Treatment of tuberous sclerosis complex manifestations in children with mTOR inhibitors.

PURPOSE: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder that affects multiple organ systems. Mutations in the TSC1 and TSC2 genes result in the constitutive hyperactivation of the mammalian target of rapamycin (mTOR) pathway, contributing to the growth of benign tumors or hamartomas in various organs. Due to the implication of mTOR pathway dysregulation in the disease pathology, increasing evidence supports the use of mTOR inhibitors for treating multiple manifestations of TSC. METHODS: In this study, we conducted a retrospective analysis of clinical findings and treatment data from 38 patients diagnosed with tuberous sclerosis who were followed up in the Pediatric Oncology Clinic between 2010 and 2020. We collected information on patients' ages, genders, affected sites, familial history, imaging findings, presence of tumors, and treatments. RESULTS: Among the patients, nine individuals with TSC manifestations were treated with mTOR inhibitors. Specifically, everolimus was successfully administered to five patients with inborn cardiac rhabdomyoma causing hemodynamic impairment. In addition, two patients with refractory seizures received everolimus in combination with anti-epileptic drugs. A patient with renal angiomyolipomas larger than 3 cm was treated with everolimus, while a patient with extensive facial angiofibroma received topical sirolimus. All patients tolerated the mTOR inhibitors well, and the side effects were deemed acceptable. CONCLUSION: The utilization of mTOR inhibition in TSC is expected to become more prevalent in clinical practice, as current research is anticipated to provide a better understanding of the therapeutic roles of these treatments in TSC.

[Evaluation of the Epidemiological, Clinical and Radiological Features of Pneumonia Cases Caused by Mycoplasma pneumoniae in Childhood]. / Çocukluk Çaginda Mycoplasma pneumoniae'nin Etken Olarak Saptandigi Pnömoni Olgularinin Epidemiyolojik, Klinik ve Radyolojik Özelliklerinin Degerlendirilmesi.

The current study aimed to investigate the clinical, laboratory and radiological findings of the pneumonia cases in children that were confirmed as M.pneumoniae by polymerase chain reaction (PCR) testing and to reveal the factors that can be decisive in the diagnosis. Seventy-seven children were included in this study. The median age of the patients was 31 months (1 month-17 years 4 months). The 63.6% of the patients were younger than five years of age, 53.2% were girls and 46.8% were boys. During the eight-year research period, the frequency of M.pneumoniae in the patients hospitalized with the diagnosis of pneumonia was found to be 3.1%. The rate of M.pneumoniae as the underlying factor of pneumonia was found to be statistically significantly lower in patients aged 0-60 months compared to the patients aged 61-216 months. In patients with M.pneumoniae accompanied by viruses, the age group was more likely to between 0-60 months. The most common symptoms were cough (96.1%) and fever (74%). Physical examinations revealed that 70.1% of the patients had rales, 63.6% had tachypnea, 45.5% had oropharyngeal hyperaemia, 35.1% had subcostal-intercostal retraction, 31.2% had long expiration period, 26% had rhonchus, 24.7% had decrease in breath sounds, 15.6% had cervical lymphadenopathy, 13% had tachycardia, 3.9% had otitis media, 3.9% had tonsil hypertrophy and 2.6% had a maculopapular rash. The rate of hypoxemia was found to be 42.2%. When the physical examination findings of patients with only M.pneumoniae detected in multiplex PCR analysis and those with accompanying viruses in M.pneumoniae were compared, tachypnea, oropharyngeal hyperemia and decreased breath sounds were found to be statistically significantly higher in patients with M.pneumoniae only. Retraction was detected more frequently in patients with accompanying viruses. When the laboratory results of the patients were evaluated according to age, leukocytosis was detected in only 18.2% of the patients, while the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were found to be high in 75% and 85.7% of the patients, respectively. In the multiplex PCR analysis, the CRP values of the patients with only M.pneumoniae were found to be higher than the patients with accompanying viruses. M.pneumoniae was accompanied by viruses at the rate of 40.3%. The most common accompanying viruses were rhinovirus, adenovirus, bocavirus and metapneumovirus. The 55.8% of the patients had lobar-segmental consolidation, 46.8% had parahilar-peribronchial thickening, 18.2% had atelectasis, 11.7% had pleural effusion, 9.1% had increase in reticulonodular density, 6.5% had lymphadenopathy whereas no abnormality was observed in 5.2% of them. No diffuse interstitial involvement was recorded. The CRP value of the patients who had lobar segmental consolidation which was detected through chest X-rays were statistically higher than those without consolidation. In multiplex PCR analysis, the rate of parahilar-peribronchial thickening detected in chest X-ray findings was found to be higher in patients with M.pneumoniae accompanied by viruses compared to those with only M.pneumoniae. The rate of the patients who were given empirical antibiotics against atypical agents was 45.5%. The rate of empirically administered antibiotic treatment for atypical agents after being hospitalization was higher in patients diagnosed with only M.pneumoniae compared to patients with M.pneumoniae and viruses. One patient (1.3%) died. As there are no typical clinical, laboratory or radiological findings specific to M.pneumoniae pneumonia, all of the findings should be assessed as a whole to establish a diagnosis. Besides, for the detection of M.pneumoniae, diagnostic tests which are cost effective, with rapid results and are capable of distinguishing colonisation from active infection should be developed.

