Bacterial and fungal communities in chronic rhinosinusitis with nasal polyps.

OBJECTIVE: Multiple inflammatory mechanisms dynamically interact in the development of chronic rhinosinusitis with nasal polyps (CRSwNP). Disruption of the relationship between host and environmental factors on the mucosal surface leads to the development of inflammation. Microorganisms constitute the most important part of environmental factors. METHODS: 28 volunteers (18 CRSwNP patients and 10 healthy individuals) were included in the study. Eight patients were recurrent nasal polyposis cases, and the remaining were primary cases. Swab samples were taken from the middle meatus under endoscopic examination from all participants. After DNA extraction, a library was created with the Swift Amplicon 16S + ITS kit and sequenced with Illumina Miseq. Sequence analysis was performed using QIIME, UNITE v8.2 database for ITS and Silva v138 for 16S rRNA. RESULTS: The predominant bacteria in all groups were Firmicutes, Proteobacteria, Actinobacteria as phyla and Staphylococcus, Corynebacterium, Sphingomonas as genera. Comparison of bacterial communities of CRSwNP patients and control group highlighted Corynebacterium, as the differentiating taxa for control group and Streptococcus, Moraxella, Rothia, Micrococcus, Gemella, and Prevotella for CRSwNP patients. The predominant fungal genus in all groups was Malassezia. Staphylococcus; showed a statistically significant negative correlation with Dolosigranulum. Corynebacterium had a positive correlation with Anaerococcus, and a negative correlation with Neisseria, Prevotella, Fusobacterium and Peptostreptococcus. CONCLUSION: Nasal microbiome of CRSwNP patients shows greater inter-individual variation than the control group. Corynebacterium is less abundant in patients with CRSwNP compared to the control group. Malassezia is the predominant fungus in the nasal cavity and paranasal sinuses and correlates positively with the abundance of Corynebacterium.

New cases of recently described Thauvin-Robinet-Faivre syndrome with a novel homozygous FIBP gene variant.

Thauvin-Robinet-Faivre syndrome (#617107) is a rare autosomal recessive overgrowth syndrome characterized by intellectual disability, facial dysmorphism, macrocephaly, and variable congenital malformations. It is caused by homozygous or compound heterozygous FIBP gene mutations. The FIBP gene is located on the 11q13.1 region and codes the acidic fibroblast growth factor intracellular binding protein, which is involved in the fibroblast growth factor (FGF) signaling pathway. FGF signaling is required for neurogenesis and neuronal precursor proliferation. The FGF controls cell proliferation, differentiation, and migration in embryonic development and in adult life. Overgrowth syndromes consist of a wide spectrum disorders characterized by prenatal and postnatal excess growth in weight and length, often associated malformations, intellectual disability, and neoplastic predisposition. Embryonic tumors are especially common in these syndromes. Thauvin-Robinet-Faivre syndrome is a recently described overgrowth syndrome with typical facial dysmorphic and clinical features. To date, only four patients have been reported with this disorder. Herein, two new cases of Thauvin-Robinet-Faivre syndrome are reported with overgrowth, intellectual disability, typical dysmorphic signs in one dysplastic kidney, and a novel homozygous FIBP gene variant. Exome sequencing analysis showed that both affected siblings share the same homozygous c. 412-3_415dupCAGTTTG FIBP gene variant. Reporting two new cases with this rare autosomal recessive overgrowth syndrome with a novel FIBP gene variant will support and expand the clinical spectrum of Thauvin-Robinet-Faivre syndrome. Also discussed will be the function of FIBP in tumorigenesis and the possible renal tumor susceptibility in heterozygous carriers will be emphasized.

Autosomal recessive otospondylo-mega-epiphyseal dysplasia: comprehensive clinical review of a pediatric cohort.

