DIAPH1-Deficiency is Associated with Major T, NK and ILC Defects in Humans.

Loss of function mutations in Diaphanous related formin 1 (DIAPH1) are associated with seizures, cortical blindness, and microcephaly syndrome (SCBMS) and are recently linked to combined immunodeficiency. However, the extent of defects in T and innate lymphoid cells (ILCs) remain unexplored. Herein, we characterized the primary T, natural killer (NK) and helper ILCs of six patients carrying two novel loss of function mutation in DIAPH1 and Jurkat cells after DIAPH1 knockdown. Mutations were identified by whole exome sequencing. T-cell immunophenotyping, proliferation, migration, cytokine signaling, survival, and NK cell cytotoxicity were studied via flow cytometry-based assays, confocal microscopy, and real-time qPCR. CD4+ T cell proteome was analyzed by mass spectrometry. p.R351* and p.R322*variants led to a significant reduction in the DIAPH1 mRNA and protein levels. DIAPH1-deficient T cells showed proliferation, activation, as well as TCR-mediated signaling defects. DIAPH1-deficient PBMCs also displayed impaired transwell migration, defective STAT5 phosphorylation in response to IL-2, IL-7 and IL-15. In vitro generation/expansion of Treg cells from naïve T cells was significantly reduced. shRNA-mediated silencing of DIAPH1 in Jurkat cells reduced DIAPH1 protein level and inhibited T cell proliferation and IL-2/STAT5 axis. Additionally, NK cells from patients had diminished cytotoxic activity, function and IL-2/STAT5 axis. Lastly, DIAPH1-deficient patients' peripheral blood contained dramatically reduced numbers of all helper ILC subsets. DIAPH1 deficiency results in major functional defects in T, NK cells and helper ILCs underlining the critical role of formin DIAPH1 in the biology of those cell subsets.

Recurrent symptomatic urolithiasis in a patient with cystic fibrosis.

A 6-month-old girl, previously diagnosed with cystic fibrosis (CF), was admitted to hospital for nephrolithiasis. Her parents were first-degree cousins. The patient underwent endoscopic stone management. Despite no family history of stones and medical treatment with potassium citrate, the patient developed recurrent renal stones and atypical urinary tract infections during follow-up. Basic investigations were all normal. Due to consanguinity and early presentation of nephrolithiasis, metabolic causes such as cystinuria and hyperoxaluria were considered. Cystinuria was excluded due to normal cystine levels. High urinary oxalate excretion was found as expected due to absorptive (secondary) hyperoxaluria in CF patients. An early stone burden in the patient with a history of medical treatment and consanguinity led us to perform a genetic testing. Genetic testing revealed a missense homozygous variant in exon 1 of the AGXT gene. The patient was diagnosed with primary hyperoxaluria type 1. Two rare life-threatening genetic diseases were found together in the same child.

Comparison of refugee patients with cystic fibrosis and their counterpart children from Turkey during the war.