Cytogenetic profile of adult AML patients in Turkey: a single center study with comprehensive comparison with literature.

Background: Cytogenetic findings are important prognostic factors in acute myeloid leukemia. Large systematic data about chromosomal characteristics of Turkish AML patients have not been reported to date. Objectives: The karyotypic profiles of 157 adult AML patients were evaluated retrospectively and compared with other reports from different populations. Methods: Cytogenetics analyses were performed on bone marrow samples using G-banding. Patients were categorized according to their cytogenetic results into four groups with the addition of a normal karyotyped group to the favorable, intermediate and adverse groups of European Leukemia Network. Results: Cytogenetic analyses were carried out successfully in 138 patients (88%). Abnormal karyotypes were found in 79 (57.2%) patients of which 13 (9.4%) were in favorable, 37 (26.8%) in intermediate and 29 (21%) in adverse groups. t(8;21) (5%) was the most common favorable abnormality while monosomal karyotypes (15.9%) in adverse group. Conclusion: This single center study is the most comprehensive study about the cytogenetic profile of acute myeloid leukemia in Turkey with comparison of other population-based studies. While there were similarities and differences with different publications, our results did not show a marked tendency to the findings of any specific geographic region.

Herlyn-Werner-Wunderlich Syndrome: Sonographic and Magnetic Resonance (MR) Imaging Findings of This Rare Urogenital Anomaly.

BACKGROUND: Herlyn-Werner-Wunderlich syndrome is a rare congenital urogenital anomaly characterised by uterus didelphys with blind hemivagina and ipsilateral renal agenesis. Children usually have progressive pelvic pain after menarche, palpable mass due to hemihaemato(metro)colpos or pelvic inflammatory disease. The diagnosis usually requires a suspicion of this rare genitourinary syndrome. CASE REPORTS: We present ultrasonography and MR imaging findings of this rare anomaly in two cases. CONCLUSIONS: Early recognition of this rare syndrome can lead to an immediate, proper surgical intervention and is necessary to prevent complications and preserve future fertility. Ultrasound and MR imaging findings can collectively delineate uterine morphology, indicate the absence of ipsilateral kidney and show obstructed hemivagina.

Analysis of Chromosome 3, 7 and 8 Centromeric Regions in Bronchial Lavage Specimens by FISH.

OBJECTIVES: Multiple genetic changes are observed in malignant tumors but are rare or absent in benign conditions. Aneuploidy is the most common feature of solid tumors including lung cancer and diagnosis of malignant tumors is possible through detection of aneuploidy. The aim of this study was to investigate chromosomal abnormalities in cells from non-small cell lung cancer patients obtained bronchoscopically and to evaluate the suitability of fluorescence in situ hybridization (FISH). MATERIAL AND METHODS: Bronchial lavage samples of 17 non-small cell lung cancer (NSCLC) patients were evaluated with four-color FISH using deoxyribonucleic acid (DNA) probes specific for the centromere regions of chromosomes 3, 7 and 8. tested specimens were first hybridized with probes, then visualized under fluorescence microscobe and captured with device's camera. RESULTS: High number of aneuploidic cells were detected in all the samples. Increased or decreased abnormal copies or chromosomes 3, 7 and 8 were obserced in all the 17 patients. Aneuploidy of chromosome 3 (21.35%) was higher than those of chromosome 7 (9.06%) and chromosome 8 (15.47%). Moreover, our results were significant for monosomy and trisomy of chromosome 3, trisomy of chromosome 7, nullisomy, monosomy and trisomy of, chromosome 8 (p< 0.05). CONCLUSION: It has been observed that FISH is a useful technique for detection of aneuploidy in bronchial lavage samples obtained by bronchoscopy. Interphase cells were evaluated without cell culturing with this method and high number of tumor cells were enumerated rapidly. Our study has demonstrated that, FISH technique may be used successfully in detection of chromosome number abnormalities in NSCLC patients and may facilitate evaluation of genetic abnormalities.