Autosomal recessive otospondylo-mega-epiphyseal dysplasia (OSMEDB) is characterized by short stature with short limbs, dysmorphic facial features, and hearing loss, which is caused by biallelic, loss-of-function, variants in the COL11A2 gene. Geno-phenotypic data from the medical records of eight affected individuals from five unrelated families was abstracted, recorded in an Excel spreadsheet and analyzed using simple frequency analysis. Either short femora or short extremities with or without other ultrasonographic abnormalities were demonstrated in five patients antenatally. The mean height was -2.29 SDS. Pectus deformity, including either chest asymmetry or pectus excavatum, was present in five patients. Bilateral hearing loss was verified in all patients. Severe speech delay and learning disabilities were present in two patients whose deafness was realized after the age of 12 months. Four novel loss-of-function variants in COL11A2 were found in this cohort. We present novel geno-phenotypic findings in a pediatric cohort with OSMEDB. The age of manifestation of short stature was variable, ranging from birth to middle childhood, and the severity of short stature varied even within the same family. Hearing loss may not be evident in the neonatal period and manifest later in OSMEDB. Intermittent hearing tests should be performed for early intervention of neurolinguistic delay and learning disabilities.

A Disseminated Echinococcosis Patient with Five Years Survival from Turkey: A Case Report.

Echinococcosis is a parasitic disease characterized by cysts in especially liver and lung. We report a long-term survival of a 44-year-old female patient with disseminated echinococcal disease involving the brain, lung, liver, spleen, kidney, mediastinum, thyroid gland, parotid gland, pancreas, peritoneum, rectus muscle, pararenal area, left thigh, skin and breast tissue from Turkey in 2016.

Acromesomelic dysplasia-Maroteaux type, nine patients with two novel NPR2 variants.

OBJECTIVES: Acromesomelic dysplasia, type Maroteaux, is an autosomal recessive skeletal dysplasia caused by biallelic loss of function variations of NPR2, which encodes a cartilage regulator C-type natriuretic peptide receptor B. NPR2 variations impair skeletal growth. It is a rare type of dwarfism characterized by shortening of the middle and distal segments of the limbs with spondylar dysplasia. METHODS: We performed detailed clinical and radiological evaluation and sequence analysis for NPR2. RESULTS: Herein, we report nine patients from eight families with two novel NPR2 pathogenic variants. CONCLUSIONS: This study describes typical clinical phenotypes of Maroteaux type acromesomelic dysplasia, and enriches the variant spectrum of NPR2 by reporting one nonsense and one missense novel variant. We emphasize the importance of detailed clinical evaluation before genetic testing in diagnosing rare skeletal disorders.

Risk factors for linezolid-associated thrombocytopenia and negative effect of carbapenem combination.

INTRODUCTION: Linezolid is a synthetic antimicrobial agent with a broad spectrum of activity against virtually all Gram-positive bacteria. Although linezolid is generally well tolerated, the prolonged use of linezolid can lead to myelosuppression, including neutropenia, thrombocytopenia, and anemia. The aim of this study was investigating the risk factors for thrombocytopenia in patients who received linezolid therapy. METHODOLOGY: This retrospective study was performed on patients who received linezolid therapy between July 2007 and December 2017. Thrombocytopenia was defined as either a platelets count of < 100×109/L or a 25% reduction from the baseline platelet count. RESULTS: A total of 371 patients, (198 (53%) male and 173(47%) female were included into the study. Mean duration of therapy was 12.81 ± 5.19 days. Linezolid-induced thrombocytopenia was detected in a total of 111 patients. Using the univariate analysis advanced sex, serum urea concentration, baseline platelet level and low eGFR value were found to be risk factors for linezolid associated thrombocytopenia (p < 0.05). According to a multivariate analysis, patients undergoing carbapenem treatment combination therapy (p = 0.003) and with a baseline platelet level of < 200×109/L (p = 0.00) were found to have a high risk of developing thrombocytopenia. CONCLUSIONS: Several factors may influence of linezolid associated thrombocytopenia. Platelet count should be monitored during therapy and thrombocytopenia should be kept in mind in patients with baseline platelet level of < 200×109/L, low eGFR, linezolid-carbapenem combination therapy.

