

OBJECTIVES: We aimed to compare serum levels of interleukin-6, visfatin, and hyaluronic acid in chronic hepatitis C Egyptian patients who received standard of care (SOC) therapy for chronic hepatitis C virus (HCV) consisting of pegylated interferon (PEG-IFN) and ribavirin (RBV) and in those who received SOC with vitamin D (vit D) for 48 weeks in HCV genotype 4a subjects. DESIGN AND METHODS: One hundred chronic HCV patients were classified into two groups: study 50 patients received SOC therapy PEG-IFN/RBV + vit D and control 50 patients received SOC PEG-IFN/RBV without vit D. Both groups were followed up at 12 weeks, 24 weeks, and 48 weeks of treatment. RESULTS: Results showed a significant elevation in vit D levels in the group treated with SOC and vit D compared to SOC group and a reduction in HCV RNA from the 12th week to reach zero level in the 24th week. Interleukin-6, visfatin, and hyaluronic acid levels were also reduced significantly. Alanine transaminase and aspartate transaminase biomarkers were significantly reduced, indicating decreased liver injury. CONCLUSION: SOC PEG-IFN/RBV + vit D therapy for chronic HCV led to reduced interleukin-6, visfatin, and hyaluronic acid levels and follow up liver biochemical biomarkers as aspartate transaminase and alanine transaminase indicates proper liver healing and monitoring.

The role of procalcitonin as a guide for the diagnosis, prognosis, and decision of antibiotic therapy for lower respiratory tract infections.

OBJECTIVES: To assess the value of PCT as a rapid and sensitive marker for diagnosis, prognosis, and therapy of lower respiratory tract bacterial infections necessitating antimicrobial treatment and comparing this marker with other markers of infections including C-reactive protein (CRP) and total white-blood cell counts (WBCs). PATIENTS AND METHODS: Sixty Patients were enrolled in the study, they were subjected to complete history taking, physical examination, laboratory investigations including complete blood count, blood gases, blood chemistry, bacteriological culture for sputum and blood, serology for atypicals, and PCR for respiratory viruses, serum C-reactive protein (CRP) and PCT levels were measured. The patients were divided into two groups, group 1 included 26 patients who were culture negative for bacterial infection and group 2 included 34 patients who were culture positive. Group 2 patients were given antibiotic therapy according to the culture sensitivity. RESULT: The results revealed that, there was no significant difference between group 1 and group 2 patients as regards age, sex, clinical manifestations, final diagnosis, white blood cell counts, blood gases, number of admitted patients, intensive care unit admission and length of hospital stay. A significant increase of PCT and CRP levels was detected in group 2 compared to group 1 at initial diagnosis. At cutoff value >0.5 ng/ml, PCT gave a sensitivity of 94.1%, specificity of 88.4%, positive predictive value (PPV) of 91.4%, negative predictive value (NPV) of 92% and diagnostic efficiency of 91.6% for diagnosis of respiratory tract bacterial infections. However, at a cutoff value >8 mg/L, CRP gave a sensitivity of 85.2%, specificity of 76.9%, PPV of 82.8%, NPV of 80% and diagnostic efficiency of 81.7%. After antibiotic therapy PCT and CRP levels dropped in group 2 patients as compared to their pre-treatment levels. CONCLUSION: Serum PCT level could be used as a novel marker of lower respiratory tract bacterial infections for diagnosis, prognosis and follow up of therapy. This reduces side-effects of an unnecessary antibiotic use, lowers costs, and in the long-term, leads to diminishing drug resistance.

Laryngeal involvement in juvenile idiopathic arthritis patients.

Juvenile idiopathic arthritis (JIA) is an autoimmune diseases characterized by chronic arthritis and systemic manifestations. Autoimmune diseases can affect the upper airways including the larynx. The aim of this study was to investigate laryngeal involvement in JIA patients and its possible association with JIA disease parameters. Fifty consecutive JIA patients were screened for laryngeal abnormalities using flexible fiberoptic laryngoscope and laryngeal computerized tomography. Laryngeal abnormalities were detected in nine (18%) of our cases, with cricoarytenoiditis in six cases (12%) and a rheumatoid nodule in the pyriform fossa in only one case (2%). Diffuse congestion and edema of the posterior part of the larynx with normal vocal cord mobility was detected in two cases (4%). In our study, laryngeal abnormalities were significantly higher in patients with polyarticular seropositive disease subtype and also were significantly higher in patients with longer disease duration, higher disease activity scores, and those with erosive disease. JIA may affect the larynx. Laryngeal involvement in JIA patients is more in polyarticular seropositive cases. JIA patients have to be subjected to thorough otolaryngologic examination for early diagnosis and prompt management.