Primary antibody deficiencies in Turkey: molecular and clinical aspects

Primary antibody deficiencies (PAD) are the most common subtype of primary immunodeficiencies, characterized by increased susceptibility to infections and autoimmunity, allergy, or malignancy predisposition. PAD syndromes comprise of immune system genes highlighted the key role of B cell activation, proliferation, migration, somatic hypermutation, or isotype switching have a wide spectrum from agammaglobulinemia to selective Ig deficiency. In this study, we describe the molecular and the clinical aspects of fifty-two PAD patients. The most common symptoms of our cohort were upper and lower respiratory infections, bronchiectasis, diarrhea, and recurrent fever. Almost all patients (98%) had at least one of the symptoms like autoimmunity, lymphoproliferation, allergy, or gastrointestinal disease. A custom-made next-generation sequencing (NGS) panel, which contains 24 genes, was designed to identify well-known disease-causing variants in our cohort. We identified eight variants (15.4%) among 52 PAD patients. The variants mapped to BTK (n?=?4), CD40L (n?=?1), ICOS (n?=?1), IGHM (n?=?1), and TCF3 (n?=?1) genes. Three novel variants were described in the BTK (p.G414W), ICOS (p.G60*), and IGHM (p.S19*) genes. We performed Sanger sequencing to validate pathogenic variants and check for allelic segregation in the family. Targeted NGS panel sequencing can be beneficial as a suitable diagnostic modality for diagnosing well-known monogenic PAD diseases (only 2–10% of PADs); however, screening only the coding regions of the genome may not be adequately powered to solve the pathogenesis of PAD in all cases. Deciphering the regulatory regions of the genome and better understanding the epigenetic modifications will elucidate the molecular basis of complex PADs.

     

Correction to: Primary antibody deficiencies in Turkey: molecular and clinical aspects

Immunologic Research -     

Neural Network Based Response Prediction of rTMS in Major Depressive Disorder Using QEEG Cordance

Objective

The combination of repetitive transcranial magnetic stimulation (rTMS), a non-pharmacological form of therapy for treating major depressive disorder (MDD), and electroencephalogram (EEG) is a valuable tool for investigating the functional connectivity in the brain. This study aims to explore whether pre-treating frontal quantitative EEG (QEEG) cordance is associated with response to rTMS treatment among MDD patients by using an artificial intelligence approach, artificial neural network (ANN).

Methods

The artificial neural network using pre-treatment cordance of frontal QEEG classification was carried out to identify responder or non-responder to rTMS treatment among 55 MDD subjects. The classification performance was evaluated using k-fold cross-validation.

Results

The ANN classification identified responders to rTMS treatment with a sensitivity of 93.33%, and its overall accuracy reached to 89.09%. Area under Receiver Operating Characteristic (ROC) curve (AUC) value for responder detection using 6, 8 and 10 fold cross validation were 0.917, 0.823 and 0.894 respectively.

Conclusion

Potential utility of ANN approach method can be used as a clinical tool in administering rTMS therapy to a targeted group of subjects suffering from MDD. This methodology is more potentially useful to the clinician as prediction is possible using EEG data collected before this treatment process is initiated. It is worth using feature selection algorithms to raise the sensitivity and accuracy values.     

TREATMENT OF ALPHA-FETOPROTEIN SECRETING HEPATOBLASTOMA BY RESPONSE OF SERUM ALPHA-FETOPROTEIN LEVELS: A New Concept

Hepatoblastoma, thecommonest primary malignant livertumorin infants and children, is usually associated with elevated serum alpha-fetoprotein (AFP) levels. The authors sought to determine if AFP levels can be used to modify treatment, thereby avoiding the wait for formal imaging studies and prolonged suboptimal treatment and limiting the use of effective but toxic chemotherapy. From April 1984 to December 1997, 8 children were diagnosed with AFP-secreting hepatoblastoma. Serum AFP levels were measured weekly. If AFP levels failed to improve, or increased on at least 2 successive examinations, the chemotherapy protocol was changed. When an excellent response was achieved, less toxic chemotherapy was substituted. Six patients (75%) were disease-free for at least 2 years, some with high-risk or metastatic disease. Two patients died. Six of the 7 nonmetastatic patients (86%) remain disease-free (only one had a resectable tumor). Chemotherapy changes resulted in reduced AFP levels in 7 patients. This study supports the use of AFP monitoring to modify treatment in hepatoblastoma responding to therapy with less toxic drugs and the use of nonstandard therapy when suboptimal responses are obtained.     

An unusual co-presentation of rhinolithiasis and squamous cell carcinoma in the nasal cavity

Rhinoliths are nasal stones that result from mineralisation of salts around an endogenous or exogenous nidus within the nasal cavity. They are uncommon nasal masses and usually unilateral and single, situated in the floor of the nose. The patient typically presents with nasal obstruction, facial pain and foul-smelling nasal secretion. To the best of our knowledge, the occurrence of squamous cell carcinoma with rhinolithiasis has not been previously reported in the English-language literature. In this article, we present a 63-year-old man, who had unilateral rhinolithiasis with squamous cell carcinoma within the nasal cavity.     

A new surgical technique for adenoid cystic carcinoma involving tracheal carina

Reported is the successful treatment of a 24-year-old male with adenocystic carcinoma involving the tracheal carina, in which the tumor extended along the right main bronchus across the orifice of the right upper lobe. The patient underwent a carinal resection plus right upper lobectomy and reconstruction of the carina, resulting in neither anastomotic complication nor recurrence of disease during 28 months of follow-up.     