Since the outbreak of the Syrian civil war in 2011, the population of Arab refugees in Turkey has rapidly increased. While cystic fibrosis (CF) is believed to be rare among Arabs, recent studies suggest it is underdiagnosed. This study aims to present the demographic, clinical, and genetic characteristics of CF patients among Arab refugees in Turkey. Additionally, a comparison is made between the findings in the National CF Registry 2021 in Turkey (NCFRT) and the refugee CF patient group. The study included refugee patients between the ages of 0 and 18 years who were diagnosed with CF and received ongoing care at pediatric pulmonology centers from March 2011 to March 2021. The study examined demographic information, age at diagnosis, age of diagnosis of patients through CF newborn screening (NBS), presenting symptoms, CF transmembrane conductance regulator (CFTR) mutation test results, sputum culture results, weight, height, and body mass index (BMI) z score. Their results were compared with the NCFRT results. The study included 14 pediatric pulmonology centers and 87 patients, consisting of 46 (52.9%) boys and 41 (47.1%) girls. All of the patients were Arab refugees, with 80 (92%) being Syrian. All the patients were diagnosed in Turkey. The median age at diagnosis of patients was 22.33 (interquartile range, 1-258) months. The median age of diagnosis of patients through NBS was 4.2 (interquartile range, 1-12) months. The median age of older patients, who were unable to be included in the NBS program, was 32.3 (interquartile range, 3-258) months. Parental consanguinity was observed in 52 (59.7%) patients. The mutation that was most frequently found was F508del, which accounted for 22.2% of the cases. It was present in 20 patients, constituting 32 out of the total 144 alleles. There was a large number of genetic variations. CFTR genotyping could not be conducted for 12 patients. These patients had high sweat tests, and their genetic mutations could not be determined due to a lack of data. Compared to NCFRT, refugee patients were diagnosed later, and long-term follow-up of refugee CF patients had significantly worse nutritional status and pseudomonas colonization.  Conclusion: Although refugee CF patients have equal access to NBS programs and CF medications as well as Turkish patients, the median age at diagnosis of patients, the median age of diagnosis of patients through NBS, their nutritional status, and Pseudomonas colonization were significantly worse than Turkish patients, which may be related to the difficulties of living in another country and poor living conditions. The high genetic heterogeneity and rare mutations detected in the refugee patient group compared to Turkish patients. Well-programmed NBS programs, thorough genetic studies, and the enhancement of living conditions for refugee patients in the countries they relocate to can have several advantages such as early detection and improved prognosis. What is Known: • Children who have chronic diseases are the group that is most affected by wars. • The outcome gets better with early diagnosis and treatment in patients with Cystic Fibrosis (CF). What is New: • Through the implementation of a newborn screening program, which has never been done in Syria previously, refugee patients, the majority of whom are Syrians were diagnosed with cystic fibrosis within a duration of 4 months. • Despite equal access to the newborn screening program and CF medications for both Turkish patients and refugee patients, the challenges of living in a foreign country have an impact on refugees.

Childhood interstitial lung disease in Turkey: first data from the national registry.

The childhood interstitial lung diseases (chILD) Turkey registry (chILD-TR) was established in November 2021 to increase awareness of disease, and in collaboration with the centers to improve the diagnostic and treatment standards. Here, the first results of the chILD registry system were presented. In this prospective cohort study, data were collected using a data-entry software system. The demographic characteristics, clinical, laboratory, radiologic findings, diagnoses, and treatment characteristics of the patients were evaluated. Clinical characteristics were compared between two main chILD groups ((A) diffuse parenchymal lung diseases (DPLD) disorders manifesting primarily in infancy [group1] and (B) DPLD disorders occurring at all ages [group 2]). There were 416 patients registered from 19 centers. Forty-six patients were excluded due to missing information. The median age of diagnosis of the patients was 6.05 (1.3-11.6) years. Across the study population (n = 370), 81 (21.8%) were in group 1, and 289 (78.1%) were in group 2. The median weight z-score was significantly lower in group 1 (- 2.0 [- 3.36 to - 0.81]) than in group 2 (- 0.80 [- 1.7 to 0.20]) (p < 0.001). When we compared the groups according to chest CT findings, ground-glass opacities were significantly more common in group 1, and nodular opacities, bronchiectasis, mosaic perfusion, and mediastinal lymphadenopathy were significantly more common in group 2. Out of the overall study population, 67.8% were undergoing some form of treatment. The use of oral steroids was significantly higher in group 2 than in group 1 (40.6% vs. 23.3%, respectively; p = 0.040).   Conclusion: This study showed that national registry allowed to obtain information about the frequency, types, and treatment methods of chILD in Turkey and helped to see the difficulties in the diagnosis and management of these patients. What is Known: • Childhood interstitial lung diseases comprise many diverse entities which are challenging to diagnose and manage. What is New: • This study showed that national registry allowed to obtain information about the frequency, types and treatment methods of chILD in Turkey and helped to see the difficulties in the diagnosis and management of these patients. Also, our findings reveal that nutrition should be considered in all patients with chILD, especially in A-DPLD disorders manifesting primarily in infancy.

The 2D and 3D MR arthrographic description of aponeurotic expansion of supraspinatus tendon and biceps tendon anomaly in a large patient cohort.

