The effect of danger-associated molecular patterns on survival in acute graft versus host disease.

Danger-associated molecular patterns (DAMPs) are molecules that can initiate and maintain robust inflammatory responses and were investigated in the pathogenesis of graft versus host disease (GvHD). Uric acid (UA) and fibrinogen (Fib) are DAMPs released from damaged tissue during allogeneic hematopoietic stem cell transplantation (allo-HCT) and GvHD. We aimed to evaluate the effects of UA and Fib levels on survival in GvHD. One hundred seventy-four patients with grade 2-4 acute GvHD were included. UA and Fib levels were evaluated on allo-HCT day 0 and GvHD on days 0, 7, 14, and 28. Fib GvHD day 0 was the independent predictor for overall survival (OS), non-relapse mortality (NRM), and progression-free survival in multivariable models (HR 0.98, p < 0.001; HR 0.98, p = 0.001, HR 0.98, p = 0.006, respectively). Also UA GvHD day 28 was the independent predictor for OS and NRM (HR 0.77, p = 0.004; HR 0.76, p = 0.011, respectively). Our results indicated that hypouricemia and hypofibrinogenemia were associated with a significantly shorter OS and higher NRM. UA and Fib are remarkable molecules in GvHD because they are routinely utilized, readily available, can be therapeutic targets, and have DAMPs and antioxidant features.

The investigation of adrenal involvement in carbapenem resistant Acinetobacter baumannii sepsis: experimental mouse model

Background/aim: In the last years, incidence of carbapenem resistant Acinetobacter baumannii sepsis is increasing with high mortality. However, it is not clear whether this is due to inadequate antimicrobial choice or a more severe clinical course. We aimed to evaluate the inflammation and adrenal involvement in the carbapenem resistant A. baumannii by using experimental mouse model sepsis. Materials and methods: Balb/c female mice were randomly put into control and three sepsis groups ( A. baumannii susceptible to carbapenem-CSAB-, A. baumannii resistant to carbapenem-CRAB-, Escherichia coli). A total of sixty mice were included in this study with each group having 15 mice. Mice were sacrificed 72 h after bacterial inoculation, and blood was taken from each mouse for the assessment of cytokines and corticosterone. Both adrenal glands were dissected; one was used for culture and the other was used for histopathological examination. Bacterial loads of organs were calculated as CFU/g. The histopathological changes, bacterial levels in adrenal and cytokine and corticosterone levels were assessed and compared among the groups. Results: The bacterial level was higher in E. coli (108, 45 ±30, 55 log10 CFU/g) (mean±SD) than other sepsis groups. The lowest level of corticosterone was observed in the E. coli group (p < 0.001). TNF alpha level was highest in the CRAB and E. coli group and this difference was statistically significant than control group (p < 0.05). The IL-6 level in CRAB was significantly higher than the control group (10, 20 pg/mL). The adrenal gland congestion was significantly severe in all the sepsis groups compared to the control. In the group comparison, congestion was significantly more severe in the E. coli group than in CSAB and CRAB groups. Conclusion: Adrenal involvement and inflammatory reactions are seen in E. coli sepsis and in CRAB sepsis. These findings will be focused on in future clinical trials.

The efficacy of mesenchymal stem cell therapy in experimental sepsis induced by carbapenem-resistant K. pneumoniae in neutropenic mice model.