Normative data and factorial structure of the Turkish version of the Temperament and Character Inventory

Cloninger's dimensional psychobiological model of personality accounts for both normal and abnormal variation in 2 major personality components: temperament and character. Here, we examined the psychometric properties of the Turkish version of the Temperament and Character Inventory (TCI) in a healthy Turkish population, obtaining normative data for the Turkish TCI. The study was conducted in healthy volunteers at both Karadeniz Technical University School of Medicine and Atatürk University School of Medicine (n = 683). The Turkish sample had significantly lower mean scores on Novelty Seeking and Reward Dependence and higher mean scores on Harm Avoidance than the American sample. The Turkish sample had significantly lower scores on Self-Directedness, Cooperativeness, and Self-Transcendence. Self-Directedness and Harm Avoidance, Cooperativeness and Reward Dependence, and Cooperativeness and Self-Directedness were intercorrelated. The Cronbach coeficients were between 0.60 and 0.85 on temperament dimensions, and between 0.82 and 0.83 on character dimensions. The lowest Cronbach coefficients were found in Reward Dependence (0.60) and Persistence (0.62). A principal axis factor analysis with a 4-factor solution revealed the highest loadings on Novelty Seeking and Harm Avoidance and relatively weaker loadings on Reward Dependence and Persistence. A 3-factor solution for character subscales indicated the highest loadings on Cooperativeness and Self-Transcendence. The factorial structure was consistent with Cloninger's 7-factor model of personality, and test-retest indicated a good stability of scores over time. The reliability and factorial validity of the Turkish version of the TCI are therefore supported.     

Effects of radiofrequency catheter ablation on myocardial performance index and plasma NT-Pro-BNP levels in patients with Wolff-Parkinson-White syndrome

Background: The myocardial performance index (Tei index) is an echocardiographic index of combined systolic and diastolic functions. Brain natriuretic peptide (BNP) and its biologically inactive fragment N-terminal pro-BNP (NT-pro-BNP) are secreted by the heart in response to myocardial stretch. In this study, we investigated Tei index and NT-pro-BNP levels in patients with Wolff-Parkinson-White (WPW) syndrome before and after radiofrequency catheter ablation therapy (RFCA).
Methods: Thirty patients (19 males, 11 females, aged 35.5 ± 14.4 years) with WPW syndrome were enrolled in this study. Echocardiographic examination was performed before and 24 hours after RFCA. Tei index was calculated using Doppler echocardiography. Blood samples were taken before and 24 hours after RFCA to detect levels of NT-pro-BNP. Results: Although isovolumic contraction time (IVCT) and isovolumic relaxation time (IVRT) did not change, aortic ejection time (ET) was decreased after RFCA (276 ± 22 ms vs 254 ± 30 ms, P < 0.01). So Tei index was significantly higher in postablation period (0.36 ± 0.11 vs 0.42 ± 0.21, P < 0.05). NT-pro-BNP levels did not change significantly after RFCA. Conclusions: We demonstrated that restoration of normal atrioventricular conduction by RFCA, leads to increase in Tei index but does not effect plasma NT-pro-BNP levels .     

Impact of early tirofiban administration on myocardial salvage in patients with acute myocardial infarction undergoing infarct-related artery stenting

BACKGROUND/AIMS: The timing of GpIIb/IIIa inhibitor administration may be important in achieving early epicardial and myocardial reperfusion. We evaluated the effect of early tirofiban on myocardial salvage and cardiovascular outcome in patients with acute myocardial infarction (AMI) undergoing infarct-related artery stenting. METHODS: Patients (n = 66) with a first AMI presenting <6 h from onset of symptoms were randomized to either early administration of tirofiban in the emergency room (n = 32) or later administration in the catheterization laboratory (n = 34) (tirofiban bolus dose of 10 microg/kg, followed by 0.15 microg/kg for 24 h). The primary end-point was the degree of myocardial salvage, determined by means of serial scintigraphic studies with technetium-99m sestamibi. Thirty-day major adverse cardiac events were also assessed. RESULTS: There were no significant differences in patient characteristics or in their presentation. The mean door-to-balloon time was similar in both groups (43 +/- 12 and 53 +/- 9 min, p = 0.08). The early and late treatment groups received tirofiban 18 +/- 4 and 52 +/- 10 min after admission, respectively. Angiographic analysis revealed a higher initial frequency of TIMI grade 3 flow in the early group (31% vs. 12%, p = 0.04). Procedural success was achieved in all patients. Myocardial risk area were comparable between early and late treatment groups (35.6 +/- 12.2% vs. 39.3 +/- 14.0%, p = 0.6). Scintigraphic outcomes demonstrated a significant reduction in the final infarction size (11.8 +/- 5.2% vs. 22.4 +/- 6.2%, p = 0.01), and improvement in salvage index (0.68 +/- 0.22 vs. 0.44 +/- 0.18, p = 0.003) in favor of the early tirofiban group. The thirty-day composite end-point of death, recurrent MI or rehospitalization also favored the early group (6% early, 15% late, p = 0.06). CONCLUSION: Early tirofiban administration enhanced the degree of myocardial salvage and clinical outcome in patients with AMI undergoing infarct-related artery stenting.