Diagnosing Cystic Fibrosis in the 21st Century-A Complex and Challenging Task.

Cystic fibrosis (CF) is a chronic and potentially life-threatening condition, wherein timely diagnosis assumes paramount significance for the prompt initiation of therapeutic interventions, thereby ameliorating pulmonary function, addressing nutritional deficits, averting complications, mitigating morbidity, and ultimately enhancing the quality of life and extending longevity. This review aims to amalgamate existing knowledge to provide a comprehensive appraisal of contemporary diagnostic modalities pertinent to CF in the 21st century. Deliberations encompass discrete delineations of each diagnostic modality and the elucidation of potential diagnostic quandaries encountered in select instances, as well as the delineation of genotype-phenotype correlations germane to genetic counseling endeavors. The synthesis underscores that, notwithstanding the availability and strides in diagnostic methodologies, including genetic assays, the sweat test (ST) retains its position as the preeminent diagnostic standard for CF, serving as a robust surrogate for CFTR functionality. Prospective clinical investigations in the realm of CF should be orchestrated with the objective of discerning novel diagnostic modalities endowed with heightened specificity and sensitivity.

Diagnosis, Management, and Prognosis of Cystic Fibrosis-Related Liver Disease in Children.

Cystic fibrosis (CF) is a multifaceted disorder predominantly investigated for its pulmonary manifestations, yet patients with CF also exhibit a spectrum of extrapulmonary manifestations, notably those involving the hepatobiliary system. The latter constitutes the third leading cause of morbidity and mortality in individuals with CF. Cystic fibrosis-related liver disease (CFLD), with an escalating prevalence, manifests diverse clinical presentations ranging from hepatomegaly to cirrhosis and hepatopulmonary syndrome. Consequently, early detection and appropriate management are imperative for sustaining the health and influencing the quality of life of CF patients afflicted with CFLD. This review aims to consolidate existing knowledge by providing a comprehensive overview of hepatobiliary manifestations associated with CF. It delineates the clinical hepatobiliary manifestations, diagnostic methodologies, incorporating minimally invasive markers, and therapeutic approaches, encompassing the impact of novel CFTR modulators on CFLD. Given the exigency of early diagnosis and the intricate management of CFLD, a multidisciplinary team approach is essential to optimize care and enhance the quality of life for this subset of patients. In conclusion, recognizing CF as more than solely a pulmonary ailment, the authors underscore the imperative for further clinical investigations to establish a more robust evidence base for CFLD management within the continuum of this chronic disease.

Diagnosis and Management of Gastrointestinal Manifestations in Children with Cystic Fibrosis.

Cystic fibrosis (CF) is primarily known for its pulmonary consequences, which are extensively explored in the existing literature. However, it is noteworthy that individuals with CF commonly display gastrointestinal (G-I) manifestations due to the substantial presence of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in the intestinal tract. Recognized as pivotal nonpulmonary aspects of CF, G-I manifestations exhibit a diverse spectrum. Identifying and effectively managing these manifestations are crucial for sustaining health and influencing the overall quality of life for CF patients. This review aims to synthesize existing knowledge, providing a comprehensive overview of the G-I manifestations associated with CF. Each specific G-I manifestation, along with the diagnostic methodologies and therapeutic approaches, is delineated, encompassing the impact of innovative treatments targeting the fundamental effects of CF on the G-I tract. The findings underscore the imperative for prompt diagnosis and meticulous management of G-I manifestations, necessitating a multidisciplinary team approach for optimal care and enhancement of the quality of life for affected individuals. In conclusion, the authors emphasize the urgency for further clinical studies to establish a more robust evidence base for managing G-I symptoms within the context of this chronic disease. Such endeavors are deemed essential for advancing understanding and refining the clinical care of CF patients with G-I manifestations.

An Update in Cystic Fibrosis-Related Diabetes in Children and Adolescents.

This paper delineates several aspects of cystic fibrosis-related diabetes (CFRD)-a common complication of cystic fibrosis (CF). CFRD exhibits a predilection for older individuals with CF, yet it also extends its influence on children and adolescents. Scientific insights postulate a potential link between CFRD and the aberrant mucus production within the pancreas, thereby culminating in pancreatic insufficiency. This, in turn, perturbs the synthesis of insulin, a pivotal endocrine hormone responsible for the regulation of glycemic levels. Standardized protocols advocate for the systematic screening of CFRD among all individuals with CF, commencing at the age of 10 years using the oral glucose tolerance test (OGTT). Therapeutic modalities encompass insulin therapy, dietary adjustments, and the vigilant monitoring of glycemic parameters. The overarching objective is to maintain blood glucose levels within a targeted range to mitigate the advent of diabetic complications. Untreated or sub-optimally managed CFRD can precipitate a spectrum of deleterious health ramifications, encompassing cardiovascular afflictions, neuropathy, renal dysfunction, and ocular complications.