Especially in recent years, the intensive use of antibiotics has caused multiple drug resistance in Klebsiella pneumoniae. In the absence of a new antibiotic, alternative treatment options have emerged. The aim of this study was to investigate the efficacy of mesenchymal stem cell (MSC) treatment of carbapenem-resistant K. pneumoniae sepsis in neutropenic murine model. BALB-c mice were divided into two groups as control (positive and negative) and treatment groups (colistin, colistin + MSC, MSC) after the development of neutropenia with cyclophosphamide. Sepsis was developed in mice by intraperitoneal injection of carbapenem-resistant K. pneumoniae. Three hours after inoculation of the bacteria, colistin and MSC were given in the treatment groups intraperitoneally. Colistin injection was repeated every 12 h, while MSC was administered as 2nd dose after 48 h. Mice were sacrificed at 48 and 96 h. The right lung and half of the liver were quantitatively cultured, and the bacterial load was calculated as cfu/g. The left lung, the other half of the liver tissue, and both kidneys were evaluated histopathologically. IL-6 and TNF-α cytokine levels in mouse sera were determined by ELISA. Bacterial loads in lung and liver tissues of neutropenic mice were lower in the MSC + colistin-treated group at 48 and 96 h compared to colistin and MSC monotherapy groups. Also, bacterial eradication was started the earliest in MSC + colistin group. It was concluded that combining colistin with MSC provided improved therapeutic effects compared to colistin or MSC monotherapy.

Pleuropulmonary blastoma: A report of two cases.

Pleuropulmonary blastoma is a rare and aggressive childhood tumor of mesenchymal origin. It has a poor prognosis and mainly classified as cystic (type 1), mixed type (type 2), and solid (type 3). Herein, we present two cases of pleuropulmonary blastoma type 3 presenting with pneumothorax, a rare clinical presentation of pleuropulmonary blastoma, which was successfully treated with surgery.

Increased EGFR mRNA Expression Levels in Non-Small Cell Lung Cancer.

OBJECTIVE: In this study, we investigated the frequency of Epidermal growth factor receptor (EGFR) gene mutations, the level of EGFR mRNA and protein expressions in Turkish population for indicating substantial differences in the frequency of EGFR mutations, EGFR amplification and EGFR protein expression between populations and the effect of these parameters in response to EGFR tyrosine kinase inhibitors. MATERIALS AND METHODS: The study included 34 patients with non-small cell lung cancers. The RNA and DNA were extracted from the normal and tumor side of the lung tissue removed by surgery. To investigate the most common mutations in the EGFR gene, exon 19 was sequenced and mutation specific PCR was performed for detecting the L858R mutation in exon 21. EGFR mRNA expression was measured by relative quantitative reverse transcription PCR. The EGFR protein levels were detected with immunohistochemistry methods from the sections of the patients' paraffin blocks. RESULTS: No EGFR mutation in exon 19 or L858R mutation in exon 21 were detected in the patients. Overexpression of EGFR gene mRNA was identified in 16 of 34 (%47) patients and overexpression of EGFR protein was detected in 15 of 34 (%44) patients. Statistical analysis was not significant for the correlation between sex, age, smoking, histopathology, pathological stage and overexpression of EGFR mRNA and protein. CONCLUSION: It was found that in Turkish population, EGFR mutation in exon 19 and L858R mutation were very rare, EGFR protein expression was similar and EGFR mRNA expression significantly increased compared to the literature. Markedly increased EGFR mRNA expression ratios in the absence of activating mutations showed that identifying the EGFR mRNA expression level for prediction of response to EGFR tyrosine kinase inhibitors might be significant in the Turkish population.

Clinical significance of progastrin-releasing peptide, neuron-specific enolase, chromogranin a, and squamous cell cancer antigen in pulmonary neuroendocrine tumors

Background/aim: It is not always easy to diagnose pulmonary neuroendocrine tumors (PNETs). The aim of the present study is to make a differential diagnosis by studying the same markers in patients with non-small-cell lung carcinoma (NSCLC), patients with benign lung disease (chronic obstructive pulmonary disease and pneumonia), and healthy volunteers to determine the roles of these markers in pulmonary neuroendocrine tumor diagnosis and to identify their power. Materials and methods: A total of 100 participants including 23 PNET patients and 28 NSCLC patients who were pathologically di-agnosed but not yet treated, 25 participants with benign disease, and 24 healthy volunteers were included in this cross-sectional study. Results: No significant difference was found between the chromogranin A (CgA) and squamous cell carcinoma antigen 1 (SCCA1) values among the groups (PNET, NSCLC, benign, healthy volunteers), but the difference in progesterone-releasing peptide (ProGRP), neuron-specific enolase (NSE), and adjusted NSE was statistically significant (P values were respectively ProGRP, P = 0.006; NSE, P = 0.015; NSE adjusted, P = 0.09). In a comparison of the PNET and NSCLC groups, having a ProGRP value higher than 84.6 pg/mL re-vealed PNET with 60.9% sensitivity and 89.3% specificity (P = 0.001). Conclusion: The ProGRP value is the only indicator that distinguishes the PNET group from the other 3 groups.