OBJECTIVE: To describe the aponeurotic expansion of supraspinatus tendon (AEST) and biceps tendon abnormalities with magnetic resonance (MR) arthrographic examinations and determine their prevalence in patients, we performed a high-resolution 3D direct MR arthrography. MATERIALS AND METHODS: This was a retrospective study of 700 shoulder MR arthrograms performed between May 2010 and January 2022. Extension in the coronal plane of an AEST on 3D fat-suppressed T1-weighted volumetric interpolated breath-hold examination (VIBE) MR arthrography was identified. Based on its morphology, the AEST on MR arthrography was divided into four subtypes: absence of tendinous thickness in the bicipital synovial surface or intra-synovial tendon-like structure in the bicipital groove, thin and flat tendinous thickness ≥1 mm of bicipital synovium, oval tendinous structure less than half the size of the adjacent biceps tendon, oval tendinous structure more than half the size of the adjacent biceps tendon, and oval tendinous structure larger than the adjacent biceps tendon. Based on its origin and termination, aponeurotic expansions can be divided into three subtypes: proximal pulley zone, middle humeral neck zone, and distal myotendinous junction zone. Association with the biceps synovium of the AEST was categorized into three types: intra-synovial, extra-synovial, and trans-synovial. RESULTS: An AEST in the anterior shoulder joint in 3D VIBE MR arthrography images was identified in 63 (9%) of 700 arthrograms. The most common arthrographic type of AEST was type 1-this was detected in 39 of 63 patients. The most common course type of the AEST was anteriorly midline. The most common distal insertion type was at the tenosynovial sheath of the long head of the biceps tendon (LHBT) in the middle humeral neck zone-this was detected in 31 of 63 patients. There were only 10 MR arthrograms biceps tendon abnormality, including 4 biceps agenesis and 6 split ruptures. CONCLUSION: A 2D and high-resolution 3D MR arthrography can demonstrate the anatomical detail around the bicipital groove and facilitate the differentiation between a biceps tendon anomaly and an AEST. On high-resolution 3D MR arthrographic images, the AEST tends to be in the anterior midline and anteromedial portions of the biceps synovium with intra-synovial, extra-synovial, and trans-synovial courses and its three different insertion types.

Effect of Pre-exercise Sodium Citrate Ingestion on Repeated Sprint Performance in Soccer Players.

ABSTRACT: Kuru, D, Aktitiz, S, Atakan, MM, Köse, MG, Turnagöl, HH, and Kosar, SN. Effect of pre-exercise sodium citrate ingestion on repeated sprint performance in soccer players. J Strength Cond Res 38(3): 556-562, 2024-This study aimed to test the hypothesis that sodium citrate (CIT) administered 180 minutes before exercise improves repeated sprint performance in athletes within a field-based setting. Twenty male soccer players (mean ± SD : age = 20.9 ± 2.3 years; body mass [BM] = 73.8 ± 5.9 kg) performed a running-based anaerobic sprint test (RAST) with 0.5 g·kg -1 BM of CIT or with placebo (PLC; NaCl) ingestion 180 minutes before exercise in a randomized, crossover, and double-blind design, with at least 6 days between the trials. Blood samples were collected before exercise and at first, third, fifth, and seventh minutes after exercise to analyze blood pH, bicarbonate, and lactate levels. Gastrointestinal symptoms were also monitored at 30-minute intervals for 180 minutes after CIT and PLC ingestion. Pre-exercise blood pH (CIT = 7.49 ± 0.03 vs. PLC = 7.41 ± 0.02) and bicarbonate (CIT = 30.57 ± 1.33 vs. PLC = 25.25 ± 1.52) increased with CIT compared with PLC ( p < 0.001). Blood pH, bicarbonate, and lactate at the first, third, fifth, and seventh minutes after RAST with CIT were higher than PLC ( p < 0.05), except for lactate at first minute ( p > 0.05). Compared with PLC, CIT ingestion significantly improved minimum power output ( p = 0.024) and percentage decrement score ( p = 0.023). Gastrointestinal symptoms were significantly higher after CIT ingestion vs. PLC at 30th ( p = 0.003) and 60th minutes ( p = 0.010). However, there were no significant differences at 90th, 120th, 150th, or 180th minutes ( p > 0.05). The ingestion of 0.5 g·kg -1 BM of CIT 180 minutes before exercise is an effective ergogenic aid for improving repeated sprint ability as evidenced by improvements in minimum power output and percentage decrement score.

Elderly and aged asthma have different characteristics: results of a multicenter study.