First cardiac manifestation of hypotonia-cystinuria syndrome.

Hypotonia-cystinuria syndrome is a very rare autosomal recessive contiguous gene deletion syndrome of PREPL and SLC3A1 at 2p21 with neuromuscular and neuroendocrinologic presentation. We report a two-year-six-month-old affected female infant and her five-month-old affected brother with a novel homozygous deletion in SLC3A1 and PREPL gene. Both of siblings had mild facial dysmorphism, hypotonia, feeding problems, failure to thrive, developmental delay. She also had dilated cardiomyopathy which differ from other reported patients. Therefore cardiomyopathy may also be considered one of the features of hypotonia-cystinuria syndrome. With this case report, we present cardiac manifestation of hypotonia-cystinuria syndrome for the first time. Because of two siblings had hyperechogenic bowel in prenatal sonography, it might be a prenatal marker for HCS.

Evaluation of the increase in invasive device associated infections in cardiovascular surgical intensive care unit.

INTRODUCTION: Infections related to the use of invasive instruments leads to the risk of treatment difficulties, prolonged hospitalization, increased health care costs, and increased mortality and morbidity rates. The present study examines the results of an infection surveillance study that showed an increased incidence of infections related to the use of invasive instruments in the cardiovascular surgery intensive care unit of the Ankara Training and Research Hospital and mitigating measures were taken following the surveillance program. METHODOLOGY: Compared with previous surveillance data, an increase was observed in the incidence of infections related to the use of invasive instruments in cardiovascular surgery intensive care unit (CVS-ICU) during the first six months of 2014. A research team was formed comprising one infectious diseases and microbiology specialist, one cardiovascular surgeon, and two infection-control nurses. Patient data was collected. The compliance of the surgeons, nurses, and other health care professionals to the infection control measures was evaluated. RESULTS: The rate of ventilator-associated pneumonia was 8.20% and the rate of catheter-associated urinary tract infection was 4.47% in the CVS-ICU. There were missing or inadvertent practices regarding antibiotic prophylaxis, asepsis and antisepsis and isolation measures in patient preparation and patient care before and after the operations. The rate of inappropriate antibiotic as prolonged use was 72%. CONCLUSIONS: It is one of the basic tasks to take appropriate measures to prevent outbreaks of hospital infections. It is possible to prevent an outbreak of hospital infections only by the accurate analysis of data and establishing strict infection control procedures.

Clinical delineation of a subtype of frontonasal dysplasia with creased nasal ridge and upper limb anomalies: Report of six unrelated patients.

Frontonasal dysplasias are rare congenital malformations of frontonasal process-derived structures, characterized by median cleft, nasal anomalies, widely spaced eyes, and cranium bifidum occultum. Several entities of syndromic frontonasal dysplasia have been described, among which, to date, only a few have identified molecular bases. We clinically ascertained a cohort of 124 individuals referred for frontonasal dysplasia. We identified six individuals with a similar phenotype, including one discordant monozygous twin. Facial features were remarkable by nasal deformity with creased ridge and depressed or absent tip, widely spaced eyes, almond-shaped palpebral fissures, and downturned corners of the mouth. All had apparently normal psychomotor development. In addition, upper limb anomalies, frontonasal encephalocele, corpus callosum agenesis, choanal atresia, and congenital heart defect were observed. We identified five reports in the literature of patients presenting with the same phenotype. Exome sequencing was performed on DNA extracted from blood of two individuals, no candidate gene was identified. In conclusion, we report six novel simplex individuals presenting with a specific frontonasal dysplasia entity associating recognizable facial features, limb and visceral malformations, and apparently normal development. The identification of discordant monozygotic twins supports the hypothesis of a mosaic disorder. Although previous patients have been reported, this is the first series, allowing delineation of a clinical subtype of frontonasal dysplasia, paving the way toward the identification of its molecular etiology.

