Comparison of clinical features of cystic fibrosis patients eligible but not on CFTR modulators to ineligible for CFTR modulators.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs target the underlying defect and improve CFTR function. They are a part of standard care in many countries, but not all patients are eligible for these drugs due to age and genotype. Here, we aimed to determine the characteristics of non-eligible patients for CFTR modulators in the CF registry of Turkey (CFRT) to highlight their clinical needs. METHODS: This retrospective cohort study included CF patient data from the CFRT in 2021. The decision of eligibility for the CFTR modulator was determined according to the 'Vertex treatment-Finder' on the Vertex® website. Demographic and clinical characteristics of patients were compared between eligible (group 1) and ineligible (group 2) groups for CFTR modulators. RESULTS: Among the study population (N = 1527), 873 (57.2%) were in group 1 and 654 (42.8%) were in group 2. There was no statistical difference between groups regarding sex, meconium ileus history, diagnoses via newborn screening, FEV1 z-score, CF-associated complications, organ transplant history, and death. Patients in group 2 had a higher incidence of pancreatic insufficiency (87.7% vs. 83.2%, p = .010), lower median height z-scores (-0.87 vs. -0.55, p < .001), lower median body mass index z-scores (-0.65 vs. -0.50, p < .001), longer days receiving antibiotics due to pulmonary exacerbation (0 [interquartile range, IQR: 0-2] vs. 0 [IQR: 0-7], p = 0.001), and more non-invasive ventilation support (2.6% vs. 0.9%, p = 0.008) than patients in group 1. CONCLUSION: The ineligible group had worse clinical outcomes than the eligible group. This highlights their need for life-changing drugs to improve clinical outcomes.

Bloodstream infections due to Trichosporon species in paediatric patients: Results from the first national study from Turkey.

BACKGROUND: Invasive Trichosporon infections are rarely seen opportunistic fungal infections in children and mainly affect immunocompromised patients. This multicenter retrospective study has rewieved the characteristics, risk factors, treatment modalities and outcomes of bloodstream infections caused by Trichosporon species in children diagnosed over the past ten years in Turkey. METHODS: The study was performed with the participation of 12 of 55 hospitals invited from Turkey. In each center, the patients with bloodstream infections caused by Trichosporon spp. between January 2010 and December 2020 were retrospectively ascertained and the results were reported to the study coordinator by means of a simple case report. Data were collected on patient demographics, underlying condition(s), treatment of.infections caused by Trichosporon spp, and 7 and 30- day mortality rates. RESULTS: A total of 28 cases with fungemia caused by Trichosporon spp. were included in the study. The most common underlying disease was paediatric cancers (39.3%). T. asahii infections were detected in 78.5 % (n=22) of patients. A various spectrum of antifungal treatment regimens were used including intravenous amphotericin B monotherapy in 35.7%, intravenous amphotericin B and voriconazole combination in 32.1% and intravenous voriconazole monotherapy in 28.6% of the patients. The overall mortality rate was 28.5 %. The mortality rates were 12.5% in the voricanozole, 30% in the amphotericin B and 33.3% in combined voriconazole -amphotericin B arms CONCLUSIONS: Invasive Trichosporon infections with an important impact of patients quality of life are almost related to underlying diseases with an overall mortality rate of 28.5%. Voriconazole was found to be associated with lower mortality rates when compared with other treatment regimens.

The first pediatric case of hemophagocytic lymphohistiocytosis secondary to Crimean-Congo haemorrhagic fever successfully treated with therapeutic plasma exchange accompanying ribavirin and intravenous immunoglobulin.

Although Crimean-Congo hemorrhagic fever (CCHF) is mild and self-limited in children, some patients may develop excessive bleeding, massive liver necrosis, and multiple organ failure associated with secondary hemophagocytic lymphohistiocytosis (HLH) induced by cytokine storm. Treatment of CCHF is mainly symptomatic and supportive. The efficacy of ribavirin, which is the only antiviral drug in the treatment of CCHF, remains controversial. Although therapeutic plasma exchange (TPE) has been shown to beneficial in small case series with primary and secondary HLH, there is no pediatric patient with HLH secondary to CCHF treated with TPE in the literature. In this report, we describe the first pediatric patient who was successfully recovered from HLH secondary to CCHF with ribavirin, intravenous immunoglobulin, and TPE.