Background/aim: Characteristics of asthma in the elderly population is not well-known. The aim of the present study was to evaluate asthma in the elderly population, to compare disease characteristics between patients diagnosed <60 (aged asthma) and ≥60 (elderly asthma) years of age. Materials and methods: The study was a prospective, multicenter, cross-sectional type. A questionnaire was filled out to patients 60 years of age and over, that have been followed for asthma for at least 3 months. Asthma Control Test (ACT), eight-item Morisky Medication Adherence Scale (MMAS-8) was filled out, inhaler device technique was assessed. Results: A total of 399 patients were included from 17 tertiary care centers across the country. Mean age was 67.11 years and 331 (83%) were female. The age at asthma diagnosis was ≥60 in 146 (36.6%) patients. Patients diagnosed ≥60 years were older (p < 0.001), had higher education level (p < 0.001), more commonly had first-degree relative with asthma (p = 0.038), asthma related comorbidities (p = 0.009) and accompanying rhinitis/rhinosinusitis (p = 0.005), had better asthma control (p = 0.001), were using less controller medications (p = 0.014). Inhaler technique was correct in 37% of the patients with no difference in between the groups. Treatment compliance was better in elderly asthma patients (p < 0.001). In the multivariate logistic regression analysis, having well-controlled asthma (odds ratio = 1.61, CI = 1.04-2.51), and high medication adherence rate (odds ratio = 2.43, CI = 1.48-4.0) were associated with being in the elderly asthma group. Conclusion: The characteristics of asthma are different among patients aged 60 years and over which seems to be related to onset age of asthma. In our cohort, the elderly asthma patients had higher education level, and treatment adherence and asthma control was better. Patients diagnosed ≥60 years of age did not have more severe disease.

Detection of the glenoid bare spot by non-arthrographic MR imaging, conventional MR arthrography, and 3D high-resolution T1-weighted VIBE MR arthrography: comparison with CT arthrography.

OBJECTIVES: To determine the diagnostic accuracy of non-arthrographic MR imaging, conventional MR arthrography, and 3D T1-weighted volumetric interpolated breath-hold examination (VIBE) MR arthrography sequences as compared with a CT arthrography in the diagnosis of glenoid bare spot. METHODS: A retrospective study of 216 patients who underwent non-arthrographic MR imaging, conventional MR arthrography, VIBE MRI arthrography, and CT arthrogram between January 2011 and March 2022 was conducted. The diagnostic accuracy of non-arthrographic MR imaging, direct MR arthrography, and VIBE MRI arthrography in the detection of glenoid bare spot was compared with that of CT arthrography. All studies were reviewed by 2 MSK radiologists. Interobserver agreement for MR imaging and MR arthrographic findings was calculated. RESULTS: Sixteen of 216 patients were excluded. Twenty-three of 200 shoulders had glenoid bare spot on CT arthrographic images. The glenoid bare spot was detected in 11 (47.8%) and 7 (30.4%) patients on conventional non-arthrographic MR images and in 18 (78.3%) and 16 (69.6%) patients on conventional MR arthrograms by observers 1 and 2, respectively. Both observers separately described the bare spot in 22 of 23 patients (95.7%) on 3D volumetric MR arthrograms. Interobserver variabilities were fair agreement for conventional non-arthrographic MR imaging (κ = 0.35, p < 0.05), moderate agreement for conventional MR arthrogram (κ = 0.50, p < 0.05), and near-perfect agreement for 3D volumetric MR arthrogram reading (κ = 0.87, p < 0.05). CONCLUSIONS: A 3D high-resolution T1-weighted VIBE MR arthrography sequence may yield diagnostic performance that is comparable with that of CT arthrography in the diagnosis of glenoid bare spot. KEY POINTS: •Glenoid bare spot should not be misdiagnosed as a transchondral defect of the glenoid surface by radiologists. •A 3D high-resolution T1-weighted VIBE MR arthrography sequence may be used as a high-sensitivity imaging technique in the diagnosis of glenoid bare spot.

Evaluation of specificity and sensitivity of IRT/IRT protocol in the cystic fibrosis newborn screening program: 6-year experience of three tertiary centers.