Polyposis deserves a perfect physical examination for final diagnosis: Bannayan-Riley-Ruvalcaba syndrome.

Hizarcioglu-Gülsen H, Kiliç E, Dominguez-Garrido E, Aydemir Y, Utine GE, Saltik-Temizel IN. Polyposis deserves a perfect physical examination for final diagnosis: Bannayan-Riley-Ruvalcaba syndrome. Turk J Pediatr 2017; 59: 80-83. Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare autosomal dominant inherited polyposis syndrome characterized by macrocephaly, lipomatosis, hemangiomatosis, intestinal polyposis and pigmented macules on penis. The mutation of the PTEN gene that is responsible for controlling cellular proliferation, migration and apoptosis clarifies the reason of tissue overgrowth in BRRS. Gastrointestinal tract involvement is seen 35-45% of the patients. Histologic features of polyps in BRRS resemble juvenile polyps. In this report, we describe a boy presenting with hematochezia and aggressive polyposis and finally was diagnosed as BRRS due to extra intestinal findings.

De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction.

Gorlin-Chaudhry-Moss syndrome (GCMS) is a dysmorphic syndrome characterized by coronal craniosynostosis and severe midface hypoplasia, body and facial hypertrichosis, microphthalmia, short stature, and short distal phalanges. Variable lipoatrophy and cutis laxa are the basis for a progeroid appearance. Using exome and genome sequencing, we identified the recurrent de novo mutations c.650G>A (p.Arg217His) and c.649C>T (p.Arg217Cys) in SLC25A24 in five unrelated girls diagnosed with GCMS. Two of the girls had pronounced neonatal progeroid features and were initially diagnosed with Wiedemann-Rautenstrauch syndrome. SLC25A24 encodes a mitochondrial inner membrane ATP-Mg/Pi carrier. In fibroblasts from affected individuals, the mutated SLC25A24 showed normal stability. In contrast to control cells, the probands' cells showed mitochondrial swelling, which was exacerbated upon treatment with hydrogen peroxide (H2O2). The same effect was observed after overexpression of the mutant cDNA. Under normal culture conditions, the mitochondrial membrane potential of the probands' fibroblasts was intact, whereas ATP content in the mitochondrial matrix was lower than that in control cells. However, upon H2O2 exposure, the membrane potential was significantly elevated in cells harboring the mutated SLC25A24. No reduction of mitochondrial DNA copy number was observed. These findings demonstrate that mitochondrial dysfunction with increased sensitivity to oxidative stress is due to the SLC25A24 mutations. Our results suggest that the SLC25A24 mutations induce a gain of pathological function and link mitochondrial ATP-Mg/Pi transport to the development of skeletal and connective tissue.

A Pulmonary Tuberculosis Case Presented with Tonsillar Involvement.

Tonsillar tuberculosis is a rare form of extra pulmonary tuberculosis. We reported a case with tonsillar tuberculosis secondary to pulmonary tuberculosis in this paper. A 26 year old, unimmunocompromised man admitted to head and neck surgery clinic with complaints of fever, throat ache and difficulty swallowing. The patient was consulted by infectious diseases clinic because of examination findings and his history. Asid fast basili was determined in tonsillar lesion smear, sputum and the patient was diagnosed as tonsillar and pulmonary tuberculosis. Antituberculous agents were started. Complaints of the patient were decreased and any adverse effect was developed. Treatment was completed in 9 months. In patients with long-term difficulty swallowing and fever, countries in which tuberculosis is prevalent, tonsillar tuberculosis should be considered, even if the patients were unimmunocompromised.

A case of fucosidosis type II: diagnosed with dysmorphological and radiological findings.