Variant Philadelphia translocations with different breakpoints in six chronic myeloid leukemia patients.

OBJECTIVE: The Philadelphia (Ph) chromosome, consisting of the t(9;22)(q34;q11) translocation, is observed in ~90% of patients with chronic myeloid leukemia (CML). Variant Ph translocations are observed in 5%-10% of CML patients. In variant translocations 3 and possibly more chromosomes are involved. Herein we report 6 CML patients with variant Ph translocations. METHODS: Bone marrow samples were examined using conventional cytogenetic meth ods. Fluorescence in situ hybridization (FISH) with whole-chromosome paints and BCR-ABL 1D probes were used to confirm and/or complement the findings, and identify rearrangements beyond the resolution of conventional cytogenetic methods. RESULTS: Variant Ph translocations in the 6 patients were as follows: t(7;22)(p22;q11), t(9;22;15)(q34;q11;q22), t(15;22)(p11;q11), t(1;9;22;3)(q24;q34;q11;q21), t(12;22)(p13;q11), and t(4;8;9;22)(q11;q13;q34;q11). CONCLUSION: Among the patients, 3 had simple and 3 had complex variant Ph translocations. Two of the presented cases had variant Ph chromosomes not previously described, 1 of which had a new complex Ph translocation involving chromosomes 1, 3, 9, 22, and t(1;9;22;3)(q24;q34;q11;q21) apart from a clone with a classical Ph, and the other case had variant Ph translocation with chromosomes 4, 8, 9, and 22, and t(4;8;9;22)(q11;q13;q34;q11) full complex translocation. Number of studies reported that some patients with variant Ph translocation were poor responders to imatinib. All of our patients with variant Ph translocations had suboptimal responses to imatinib, denoting a poor prognosis also. Variant Ph translocations may be important as they are associated with prognosis and therapy for CML patients.

Neuroblastoma in a dysmorphic girl with a partial duplication of 2p caused by an unbalanced translocation.

A 1-year-old female child with multiple dysmorphic features including microcephaly, hypertelorism, a short philtrum, low set ears, a narrow high arched palate, micrognathia and growth retardation was found to have a de novo chromosome abnormality including a partial duplication of the short arm of chromosome 2 and a partial deletion of the long arm of chromosome 17. The clinical features of the case shared many similarities to previous reports of trisomy 2p. Three years later, ecchymotic spots appeared around the left ocular region. Further clinical and pathological examination confirmed the diagnosis of a neuroblastoma. This is the first case of an unbalanced translocation, 46, XX, der (17), t (2; 17) (p23; q25), showing the development of a neuroblastoma in addition to the dysmorphic features. We suggest that trisomy 2p including the N-myc proto-oncogene may have predisposed the patient to the development of a neuroblastoma.

Looking for Our Ten Years Results for Coronary Heart Disease and Ischemic Stroke Group for the Standpoint of Haemostasis.

To evaluate the role the coagulation and fibrinolysis abnormalities in the pathogenesis of ischemic stroke of undetermined etiology, we assayed plasma concentration of fibrinopeptide-A and thrombin-antithrombin III complex, both sensitive markers for thrombin activation and fibrin formation, and D-dimer, a marker of plasmin activity and fibrinolysis. Hemostatic markers were measured in 32 patients with acute stroke and 20 patients with chronic stroke, and compared with 21 normal subjects. Fibrinopeptid-A and thrombin-antithrombin III complex levels were not elevated significantly, whereas the D-dimer level was markedly raised in acute (p<< 0.001) and chronic (p< 0.05) phases of ischemic stroke in comparison with the control group. Prolonged elevation of D-dimer concentration suggests that hemostatic abnormalities have a primary role in the pathogenesis of ischemic stroke. The measurement of D-dimer concentration may help to better decide the indications for therapy of the patients with ischemic stroke of undetermined etiology.