We aimed to evaluate cutoff values of immunoreactive trypsinogen (IRT)/IRT and determine relationship between IRT values and clinical characteristics of children with cystic fibrosis (CF). This study is cross-sectional study. Data of children with positive newborn screening (NBS) between 2015 and 2021 were evaluated in three pediatric pulmonology centers. Age at admission, sex, gestational age, presence of history of meconium ileus, parental consanguinity, sibling with CF, and doll-like face appearance, first and second IRT values, sweat chloride test, fecal elastase, fecal fat, biochemistry results, and age at CF diagnosis were recorded. Sensitivity and specificity of IRT cutoff values were evaluated. Of 815 children with positive NBS, 58 (7.1%) children were diagnosed with CF. Median values of first and second IRT were 157.2 (103.7-247.6) and 113.0 (84.0-201.5) µg/L. IRT values used in current protocol, sensitivity was determined as 96.6%, specificity as 17.2% for first IRT, and 96.6% sensitivity, 20.5% specificity for second IRT. Positive predictive value (PPV) was determined as 7.1%. When cutoff value for first IRT was estimated as 116.7 µg/L, sensitivity was 69.0% and specificity was 69.6%, and when cutoff value was set to 88.7 µg/L for second IRT, sensitivity was 69.0% and specificity was 69.0%. Area under curve was 0.757 for first and 0.763 for second IRT (p < 0.001, p < 0.001, respectively). PPV was calculated as 4.3%.    Conclusion: Although sensitivity of CF NBS is high in our country, its PPV is significantly lower than expected from CF NBS programs. False-positive NBS results could have been overcome by revising NBS strategy. What is Known: • Although immunoreactive trypsinogen elevation is a sensitive test used in cystic fibrosis newborn screening, its specificity is low. • In countries although different algorithms are used, all strategies begin with the measurement of immunoreactive trypsinogen in dried blood spots. What is New: • In our study, it was shown that use of the IRT/IRT protocol for cystic fibrosis newborn screening is not sufficient for the cut-off values determined by the high number of patients. • Newborn screening strategy should be reviewed to reduce false positive newborn screening results.

The associations between the clinical course of children with tracheostomy and their mothers' depression, burnout, burden, and self-esteem.

AIMS AND OBJECTIVES: The aim of this study was to evaluate the clinical features of children with tracheostomy and the predictors of psychological status of their primary caregivers in order to determine the associations between the children's clinical course with their caregivers' psychological status. BACKGROUND: The caregivers of children with tracheostomy are responsible for providing basic tracheostomy care at home. All these responsibilities may be associated with significant changes in family members' lifestyles, daily routines and family dynamics. DESIGN: This study is a cross sectional study. METHODS: Data of the family's socioeconomic status and clinical status of children with tracheostomy were noted in four paediatric pulmonology centers. The Beck Depression Inventory, Maslach Burnout Inventory, Zarit Caregiver Burden Scale, and Rosenberg Self-esteem Scale were used for psychological measurements of the caregivers. The STROBE checklist was used for this study. RESULTS: Eighty-five children and their primary caregivers were enrolled in the study. The children's median age was 4.1 years. Thirty-eight of them were dependent on home ventilators. Twenty-one had bacterial colonisation. All children's primary caregivers were their mothers. Beck Depression Inventory scores of mothers of children with colonisation were higher. Number of hospitalizations in previous 6 months was related to mothers' emotional exhaustion and depersonalization scores. Duration of children's hospitalizations in previous 6 months was positively correlated to mothers' emotional exhaustion, depersonalization, and Beck Depression Inventory scores. CONCLUSIONS: Mothers of children with tracheostomy may experience psychological conditions, such as high levels of depression, burnout, burden and low levels of self-esteem. Frequent and long-term hospitalizations of children correlated with mother's depression and burnout. Therefore, primary caregivers should be evaluated and supported psychologically. RELEVANCE TO CLINICAL PRACTICE: Preventing mothers of children with tracheostomy from experiencing psychological conditions such as depression, burnout, burden and low self-esteem can also increase the quality of care for children.

Caspase-1 and interleukin-18 in children with post infectious bronchiolitis obliterans: a case-control study.