Fucosidosis is a rare autosomal recessive lysosomal storage disorder in which fucose-containing glycolipids, glycoproteins and oligosaccharides accumulate in tissues, as a result of a deficiency of α-L-fucosidase. In this report we describe clinical, dysmorphological and radiological findings of a boy with this disorder. Developmental delay, skeletal deformities and mild coarsening of the face began at two years of age. Clinical signs typical for fucosidosis evolved over time. Psychomotor deterioration progressed slowly. At age 12, he could not walk without help; he was admitted to the hospital with intellectual disability, short stature and coarse facial features. A skeletal survey showed dysostosis multiplex. Cranial MRI demonstrated high intensities on the periventricular white matter and low intensities on the basal ganglia on T2-weighted images. Despite the absence of angiokeratoma on the skin, type II fucosidosis with clinical, dysmorphological and radiological signs was suspected. The diagnosis was established on the basis of severely decreased activity of α-L-fucosidase in the leukocytes. The natural history and specific dysmorphic and radiological findings should, even in the absence of angiokeratoma, assist in the differential diagnosis of this rare condition when lysosomal storage disorders are suspected, particularly in populations in which consanguineous marriages are common.

Striking hematological abnormalities in patients with microcephalic osteodysplastic primordial dwarfism type II (MOPD II): a potential role of pericentrin in hematopoiesis.

BACKGROUND: Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare primordial dwarfism that is similar to Seckel syndrome. Seckel syndrome is known to be associated with various hematological abnormalities; however, hematological findings in MOPD II patients have not been previously reported. The present study aimed to describe the hematological findings in a series of eight patients with MOPD II from a single center. MATERIALS AND METHODS: The study included eight patients with MOPD II that were analyzed via molecular testing, and physical and laboratory examinations. RESULTS: Molecular testing showed that seven of the eight patients had pericentrin (PCNT) gene mutations. Hematological evaluation showed that 7 (87.5%) patients had thrombocytosis, 6 (75%) had leukocytosis, 5 (62.5%) had both leukocytosis and thrombocytosis, and 2 (25%) had anemia. CONCLUSIONS: We report leukocytosis and thrombocytosis as a common hematologic abnormality in patients with MOPD II. The present findings may improve our understanding of the potential function of the PCNT gene in hematopoietic cell proliferation and differentiation.

The diagnostic challenge of progressive pseudorheumatoid dysplasia (PPRD): a review of clinical features, radiographic features, and WISP3 mutations in 63 affected individuals.

Progressive pseudorheumatoid dysplasia (PPRD) is a genetic, non-inflammatory arthropathy caused by recessive loss of function mutations in WISP3 (Wnt1-inducible signaling pathway protein 3; MIM 603400), encoding for a signaling protein. The disease is clinically silent at birth and in infancy. It manifests between the age of 3 and 6 years with joint pain and progressive joint stiffness. Affected children are referred to pediatric rheumatologists and orthopedic surgeons; however, signs of inflammation are absent and anti-inflammatory treatment is of little help. Bony enlargement at the interphalangeal joints progresses leading to camptodactyly. Spine involvement develops in late childhood and adolescence leading to short trunk with thoracolumbar kyphosis. Adult height is usually below the 3rd percentile. Radiographic signs are relatively mild. Platyspondyly develops in late childhood and can be the first clue to the diagnosis. Enlargement of the phalangeal metaphyses develops subtly and is usually recognizable by 10 years. The femoral heads are large and the acetabulum forms a distinct "lip" overriding the femoral head. There is a progressive narrowing of all articular spaces as articular cartilage is lost. Medical management of PPRD remains symptomatic and relies on pain medication. Hip joint replacement surgery in early adulthood is effective in reducing pain and maintaining mobility and can be recommended. Subsequent knee joint replacement is a further option. Mutation analysis of WISP3 allowed the confirmation of the diagnosis in 63 out of 64 typical cases in our series. Intronic mutations in WISP3 leading to splicing aberrations can be detected only in cDNA from fibroblasts and therefore a skin biopsy is indicated when genomic analysis fails to reveal mutations in individuals with otherwise typical signs and symptoms. In spite of the first symptoms appearing in early childhood, the diagnosis of PPRD is most often made only in the second decade and affected children often receive unnecessary anti-inflammatory and immunosuppressive treatments. Increasing awareness of PPRD appears to be essential to allow for a timely diagnosis.