Clinical features and accompanying findings of Pseudo-Bartter Syndrome in cystic fibrosis.

BACKGROUND: Pseudo-Bartter syndrome (PBS) is a rare complication of cystic fibrosis (CF) and there are limited data in the literature about it. We aimed to compare clinical features and accompanying findings of patients with PBS in a large patient population. METHODS: The data were collected from the Cystic Fibrosis Registry of Turkey where 1170 CF patients were recorded in 2017. Clinical features, diagnostic test results, colonization status, complications, and genetic test results were compared in patients with and without PBS. RESULTS: Totally 1170 patients were recorded into the registry in 2017 and 120 (10%) of them had PBS. The mean age of diagnosis and current age of patients were significantly younger and newborn screening positivity was lower in patients with PBS (P < .001). There were no differences between the groups in terms of colonization status, mean z-scores of weight, height, BMI, and mean FEV1 percentage. Types of genetic mutations did not differ between the two groups. Accompanying complications were more frequent in patients without PBS. CONCLUSION: PBS was detected as the most common complication in the registry. It could be due to warm weather conditions of our country. It is usually seen in younger ages regardless of mutation phenotype and it could be a clue for early diagnosis of CF.

Characteristics, diagnosis, and treatment modality of pediatric patients with cystic echinococcosis: a single centre experience.

Kaman A, Tanir G, Çakmakçi E, Demir P, Öz FN, Aydin Teke T, Metin Ö, Gayretli Aydin ZG, Karaman A. Characteristics, diagnosis, and treatment modality of pediatric patients with cystic echinococcosis: a single centre experience. Turk J Pediatr 2019; 61: 704-713. Cystic echinococcosis (CE) is among the most common zoonotic infections worldwide. Studies about CE are limited in childhood. The aim of this study was to evaluate clinical, radiological and laboratory characteristics of childhood CE at a tertiary care pediatric hospital. Medical records of children with CE were analyzed between January 2005 and January 2015. A total of 130 patients with a median age of 10.4 years (IQR= 7.2-years-13.2 years) were evaluated. The anatomic locations of cysts were as follows; liver (76.9%), lung (36.9%), spleen (6.2%), pelvic region (3.8%) and kidney (2.3%). The most common symptoms were abdominal pain and cough in the patients with liver cysts and lung cysts, respectively. The indirect hemagglutination (IHA) test positivity was 58%. Elevated serum total immunoglobulin E levels were detected in 59% of the patients. Fourty-four patients with liver CE, 33 patients with lung CE were treated surgically and 23 patients with liver CE were treated with percutaneous aspiration, injection and re-aspiration (PAIR) along with medical treatment. The recurrence was observed in five patients with liver CE. It was demonstrated that CE mainly involves liver but lung cysts are more frequently symptomatic and prone to be complicated than liver cysts in children. IHA test positivity together with abdominal ultrasonography are useful to diagnose liver CE but thorax CT is usually needed to diagnose lung CE. Liver cysts that are sized greater than 5 cm are more frequently treated with PAIR or surgery but smaller liver cysts can be treated medically.

[Screening of Corynebacterium diphtheriae, Corynebacterium ulcerans and Corynebacterium pseudotuberculosis in throat swab specimens of children with upper respiratory tract infections]. / Üst solunum yolu enfeksiyonu bulgulari ile basvuran çocuklarin bogaz sürüntü örneklerinde Corynebacterium diphtheriae, Corynebacterium ulcerans ve Corynebacterium pseudotuberculosis suslarinin arastirilmasi.