The exact immunological mechanisms of post infectious bronchiolitis obliterans (PIBO) in childhood are not fully known. It has been shown that the inflammasome and IL-18 pathway play important roles in the pathogenesis of lung fibrosis. We aimed to investigate the role of caspase-1, IL-18, and IL-18 components in PIBO. From January to May 2020, children with PIBO, children with history of influenza infection without PIBO, and healthy children were asked to participate in the study in three pediatric pulmonology centers. Serum caspase-1, IL-18, IL-18BP, IL-18R, and INF-γ levels were measured by ELISA and compared between the 3 groups. There were 21 children in the PIBO group, 16 children in the influenza group, and 39 children in the healthy control group. No differences in terms of age and gender between the 3 groups were found. IL-18 and IL-18BP levels were higher in the healthy control group (p = 0.018, p = 0.005, respectively). IL-18R was higher in the PIBO group (p = 0.001) and caspase-1 was higher in the PIBO and influenza group than the healthy control group (p = 0.002). IFN-γ levels did not differ between the 3 groups. IL-18BP/IL-18 was higher in the influenza group than the PIBO group and the healthy control group (p = 0.003). CONCLUSIONS: Caspase-1 level was increased in patients with PIBO which suggests that inflammasome activation may have a role in fibrosis; however, IL-18 level was found to be low. Mediators other than IL-18 may be involved in the inflammatory pathway in PIBO. Further immunological studies investigating inflammasome pathway are needed for PIBO with chronic inflammation. WHAT IS KNOWN: • Post infectious bronchiolitis obliterans (PIBO) is a rare, severe chronic lung disease during childhood which is associated with inflammation and fibrosis which lead to partial or complete luminal obstruction especially in small airways. • The exact immunological mechanisms of PIBO in childhood are not fully known. WHAT IS NEW: • Inflammasome activation persists even years after acute infection and may play a role in fibrosis in PIBO. • Mediators other than IL-18 may be involved in these inflammatory pathway.

Cell-Specific Expression Pattern of Toll-Like Receptors and Their Roles in Animal Reproduction.

Toll-like receptors (TLRs), a part of the innate immune system, have critical roles in protection against infections and involve in basic pathology and physiology. Secreted molecules from the body or pathogens could be a ligand for induction of the TLR system. There are many immune and non-immune types of cells that express at a least single TLR on their surface or cytoplasm. Those cells may be a player in a defense system or in the physiological regulation mechanisms. Reproductive tract and organs contain different types of cells that have essential functions such as hormone production, providing an environment for embryo/fetus, germ cell production, etc. Although lower parts of reproductive organs are in a relationship with outsider contaminants (bacteria, viruses, etc.), upper parts should be sterile to provide a healthy pregnancy and germ cell production. In those areas, TLRs bear controller or regulator roles. In this chapter, we will provide current information about physiological functions of TLR in the cells of the reproductive organs and tract, and especially about their roles in follicle selection, maturation, follicular atresia, ovulation, corpus luteum (CL) formation and regression, establishment and maintenance of pregnancy, sperm production, maturation, capacitation as well as the relationship between TLR polymorphism and reproduction in domestic animals. We will also discuss pathogen-associated molecular patterns (PAMPs)-induced TLRs that involve in reproductive inflammation/pathology.

Circulating fibrocyte level in children with cystic fibrosis.

BACKGROUND: This study aimed to evaluate circulating fibrocyte levels in cystic fibrosis (CF) patients during stable and exacerbation periods of the condition. METHODS: The study group consisted of 39 patients diagnosed with CF and 20 healthy controls. Individuals included in the study were divided into three groups: CF, CF exacerbated, and a healthy control group. Their circulating fibrocyte levels were compared. Findings from a pulmonary function test and high-resolution computed tomography of the lung were evaluated and compared. RESULTS: The circulating fibrocyte count was found to be significantly higher in patients with CF compared with the exacerbated and control groups. No correlation was found between the forced expiratory volume in 1 s and forced vital capacity values in the pulmonary function test and the circulating fibrocyte count. The circulating fibrocyte count in patients (in the CF group) with positive findings in the high-resolution computed tomography was statistically significantly lower. CONCLUSIONS: The circulating fibrocyte level in the peripheral blood of the patients with CF was increased.

Clinical findings of patients with cystic fibrosis according to newborn screening results.