Factors Associated with Increased Risk of Urosepsis during Pregnancy and Treatment Outcomes, in a Urology Clinic.

Background and Objectives: Urosepsis is a significant cause of maternal and fetal mortality. While certain risk factors for urinary tract infections (UTIs) in pregnant women are well established, those associated with an elevated risk of urosepsis in pregnant women with upper UTIs remain less defined. This study aims to identify factors linked to an increased risk of urosepsis and examine urologic treatment outcomes in such cases. Materials and Methods: We conducted a retrospective analysis on 66 pregnant women diagnosed with urosepsis over a nine-year period. A control group included 164 pregnant women with upper UTIs, excluding urosepsis, admitted during the same timeframe. This study highlights factors potentially contributing to urosepsis risk, including comorbidities like anemia, pregnancy-related hydronephrosis or secondary to reno-ureteral lithiasis, prior UTIs, coexisting urological conditions, and urologic procedures. Outcomes of urologic treatments, hospitalization duration, obstetric transfers due to fetal distress, and complications associated with double-J catheters were analyzed. Results: Pregnant women with urosepsis exhibited a higher prevalence of anemia (69.7% vs. 50.0%, p = 0.006), 2nd-3rd grade hydronephrosis (81.8% vs. 52.8%, p = 0.001), and fever over 38 °C (89.4% vs. 42.1%, p = 0.001). They also had a more intense inflammatory syndrome (leukocyte count 18,191 ± 6414 vs. 14,350 ± 3860/mmc, p = 0.001, and C-reactive protein (CRP) 142.70 ± 83.50 vs. 72.76 ± 66.37 mg/dL, p = 0.001) and higher creatinine levels (0.77 ± 0.81 vs. 0.59 ± 0.22, p = 0.017). On multivariate analysis, factors associated with increased risk for urosepsis were anemia (Odds Ratio (OR) 2.622, 95% CI 1.220-5.634), 2nd-3rd grade hydronephrosis (OR 6.581, 95% CI 2.802-15.460), and fever over 38 °C (OR 11.612, 95% CI 4.804-28.07). Regarding outcomes, the urosepsis group had a higher rate of urological maneuvers (87.9% vs. 36%, p = 0.001), a higher rate of obstetric transfers due to fetal distress (22.7% vs. 1.2%, p = 0.001), and migration of double-J catheters (6.1% vs. 0.6%, p = 0.016), but no maternal fatality was encountered. However, they experienced the same rate of total complications related to double-J catheters (19.69% vs. 12.80%, p > 0.05). The pregnant women in both groups had the infection more frequently on the right kidney, were in the second trimester and were nulliparous. Conclusions: Pregnant women at increased risk for urosepsis include those with anemia, hydronephrosis due to gestational, or reno-ureteral lithiasis, and fever over 38 °C. While the prognosis for pregnant women with urosepsis is generally favorable, urological intervention may not prevent a higher incidence of fetal distress and the need for obstetric transfers compared to pregnant women with uncomplicated upper UTIs.

Mutations of filament-aggregating protein gene in Romanian children diagnosed with atopic dermatitis.

Association of atopic dermatitis (AD) and several mutations of various genes of the immune system, in particular filament-aggregating protein gene (FLG) has been investigated in many studies. The association between defective FLG and AD in the Romanian population has not been assessed or published. The present study focused on the genetic background of AD, aiming to assess the prevalence of FLG mutations in Romanian patients with AD. Genetic background of AD was tested for common FLG-mutations: R501X, 2282del4, S3247X and R2447X. The study involved 48 Romanian Caucasian children aged between two months and six years diagnosed with AD, and 48 healthy volunteers; DNA extraction involved 50% of the patients to give samples by using buccal swabs and 50% by collection of whole blood samples. Genetic predisposition was evaluated based on family history, atopy history and profilaggrin genotyping. DNA extracted from blood samples was adequate to study FLG mutations, although no mutation was identified. Genetic factors do not have a unique critical role in AD; therefore, environmental factors unquestionably play an important role in this disease, but the clear-cut part that these factors trigger toward increasing the risk of AD in childhood is still obscure.

Different evolution in the treatment of a severe persistent asthma in 2 twins: Case report and review of the literature.