Medical management of moyamoya disease and recurrent stroke in an infant with Majewski osteodysplastic primordial dwarfism type II (MOPD II).

UNLABELLED: We report an infant diagnosed with Majewski osteodysplastic primordial dwarfism type II at age 8 months, who experienced cerebrovascular morbidities related to this entity. Molecular analysis identified c.2609+1 G>A, intron 14, homozygous splice site mutation in the pericentrin gene. At age 18 months, she developed recurrent strokes and hemiparesis. Brain magnetic resonance imaging and magnetic resonance angiography showed abnormal gyral pattern, cortical acute infarcts, bilateral stenosis of the internal carotid arteries and reduced flow on the cerebral arteries, consistent with moyamoya disease. In Majewski osteodysplastic primordial dwarfism type II, life expectancy is reduced because of high risk of stroke secondary to cerebral vascular anomalies (aneurysms, moyamoya disease). Periodic screening for vascular events is recommended in individuals with Majewski osteodysplastic primordial dwarfism type II every 12-18 months following diagnosis. Our patient was medically managed with low molecular weight heparin followed with aspirin prophylaxis, in addition to carbamazepine and physical rehabilitation. CONCLUSION: We report an infant with moyamoya disease and recurrent stroke presenting 10 months after diagnosis (at age 18 months), and discuss the outcome of nonsurgical medical management. The presented case is the second youngest case developing stroke and moyamoya disease.

Novel mutations in GALNT3 causing hyperphosphatemic familial tumoral calcinosis.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is known to be caused by mutations in at least three genes: FGF23, GALNT3 and KL. Two families with two affected members suffering from HFTC were scrutinized for mutations in these candidate genes. We identified in both families homozygous missense mutations affecting highly conserved amino acids in GALNT3. One of the mutations is a novel mutation, whereas the second mutation was reported before in a compound heterozygous state. Our data expand the spectrum of known mutations in GALNT3 and contribute to a better understanding of the phenotypic manifestations of mutations in this gene.

[The effect of permanent ostomy on body image, self-esteem, marital adjustment, and sexual functioning]. / Kalici Ostomi Ameliyatinin Beden Algisi, Benlik Saygisi, Es Uyumu ve Cinsel Islevler Uzerine Etkisi.

OBJECTIVE: The aim of this study was to investigate the effects of permanent ostomy on body image, sexual functioning, self-esteem, and marital adjustment. METHOD: SCID-I outpatient forms were administered to 52 subsequent patients that underwent permanent colostomy or ileostomy operations, and 40 of them that did not fit any of the diagnostic criteria for psychiatric disorders were then administered a sociodemographic data questionnaire, and the Body Image Scale, Rosenberg Self-Esteem Scale, Dyadic Adjustment Scale, and Golombok Rust Sexual Functions scale. The control group consisted of 20 age- and gender-matched healthy volunteers. RESULTS: Body Image, Rosenberg Self-Esteem, and Dyadic Adjustment Scale scores were higher in permanent ostomy patients compared to controls, indicating more ostomy-related disturbance. Sexual functions were found to be impaired as well, except impotence and rapid ejaculation parameters. Complaints of anorgasmia were more frequent among female colostomy patients. Body image, and the touch, communication, and frequency parameters of sexual functioning were less disturbed in male patients than in females. Female patients with a psychiatric history experienced vaginismus problems more frequently. Patients with a history early childhood separation from parents had lower self-esteem scores and more frequently avoided sexual activity. Following ostomy surgery, the frequency of male impotence decreased over time. CONCLUSION: Permanent ostomy causes impairment in perceived body image, dyadic adjustment, and sexual functioning.