Association of simple hematological parameters with disease manifestations,activity, and severity in patients with systemic sclerosis

Clinical Rheumatology - Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), mean platelet volume (MPV), and red cell distribution width (RDW) may potentially reflect...     

Patients with Primary Immunodeficiencies in Pediatric Intensive Care Unit: Outcomes and Mortality-Related Risk Factors

Purposes

The aims of this study were to review the frequency, characteristics, and the clinical course of primary immunodeficiency (PID) patients admitted to pediatric intensive care unit (PICU) and attempt to identify factors related with mortality that might predict a poor outcome.

Methods

We performed a retrospective review of children with PID aged 1 month to 18 years and admitted to PICU from January 2002 to January 2012 in our tertiary teaching children’s hospital.

Results

There were a total of 51 patients accounting for 71 admissions to the PICU. The most common diagnosis was severe combined immunodeficiency. Respiratory problems were the leading cause for admission. A total of 20 patients received hematopoietic stem cell transplantation. Immune reconstitution was achieved in 9 (45 %) patients and eight of them did survive. In all 56 % of all admission episodes resulted in survival. Risk factors for mortality included requirement of mechanical ventilation (P?<?.001), number of organ system failure (P?=?.013), need for renal replacement therapy (P?<?.001), use of inotropes (P?<?.001), higher Pediatric Logistic Organ Dysfunction (PELOD) score (P?=?.005), and length of PICU stay (P?<?.001).

Conclusions

This is the first study regarding the outcome and mortality-related risk factors for PID patients requiring PICU admission. We suggest that PICU management is as important as early diagnosis and treatment for these patients. Prediction of those at risk for poorer outcome might be beneficial for accurate intensive care management and survival.     

Assessment of Neuropsychological Late Effects in Survivors of Childhood Leukemia

The neurologic dysfunctions caused by treatment may affect health and quality of life in survivors of childhood leukemia. The objective of this study was to identify the neuropsychological late effects of leukemia treatment to provide an assessment about the degree and incidence of these late effects. Neurological and ophtalmological examination, cranial magnetic resonance imaging (MRI), auditory and neurocognitive tests, and questionnaires of quality of life were performed to 44 acute leukemia survivors at least 5 years after diagnosis. Median time since completion of chemotherapy was 7.5 years (2–18) and median age at the time of the study was 16.4 years (8–31). At least one or more late effects detected by physical examination (PE), neurological tests, or neurocognitive tests encountered in 80% of the patients, and 64% of the patients specified at least one complaint in the quality of life questionnaire. MRI revealed pathological findings in 18% and electroencephalogram (EEG) abnormalities were present in 9% of the patients. Evaluation of total intelligence scores revealed that 30% of patients’ IQ scores were <80 and 70% of the patients’ scores demonstrated neurocognitive dysfunctions. The patients >6 years at the time of diagnosis were found to have more psychological problems and higher rates of smoking and alcohol consumption. The most frequent complaint was headache and the most common problem in school was denoted as difficulty in concentration. Our study demonstrated that most of the survivors of childhood leukemia are at risk of developing neuropsycological late effects.     

Nasopharyngeal carriage of Streptococcus pneumoniae in healthy Turkish children after the addition of PCV7 to the national vaccine schedule

The aim of this study was to determine serotype distribution and investigate antimicrobial resistance patterns of Streptococcus pneumoniae in healthy Turkish children in the era of community-wide pneumococcal conjugate vaccine (PCV7). The study was conducted on 1,101 healthy children less than 18 years of age. Specimens were collected with nasopharyngeal swabs between April 2011 and June 2011. Penicillin and ceftriaxone susceptibilities were determined by E-test according to the 2008 Clinical Laboratory Standards Institute, and serotypes of the isolates were determined by Quellung reaction. The nasopharyngeal pneumococcal carriage rate was 21.9 % (241/1,101). Using the meningitis criteria of minimum inhibitory concentration values, 73 % of the isolates were resistant to penicillin and 47.7 % of them were resistant to ceftriaxone. Half of all pneumococcal isolates were serotyped as 19F (15.2 %), 6A (15.2 %), 23F (10.3 %), and 6B (9.3 %) and surprisingly, no serotype 19A was isolated. Serotype coverage rates of PCV7 and non-PCV7 were 46.2 and 53.8 %, respectively. The most common penicillin- and ceftriaxone-resistant serotypes were 6A, 6B, 14, 19F, and 23F. Penicillin- and ceftriaxone-resistant isolates were more prevalent in serotypes covered by PCV7 than the non-PCV7 serotypes. Conclusion: After the community-wide PCV7 vaccination, more non-PCV7 serotypes were isolated from the carriers compared to the time before PCV7 was used especially the serotype 6A, and the antimicrobial resistance of pneumococci was significantly increased.     