Brown tumor of the thoracic spine presenting with paraplegia in a patient with peritoneal dialysis.

Secondary and tertiary hyperparathyroidism is an important problem of chronic kidney disease. Brown tumor is a benign, unusual, reactive lesion as a result of disturbed bone remodeling, from long-standing increase in parathyroid hormone level. Brown tumors may cause morbidity due to pressure symptoms on neural structures and spontaneous bone fractures. Herein, we presented a peritoneal dialysis patient with tertiary hyperparathyroidism under calcand calcitriol treatment for 4 years due to refusing of the parathyroidectomy operation. She admitted to hospital for sudden onset back pain with difficulty in gait and walking, and imaging studies showed an expansile mass lesion in the thoracic spine. She was operated for mass and diagnosed with brown tumor. After operation, she lost the ability of walking than become paraplegic and she underwent rehabilitation program. Preventive measures including calcitriol and cinacalcet may cause a modest decrease in parathyroid hormone levels but it should be remembered for the development of bone complications such as brown tumor formation in patients with moderate elevated PTH levels, especially those with tertiary hyperparathyroidism. Parathyroidectomy should be performed without delay in these cases.

The role of nonsteroidal anti-inflammatory drugs intramuscular injection in the development and severity of deep soft tissue infection in mice.

The aim of this study was to determine the role of nonsteroidal anti-inflammatory drugs (NSAID) injection on the severity of local infection and the effect on the progression of soft tissue infection (STI).The mouse model of STI with Group A streptococcus (GAS) was developed and treated with diclofenac sodium (DS) intramuscularly. Mice were divided into five groups: administered DS for 48 h before GAS (Group 1), GAS-DS and maintained DS for 48 h (Group 2), DS for 48 h (Group 3), GAS on zero time (Group 4), and control (Group 5). In vitro, a high concentration (40 mg/L) of DS inhibited GAS growth, whereas a lower concentration (0.4 mg/L) was not effective. Sepsis was observed in animals with DS and GAS inoculation (group 1 and 2). Group 4 had statistically significant higher bacterial load than groups 1 and 2. All groups had a higher inflammation rate than the control group. The median of TNF-alpha and mean IL-6 in the groups 1, 2, and 4 was significantly higher than those in the control group. Even if the animals that were treated with DS injection prior to the GAS inoculation had similar inflammation score, similar cytokine levels and low bacterial load in the tissue, they had a rather high rate of sepsis. In conclusion, DS injection prior to bacterial inoculation might predispose to bacteremia and sepsis.

Apparent diffusion coefficient in differentiation of pediatric posterior fossa tumors.

PURPOSE: To investigate the contribution of preoperative apparent diffusion coefficient (ADC) values in the differential diagnosis of pediatric posterior fossa tumors. METHODS: Forty-two pediatric patients (mean age 7.76 ± 4.58 years) with intra-axial tumors in the infra-tentorial region underwent magnetic resonance imaging. ADC measurement was performed using regions of interest, obtained from the solid component of the mass lesions. ADC ratios were calculated by dividing the ADC values from the mass lesions by the ADC values from normal cerebellar parenchyma. Lesions were categorized as juvenile pilocytic astrocytoma (JPA), ependymoma and medulloblastoma based on histopathological diagnosis. ADC values of the lesions and histopathological diagnoses were statistically correlated. RESULTS: Histopathological diagnosis showed that 14 lesions were JPA, 10 were ependymoma; 18 were medulloblastoma. Both ADC values and ADC ratios were significantly correlated with tumor types (p <0.05). Astrocytoma was distinguished from ependymoma with sensitivity 85.7% and specificity 90% using an ADC ratio ≥1.7 and medulloblastoma was distinguished from ependymoma with sensitivity 100% and specificity 88.89% using an ADC ratio ≤1.18. CONCLUSION: Preoperative ADC values could differentiate the main histological subtypes of pediatric posterior fossa tumors with high sensitivity and specificity.