RATIONALE: Asthma is a multifactorial disease with complex genetic inheritance. In children under the age of 5 years, the diagnosis of asthma is a challenge. PATIENT CONCERN: We present the case of twin sisters under the same treatment for persistent asthma, but with different evolution over the time. DIAGNOSES: One of the sister is diagnosed with severe persistent bronchial asthma associated with bronchiectasis and dyslipidemia and the other one only with mild persistent asthma. INTERVENTIONS: At each admission the treatment for the exacerbations and the underlying respiratory infections was represented by antibiotics, short-acting ß2 agonists, and, sometimes, oxygen and systemic corticosteroids. As chronic treatment, they received in the last period inhaled corticosteroids associated with long-acting ß2 agonist. OUTCOMES: Until the age of 6.5 years, they had similar diagnoses and treatment; from this point one was asymptomatic, with normal pulmonary function tests. The other one had a more complicated evolution which led to a severe crisis by the age of 10 years old. LESSONS: Although asthma is a multifactorial disease with complex genetic inheritance, the genetics has its limits. Our twins had a similar onset with the same genetic inheritance, with the same risk factors, with the same comorbidities and with the same treatment. In this context, different evolutions of severe persistent asthma require more extensive genetic investigations. PATIENT CONCERN: We present the case of twin sisters under the same treatment for persistent asthma, but with different evolution over the time.

First Report of Pachyonychia Congenita Type PC-K6a in the Romanian Population.

Pachyonychia congenita (PC) is a rare autosomal dominant skin disorder, with unknown prevalence, although it is estimated there are between 2,000 and 10,000 cases of PC worldwide. The International PC Research Registry (IPCRR) has currently identified (as of November 2016) 746 individuals (in 403 families) with genetically confirmed PC. Heterozygous mutations, predominantly missense mutations, in any one of five keratin genes, KRT6A, KRT6B, KRT6C, KRT16, or KRT17 cause PC. The predominant clinical findings include plantar keratoderma, plantar pain and variable dystrophy of some or all toenails and/ or fingernails. Oral leukokeratosis, follicular hyperkeratosis, cysts of various types and natal teeth may also be present. We report the first case of genetically confirmed PC from Romania due to a mutation in KRT6A, p.Arg466Pro.

Intertrigo Caused by Streptococcus pyogenes.

Well-demarcated, beefy-red lesions of the skin folds, without satellite lesions, are the clinical hallmarks of intertrigo, frequently misdiagnosed especially in young children. We present 6 cases of streptococcal intertrigo to draw attention to this easily diagnosed and treated, but frequently overlooked, infection.

Particularities of the management and the treatment in a rare sepsis with Candida tropicalis of a Collodion baby: Case report.

RATIONALE: Collodion baby is a rare autosomal recessive disorder. It can be the first expression of some forms of ichthyosis. PATIENT CONCERNS: The authors present the case of a newborn diagnosed with severe Collodion baby syndrome who required prolonged hospitalization in the intensive care unit because of infectious complications like the fungal sepsis and other bacterial superinfections. DIAGNOSES: The case has many diagnostic and therapeutic particularities and management difficulties. Skin culture, dermatological and genetic exam were required. INTERVENTIONS: The treatment required multidisciplinary involvement: neonatologist, pediatrician, geneticist, dermatologist, psychologist, ophthalmologist, audiologist. OUTCOMES: The evolution during hospitalization was slowly favorable, but later, after a few months, it developed some complications. LESSONS: In our case, skin injuries, total parenteral nutrition, aggressive and prolonged antibiotic therapy, intravenous devices, high hospitalization duration were risk factors for colonization and sepsis with fungi, especially in the neonatal period, sometimes with severe evolution and prognosis.

Indications and limitations of histopathological skin investigation of Henoch-Schönlein purpura in children.

UNLABELLED: Henoch-Schönlein purpura, the most common primary vasculitis of the child, may cause, in some cases with atypical clinical picture, diagnostic difficulties with a significant prognosis impact, especially when occasionally "silent" renal symptoms coexist. The purpose of our study is, on one hand, to determine the histopathological investigation needs of Henoch-Schönlein purpura in children with atypical cutaneous manifestations or incomplete forms of illness and, on the other hand, to point out the correlation between the cutaneous histopathological aspects and other clinical and biological manifestations. RESULTS: Optical microscopy revealed signs of leukocytoclastic vasculitis in 11 of the 22 cases with ulcerative necrotic purpura and atypical clinical picture. Immunohistochemical examination proved that these were associated with IgA deposits on the vascular wall, sometimes accompanied by C3, fibrin, IgM and CD3. The severity of the skin manifestations was directly correlated with the severity of digestive and/or renal symptoms. CONCLUSIONS: Skin biopsy is indicated only in the atypical or incomplete forms of disease to support positive diagnosis by immunohistochemical evidence of the vascular IgA deposits. The severity and persistence of the ulceronecrotic purpuric rash seems to be directly related rather to the severity of the other clinical manifestations (digestive or renal) than to the generalized extensively purpuric appearance.