Evaluation of Systemic Levels of Neutrophilic Enzymes in Patients With Hypertension and Chronic Periodontitis

Background: Inflammation stimulates neutrophils to release their enzymes into the extracellular matrix. The aim of the present study is to investigate the serum levels of matrix metalloproteinase (MMP)‐8, MMP‐9, tissue inhibitor of MMP (TIMP)‐1, myeloperoxidase (MPO), and neutrophil elastase (NE) in patients with hypertension and chronic periodontitis (CP). Methods: A total of 95 patients were included in the study. Patients were categorized into three groups: healthy control (n = 29), hypertensive control (n = 32), and hypertensive CP (n = 34). Periodontal parameters were recorded, and serum samples were collected from each participant. Serum MMP‐8, MMP‐9, TIMP‐1, MPO, and NE levels in circulation were assessed by enzyme‐linked immunosorbent assay. Results: The hypertensive CP group had significantly higher serum MMP‐8, MMP‐9, and NE levels than the healthy control group (P <0.05). All study groups had similar serum TIMP‐1 levels (P >0.05). Significantly higher serum MPO levels were detected in patients with hypertension and CP than healthy controls and hypertensive controls (P <0.05); however, the difference in serum MPO levels was not significant between the healthy controls and hypertensive controls (P >0.05). There was no significant difference in MMP‐8/TIMP‐1 ratio among the study groups (P >0.05). MMP‐9/TIMP‐1 ratio was significantly higher in patients with hypertension and CP than healthy controls (P <0.05). Conclusions: The presence of hypertension along with CP has a considerable effect on serum neutrophilic enzyme levels, except TIMP‐1. However, the levels of these enzymes do not seem to be affected by the presence of hypertension only. Further studies including patients who have only CP might help illuminate the effect of CP on these enzymes in patients with hypertension.     

Alpha 2 integrin gene (ITGA2) polymorphism in renal transplant recipients with and without drug induced gingival overgrowth

Background

Variances in fibroblasts’ α2β1 integrin intensity may lead to altered adhesion to type I collagen and consequently to suppression of phagocytosis which may be one of the mechanisms for drug induced gingival overgrowth. The present study aimed to evaluate the genotype and allele frequencies of α2 integrin +807 gene in renal transplant patients with and without gingival overgrowth.

Material and methods

Seventy renal transplant patients with cyclosporine A (CsA)-induced gingival overgrowth (CsA GO+) were enrolled. Renal transplant patients without GO medicated with CsA (CsA GO−; n = 79) and tacrolimus (Tac; n = 52) served as controls. DNA was obtained from peripheral blood and ITGA2 +807C/T polymorphism was genotyped by polymerase chain reaction and restriction fragment length polymorphism method. Clinical parameters including probing depth and plaque, papilla bleeding and hyperplasia indexes were recorded. Chi-square, Kruskal–Wallis and Mann–Whitney tests were used in statistical analysis.

Results

Clinical parameters of CsA GO+ group were significantly higher than those of the CsA GO− and Tac groups (p < 0.05). ITGA2 807C/T genotype and allele frequencies of study groups were similar (p > 0.05).

Conclusion

Within the limits of the present study it can be concluded that ITGA2 +807 gene polymorphism is not associated with susceptibility to CsA-induced GO.     

The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T/hACE2+TMPRSS2, and virus neutralization assay using xCELLigence MP real-time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of montelukast both on the main protease enzyme inhibition and virus entry into the host cell (spike/ACE2). The virus neutralization assay results showed that SARS-CoV-2 virus activity was delayed with montelukast for 20 h on the infected cells. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and, if its effect is proved in clinical phase studies, it should be used against coronavirus disease 2019 (COVID-19).