Steel Wool-Aided Dermabrasion of Deep Partial-Thickness Burns.

Early tangential excision of the burn wound is essential for removal of necrotic tissue and promotion of burn wound healing process. However, the depth of the burn wound is not easily assessed during the tangential excision performed by hand-held dermatomes, and it may be possible to excise unburned vital dermis unnecessarily, which aids in primary epithelization of the burn wound by adnexal structures. We herein present early clinical results of steel wool-aided dermabrasion in patients with deep partial-thickness burns. This is a retrospective case study of 23 consecutive hospitalized patients with deep partial-thickness burns. All of the steel wool-aided dermabrasions were performed under general anesthesia within 48 hours after injury. Patients were excluded from the study if the admission was not within 24 hours after injury, and if the burn wound was entirely superficial partial- or full-thickness. Thirteen male and 10 female patients with a mean age of 26.2 ± 17.1 years were enrolled in the study. During the follow-up period, all of the patients had burn wounds primary epithelized on postburn day 15.1 ± 1.8, without any complications. None of the patients exhibited a mortal course, and redebridement or skin grafting of the previously dermabraded deep partial-thickness burn wounds were not required in any of the patients. Steel wool-aided dermabrasion is an easy, cost-effective, and reliable technique for the treatment of deep partial-thickness burns, which provides complete removal of necrotic tissue, preserves the vital dermis, reduces the requirement for skin grafting, and decreases length of hospital stay.

Prognostic value of SPARC expression in unresectable NSCLC treated with concurrent chemoradiotherapy.

BACKGROUND: The aim of the present study was to determine the predictive/prognostic value of the secreted protein, acidic and rich in cysteine (SPARC) in cases of unresectable, locally advanced, non-small cell lung cancer. MATERIALS AND METHODS: The study included 84 patients with Stage IIIA-B non-small cell lung cancer, undergoing simultaneous chemoradiotherapy including radiotherapy at a dose of 66 Gy and weekly docataxel (20 mg/m2) and cisplatin (20 mg/m2). SPARC expression was studied in biopsy material by immunohistochemical methods and correlations with treatment responses or survival were evaluated. RESULTS: Median overall survival was 16±2.73 (11.55-20.46) months for low expression vs 7±1.79 months (7.92-16.08) months for high expression (p=0.039), while median local control was 13±2.31 (8.48-17.5) months for low expression vs 6±0.85 (4.34-7.66) months for high expression (p=0.045) and median progression-free survival was 10±2.31 (5.48-14.5) months for low expression vs 6±1.10 (3.85-8.15) months for high expression (p=0.022). In both univariate and multivariate analyses, high SPARC expression was associated with significantly shorter overall survival (p=0.003, p=0.007, respectively), local control (p=0.008, p=0.036) and progression-free survival (p=0.004, p=0.029) when compared to low SPARC expression. No significant difference was detected between high and low SPARC expression groups regarding age, sex, T stage, N stage, histopathology and stage-related patient characteristics. CONCLUSIONS: High SPARC expression was identified as a poor prognostic factor in cases with locally advanced NSCLC treated with concurrent chemoradiotherapy.

The coincidence of familial mediterranean Fever and hypereosinophilia in a patient with hereditary elliptocytosis.