[Liver involvement in celiac disease in children]. / Afectarea hepatica în boala celiaca la copil.

UNLABELLED: Celiac disease (CD) is an autoimmune systemic enteropathy triggered by gluten intake in patients with genetic susceptibility, characterized by clinic polymorphism: classic forms, mainly with digestive features, and atypical forms, liver involvement being a part of them. In present, any unknown cytolysis requires screening serologic determinations for CD. AIMS: to assess the presence of liver manifestations in children diagnosed with CD, the outcome of liver function with gluten-free diet (GFD) and also to emphasize the importance of the immunological screening for CD in patients with unknown etiology liver dysfunctions. MATERIAL AND METHODS: The trial was formed by 120 patients diagnosed with CD between January 2007 - December 2010 in 2nd and 3rd Pediatric Clinics of "Sf. Maria" Hospital Iasi; liver function was assessed; viral hepatitis and autoimmune hepatitis markers were determined; all patients were given GFD, hepatoprotective agents and antivirals specific to each form of hepatitis; the transaminases level variation was followed in time. RESULTS: 12 of the CD diagnosed patients (10, 14%) had altered liver function at the onset of disease; the only abnormality was the increased transaminases level in 57, 14% of cases; HBsAg was found positive in 33, 33% (4 cases); liver biopsy in one patient evidenced steatosis. The study has shown that 4% of the patients with cryptogenetic hepatitis have a silent form of CD, the serologic screening for AGA, AEA, ATGA being essential for diagnosis. CONCLUSIONS: we have to rule out CD in patients with liver disease of unknown etiology, before we consider it as "cryptogenetic"; occurrence of cytolysis in the absence of positive viral markers requires the assessment of screening tests for CD.

[Osteopenia in children with juvenile idiopathic arthritis]. / Osteopenia la copiii cu artrita juvenila idiopatica.

UNLABELLED: The aim of the study was to evaluate the presence and etiopathogenesis of osteopenia in 41 children with Juvenile Idiopathic Arthritis (JIA). METHODS: Bone status was evaluated by quantitative ultrasound using a Sunlight Omnisense 7000s Ultrasound Bone Sonometer. Measurements were performed at the distal radius and midshaft tibia. Results were obtained as Speed of sound (SOS) and Z-score. We used standardised clinical evaluation (modified Giannini's criteria, CHAQ). ESR, Fibrinogen, serum calcium, magnesium, alkaline phosphatase, protein electrophoresis, 25-OH vitamin D (RIA) and urinary Hydroxyproline were obtained in all patients. Osteopenia was present in 15 (36.5%) patients. Statistical analysis was performed with SPSS 13.0. RESULTS: Age, sex, age at onset, disease duration, life standards and duration of corticotherapy and methotrexate treatment were not related to osteopenia in our study. The disease activity, evaluated by clinical criteria, ESR and Fibrinogen, was strongly associated with osteopenia (p<0.001). Nutritional status was an independent risk factor for osteopenia (p<0.001). Low serum calcium (p=0.034), magnesium (p=0.010), 25-OH vitamin D (p=0.091) and alkaline phosphatase (p=0.31) were more frequent in patients with osteopenia. Hydroxyproline was increased in all patients with osteopenia (p<0.001). CONCLUSIONS: Osteopenia was a frequent (36.5%) complication of JIA in our study. The disease activity and nutritional status were the most important risk factors for osteopenia. The increase of bone reabsorption was the main pathogenic mechanism of osteopenia in our study. Calcium and magnesium deficits were related to osteopenia. Decrease of bone synthesis was not associated with osteopenia in the present study.

[Clinical and epidemiologic considerations in the role of newborn diseases causing asthma in children]. / Consideratii clinico-epidemiologice privind implicarea patologiei neonatale în inducerea astmului bronsic la copil.

The authors present results of a multidisciplinary study in 712 children with asthma concerning the role of certain newborns events and the role of feeding in the onset of disease: resuscitation during the delivery--82.68%, respiratory distress--75.5%, Apgar score = 7 - 58.56%, bottle-feeding 50.50%, multi-pregnancy--44.23%, abnormal pregnancy--20.11%, premature infant and small for gestational age infant 10.60%, mother age less then 20 years 8.6%.