Although a significant decrease has been reported in the incidence of diphteria in many regions of the world following the routine diphtheria immunization programs, the emergence of new cases indicated that toxigenic strains are still circulating in the community. Diphtheria vaccine does not provide protection against asymptomatic carriage and colonization of non-toxigenic Corynebacterium diphtheriae. It is a known fact that invasive infections may arise from non-toxigenic C.diphtheriae strains that the non-toxigenic strains can become toxigenic strains leading to diphteria. It is also known that there is a risk of diphteria outbreaks due to decreased antitoxin level and inadequate adult immunization programs. In our country, there is no routine surveillance of toxigenic and non-toxigenic C.diphtheriae. In the present study we aimed to investigate the presence of C.diphtheriae, Corynebacterium ulcerans and Corynebacterium pseudotuberculosis in children presenting with the symptoms of upper respiratory tract infections that might be confused with those moderate diphteria, in order to highlight the requirement of microbiological surveillance and to create awareness about these microorganisms among public health experts, microbiologists and clinicians. Throat swab specimens were obtained from children who were admitted to the pediatric outpatient clinics, in Dr. Sami Ulus Obstectrics, Children Health and Diseases Educational and Research Hospital, with upper respiratory tract infections between 1 February 2016-22 March 2016. The specimens were inoculated in 5% sheep blood agar plates. The plates that were incubated in appropriate conditions, were evaluated for Group A beta hemolytic streptococcocci. Subsequently, culture plates were sent to the Public Health Institution of Turkey, National Respiratory Pathologens Reference Laboratories for the investigation of the presence of C.diphtheriae, C.ulcerans and C.pseudotuberculosis. The growth in each plate were collected with a sterile swab and inoculated in tryptic soy broth. Following 2 hours of incubation at 37oC, subcultures were inoculated in cystine-tellurite-blood agar (CTBA) and 5% sheep-blood agar plates; after an overnight incubation tellurite-reducing colonies were inoculated in Tinsdale agar plates. The suspected colonies with positive cystinase activity were identified by conventional methods and also with Coryne API (Biomerieux, France) systems. Toxicity tests (ELEK, PCR) were performed to investigate whether the C.diphtheriae strains were producing toxins. A total of 500 patients were involved in the study. Of these 260 (52%) were girls and 240 (48%) were boys with a mean age of 76 (range, 21-213) months. All patients except one were fully vaccinated with boosters. Most common presenting symptoms of the patients were fever (19.8%), sore throat (52.6%), cough (49.2%), tonsillar hyperemia (97.6%), presence of crypt (24.6%), and membrane over tonsils (1%). Group A beta-hemolytic streptococcocci were detected in the throat swab cultures of 66 (%13.2) patients. Genotypically toxin negative C.diphtheriae biovar gravis was identified in the throat swab cultures of 3 patients (2 girls and 1 boy). The tonsils were hyperemic and hypertrophic in all the patients with C.diphtheriae biovar gravis. C.ulcerans and C.pseudotuberculosis were detected in none of the patients. It is considered that similar regular cross-sectional studies or routine screening programs are expected to raise awareness about this forgotten microorganism both epidemiologically and microbiologically.

A Rare Pediatric Case of Neurocysticercosis Misdiagnosed As Brain Abscess.

Neurocysticercosis is a parasitic infection of the central nervous system caused by the larval stage of Taenia solium. Although this zoonotic infection is one of the major public health problems in some developing countries, it is extremely rare in Turkey. In this article, we present the case of a pediatric patient with neurocysticercosis who was misdiagnosed with brain abscess because of focal seizures in another hospital.

Evaluation of complicated and uncomplicated parapneumonic effusion in children.

Parapneumonic effusion (PPE) and empyema are most often seen as a complication of bacterial pneumonia and occasionally associated with atypical bacteria or viruses. The aims of this study were to describe and compare demographic characteristics, clinical, laboratory, microbiological findings and treatment modalities of patients with PPE and empyema. We retrospectively reviewed 116 pediatric patients with PPE and empyema. Seventy (60.3%) had pleural empyema and 46 patients (39.6%) had PPE. The median age of patients with empyema [72.0 months (IQR 68.0 months)] was lower than the patients with PPE [92.5 (IQR 80.0 months)] (p=0.003). Children in the empyema group had significantly more dyspnea symptoms than the children with PPE (p=0.022). Mean fever duration before hospitalization was similar in both groups. Streptococcus pneumoniae and group A streptococcus were the most common causes of empyema. All of the patients were treated with intravenous antibiotics. In addition to medical treatment, tube thoracostomy was performed in 59 of 70 (84.3%) patients in empyema group; 27 (45.8%) of them required intrapleural fibrinolysis also. In the presence of antibiotic treatment failure or in cases with moderate or large pleural effusion with loculations and clinical deterioration; it is necessary to perform drainage of the purulent fluid by tube thoracostomy, to add intrapleural fibrinolytics or to perform video-assisted thoracoscopic surgery (VATS), in order to enhance prompt recovery.