Familial Mediterranean fever (FMF) is a genetic disease with autosomal inheritance characterized by recurrent fever, abdominal pain, and serositis attacks. It is relatively common in the races and ethnical groups around Mediterranean Sea (Sephardic Jews, Armenians, Turks and Arabians). Hereditary elliptocytosis (HE) is common genetic defect of the red blood cell membrane skeleton. Spectrin mutations are the predominant causes of HE. Hypereosinophilia is defined as a number of eosinophil granulocytes equal or greater than 0.5 × 10(9)/L of circulating blood. The main causes are allergies and parasitic infections. This case report describes a Turkish female HE patient who presented with FMF and hypereosinophilia. Genetic analysis revealed heterozygous mutation in exon 10 of the MEFV gene (V726A). The patient was successfully treated with colchicine and steroid treatment at 3-month follow-up. To the best of our knowledge, this is the first report of association between FMF, HE, and hypereosinophilia.

A case of mucoepidermoid carcinoma of the bronchus presented with hydropneumothorax in a child.

Mucoepidermoid carcinoma is a rare pulmonary neoplasm seen in the pediatric population. We report a low grade mucoepidermoid carcinoma in a 12-year-old boy who presented with spontaneous pneumothorax.

Ectopic salivary gland of the base of the tongue: a rare cause of neonatal respiratory distress.

Neonatal upper airway obstruction is a life-threatening condition and requires rapid assessment and effective treatment. Malformations of the upper airway of a newborn can lead to acute respiratory distress. The aim of the present paper is to report the case of a newborn with respiratory distress due to a tongue base mass, which was removed surgically. The patient needed a tracheostomy tube for only three days and then could breathe spontaneously. However, he had swallowing problems, which decreased gradually over 9 months. Histopathologically, the mass was found to consist of mucous salivary glands, and was recorded as an ectopic salivary gland, which is extremely rare among the types of masses that may cause upper airway obstruction in a newborn.

Scabies mimicking mastocytosis in two infants.

Scabies is a common parasitic human infection in infants and children. However, diagnostic pitfalls are frequent in infants, in whom the clinical presentation is usually atypical and different from that in adults. In nodular scabies, lesions may be clinically or histologically misdiagnosed as Langerhans cell histiocytosis, insect bite reaction, non-Langerhans cell histiocytosis, lymphoma, or urticaria pigmentosa. We report two misleading cases of young infants (10- and 12-month-old infants) who presented with pruritic brown-red lesions on their trunks and showing a positive Darier's sign, suggestive of urticaria pigmentosa.

Atypical intracerebral schwannoma mimicking glial tumor: case report.

A rare case of a solitary schwannoma arising within parenchyma of the brain is reported. A 37-year old right-handed man presented with a 3- month history of progressive headaches, lethargy and vomiting. The initial diagnosis being considered was primary intracranial tumor, including high-grade astrocytoma, metastasis or lymphoma Histopathological examination revealed schwannoma. Cysts, calcification and mild to moderate peritumoral edema are common in intracerebral schwannomas. However, our case is atypical and has no cystic component, calcification or vascularization. The pathogenesis and neuroradiological findings of intraparenchymal schwannomas are discussed and we review the related literature.

A report of a desmoplastic non-infantile ganglioglioma in a 6-year-old boy with review of the literature.

Desmoplastic infantile gangliogliomas (DIG) are uncommon supratentorial brain tumors with a usually good prognosis despite an aggressive radiological appearance that typically occurs in infants below the age of 24 months. DIGs are exclusively supratentorial, generally have a voluminous size, and are partially cystic. Total surgical removal is sufficient for the treatment of these tumors, and no chemotherapy or radiotherapy is indicated if complete resection is achieved. Except for age difference, DIG and desmoplastic non-infantile gangliogliomas are radiologically and histologically similar. Non-infantile variants of this biologically benign intracranial neoplasm are rare; only 15 cases of non-infantile DIGs have been reported in the literature. As far as we know, this case is the 16th in literature. We reported the magnetic resonance imaging and histological findings of desmoplastic ganglioglioma in a 6-year-old boy.