[The effects of inhaled corticoids on bone density in asthmatic children]. / Efectele corticoterapiei inhalatorii asupra densitatii osoase la copiii cu astm bronsic.

OBJECTIVE: To evaluate bone status of asthmatic children on chronic inhaled corticoid therapy. METHODS: Bone densitometry was performed by Quantitative ultrasound (QUS) of the distal radius in 74 asthmatic children, evaluating Z-score; serum levels of 25 hydroxyvitamin D were measured in 10 cases. RESULTS: 28 of 74 children had osteopenia, defined as Z scores lower than -1. Statistic analyzes showed a significant correlation (p <0.05) of osteopenia with the duration of inhaled corticoid therapy (CSI), the absence of correlation with the dose of CSI, age, sex, severity step and duration of the disease. 25 hydroxyvitamin D was low in 8 of the 10 cases with osteopenia. Osteopenia was present in 7 children who were not under CSI, but have received multiple trials of oral corticoids for severe exacerbations. CONCLUSIONS: Osteopenia was present in 52% of children that were under inhaled corticoids for more than 12 months and it correlated with the duration of CSI, but not with the daily dose. Systemic corticoid use is a significant cause of osteopenia in asthmatic children.

[Pathogenic basis of treatment in children with bronchial asthma and gastroesophageal reflux]. / Bazele patogenetice ale tratamentului astmului bronsic asociat cu reflux gastro-esofagian la copil.

The relationship between bronchial asthma (BA) and gastro-esophageal reflux (GER) impose to study by frequency, reciprocally prognosis and therapeutics difficulty. Coexistence of both diseases is suggested by presence of asthmatics symptoms in non-atopic patients, difficult control and resistance of the specific treatment of asthma disease, worsening of respiratory symptoms in circumstances which favored GER. Pathogenetic relationship between BA and GER in children is the result of the associations- digestive particularity and: esophago-bronchial neurogenic mechanism produced by micro-aspiration , genetic or obtained inflammations development by commune Th2 mediators, medications effects. Classical treatments (H2-inhibitors, prokinetics agents, inhibitors of protonic pumps) is associated of the antiasthmatics "controller" therapy and in the future, anti-cytokine and anti-receptor therapy.

[Therapeutic strategy in children with Henoch-Schönlein purpura]. / Strategii terapeutice în purpura henoch-schonlein la copil.

Henoch-Schönlein Purpura (HSP) is the most frequent childhood primary immune vasculitis which affected skin, joints, gastro-intestinal tract and kidney. Renal involvement signs the future disease prognosis. The HSP don't have etiologic treatment but its immuno-histological aspects, leukocytoclastic vasculitis with immune complexes, imposed the including in the therapeutic equation, immunosuppressive and/or cytotoxic drugs, plasmapheresis, kidney transplant (severe renal deficiency resistant to medical treatment) and surgical treatment (in severe gastro-intestinal complications). Identifications of serum and/or urinary markers for the therapeutic answer contribute to appreciate long prognosis disease and precocious and individualized treatment.

[Systemic lupus erythematosus in children. I: clinical and age dependent evolutive characteristics]. / Lupusul eritematos sistemic (LES) la copil. Nota I: Particularitati clinice si evolutive dependente de vârsta.

The individualized, retrospective study of 14 children with SLE (4-16 years) pointed out a series of clinical and age dependent evolutive characteristics. Below the age of 10 years old (lot 1:2 boys and 4 girls), SLE started as a prolonged fever syndrome (5-16 weeks) in the majority of cases; for 2 children the severe poliarthritis resistant to the AINS therapy is associated with the durable absence of the antinuclear seric antibody (ANA). For the same age group a high frequency of neurological manifestations (5/6 cases) was noticed. After the age of 10 years old (lot II: 8 girls) the symptoms incidence at debut is close to the one of the adult, the cutanat and renal manifestations in evolution were dominant (7/8 cases). The 7 months absence of ANA characterises a case that started with hepatomegaly, severe neurological and physiological manifestations and microscopic hematuria. The follow-up lasted until the age of 16 years old; the patients were clinically tested for severe renal complication. The correct application of the classical criteria of diagnostic (ARA, 1982), and in the last few years the application of the ponderat score (Mayer, 1998), allows us to establish an early diagnostic and a rapid evaluation of a relapse, therefore influencing the treatment.