A case of Langerhans cell histiocytosis mimicking child abuse.

Langerhans cell histiocytosis is a rare non-malignant disease with clinical heterogeneity. The disease may present with various clinical findings and may imitate many other conditions. In this report we describe a 34-month-old girl who presented with chronic otitis and otorrhea, skull fracture, rash, vulvar edema, erythema and erosion in labia majors which initially suggested child abuse but the patient was diagnosed with Langerhans cell histiocytosis.

Assessment of bone turnover markers and bone mineral density in normal short boys.

AIM: To investigate whether there is a change in bone turnover-related biochemical markers and bone mineral density of children with constitutional delay of growth and puberty (CDGP) in the prepubertal period. METHODS: We measured serum calcium, phosphorus, alkaline phosphatase, parathormone, 25-OH vitamin D, osteocalcin, osteoprotogerin and urinary deoxypyridinoline levels (D-pyd), and bone mineral density (BMD) in 31 prepubertal boys with CDGP. These children were compared with 22 prepubertal boys with familial short stature (FSS) and 27 normal prepubertal boys. RESULTS: Urinary D-pyd was significantly high in CDGP group as compared to control group (p=0.010). Volumetric BMD did not significantly differ between CDGP, FSS, and control groups (p=0.450). Volumetric BMD and urinary D-pyd levels of FSS and control groups were similar. Mean or median levels of calcium, phosphorus, alkaline phosphatase, parathormone, and osteoprotegerin did not significantly differ between CDGP, FSS, and control groups. CONCLUSIONS: Our data suggest that prepubertal boys with CDPG have normal bone turnover. However, their significantly higher urinary D-pyd levels relative to those of FSS and control groups might be an indicator of later development of osteoporosis. Therefore, long-term follow-up studies monitoring bone mineral status of prepubertal boys with CDPG from prepuberty to adulthood are needed to better understand bone metabolism of these patients.

[Coexistence of Pulmonary Hydatid Cyst and Mycoplasma pneumoniae Pnömonia in a Child]. / Akciger Kist Hidatigine Eslik Eden Mycoplasma pneumonia Pnömonili Çocuk Olgu .

Hydatid cyst is a zoonotic disease and endemic in Turkey. The disease can involve any organ. The most common involved organ is lung in childhood. Hydatid cyst of lung may be asymptomatic or may be sometimes ruptured or infected. Secondary bacterial infections associated with the hydatid cyst are well known. A previously not reported pediatric case of hydatid cyst with Mycoplasma pneumoniae pneumonia is described in this report. It is emphasized that M. pneumoniae should be kept in mind as a cause of infected hydatid cyst which is unresponsive to beta-laktam antibiotics.

Miliary tuberculosis disease complicated by Pott's abscess in an infant: Seven year follow-up.

A 20-month-old boy presented with 1-year history of persistent fever, cough, and progressive abdominal distention. Abdominal ultrasonography showed hepatomegaly and multiple calcifications in the liver and spleen. Thoracic computed tomography showed multiple mediastinal lymph nodes and consolidation in both lungs. Additionally, there was a 2-cm thick retroperitoneal soft tissue mass destroying the T7-8 and L1-L2 vertebral bodies. The patient was preliminarily diagnosed with miliary tuberculosis (TB) and Pott's disease, and began administering anti-TB treatment consisting of isoniazid, rifampin, ethambutol, and pyrazinamide. Acid-resistant bacilli analysis and mycobacterial culture of the biopsy specimen of Pott's abscess were positive. Mycobacterial culture and PCR of gastric aspirate were also positive. The patient's condition progressively improved with anti-TB treatment and he received 12 months of antiTB therapy. At the end of the treatment all of the patient's symptoms were relieved and he was well except for kyphosis. Miliary TB complicated by Pott's abscess is a very rare presentation of childhood TB. The presented case shows that when Pott's abscess is diagnosed and surgically corrected without delay, patients can recover without squeal.