BACKGROUND: Cystic fibrosis (CF) is a lethal recessive genetic disease caused by loss of function associated with mutations in the CF trans-membrane conductance regulator. It is highly prevalent (approximately 1 in 3,500) in Caucasians. The aim of this study was to compare demographic and clinical features, diagnostic tests, treatments, and complications of patients with CF whose newborn screening (NBS) with twice-repeated immune reactive trypsinogen testing was positive, normal, and not performed. METHODS: In this study, 359 of all 1,488 CF patients recorded in the CF Registry of Turkey in 2018, who had been born through the process of NBS, were evaluated. Demographic and clinical features were compared in patients diagnosed with positive NBS (Group 1), normal (Group 2), or without NBS (Group 3). RESULTS: In Group 1, there were 299 patients, in Group 2, there were 40 patients, and in Group 3, there were 20 patients. Among all patients, the median age at diagnosis was 0.17 years. The median age at diagnosis was higher in Groups 2 and 3 than in Group 1 (P = 0.001). Fecal elastase results were higher in Group 2 (P = 0.033). The weight z-score was lower and chronic Staphylococcus aureus infection was more common in Group 3 (P = 0.017, P = 0.004, respectively). CONCLUSIONS: Frequency of growth retardation and chronic S. aureus infection can be reduced with an early diagnosis using NBS. In the presence of clinical suspicion in patients with normal NBS, further analyses such as genetic testing should be performed, especially to prevent missing patients with severe mutations.

Whole and segmental body composition changes during mid-follicular and mid-luteal phases of the menstrual cycle in recreationally active young women.

BACKGROUND: Changes in oestradiol and progesterone hormones and associated fluid retention during the menstrual cycle phases might affect body composition (BC) in women. AIM: The main objectives of this study were to determine the changes in whole and segmental BC by dual-energy x-ray absorptiometry (DXA) and bioelectrical impedance (BIA) during the mid-follicular (MFP) and mid-luteal (MLP) phases. SUBJECTS AND METHODS: Thirty recreationally active young women participated in this study. BC was measured by DXA and BIA during MFP and MLP. A mixed linear model for repeated measures analysis was used to determine the differences between the two phases. RESULTS: Body mass was higher during MLP than MFP, while total body water, total and segmental fat mass and fat percentages measured by both BIA and DXA were similar during the two phases. DXA-derived fat-free mass and soft lean mass in the android region were higher during MLP than MFP. Large variability in individual responses was evident. CONCLUSION: On average, whole and segmental BC variables do not change significantly between MFP and MLP. However, given the large variability among the individual responses, it is suggested to perform repeated BC measurements during the same phase of the menstrual cycle.

Type 1 Plasminogen Deficiency With Pulmonary Involvement: Novel Treatment and Novel Mutation.

Type 1 plasminogen deficiency is a rare genetic disorder. Type 1 plasminogen deficiency is characterized by fibrin-rich pseudomembrane formation on mucosal surfaces, particularly the conjunctiva. Tracheobronchial tree involvement is a less common reported manifestation of type 1 plasminogen deficiency. Pseudomembranes in the tracheobronchial tree may result in respiratory compromise and ultimately fail if not recognized and treated. Currently, there is no specific replacement therapy approved for the treatment of congenital plasminogen deficiency. In the present paper, we report that type 1 plasminogen deficiency with novel frameshift mutation and pulmonary involvement was treated initially with systemic fresh frozen plasma followed by pulmonary lavage with fresh frozen plasma and tissue plasminogen activator.

Blood hyperreosinophilia: A diagnostic challenge.

A very detailed differential diagnosis is necessary to investigate the causes of blood hypereosinophilia. In the differential diagnosis of hypereosinophilia with pulmonary involvement, primary and secondary eosinophilic lung diseases should be kept in mind, and more specific diagnoses should be considered in those with a history of nasal polyposis and asthma. Here, it was aimed to present a case of organ-limited hypereosinophilia with asthma and nasal polyposis.

Antiinflammatory effects of adalimumab, tocilizumab, and steroid on lipopolysaccharide-induced lung injury.

BACKGROUND: Acute lung injury (ALI) is a major cause of death in the intensive care unit. Lipopolysaccharide (LPS) induced lung injury is the most widely used experimental ALI model and provides opportunities for new targeting therapy. In this study, we investigated the effects of tocilizumab, adalimumab, and methylprednisolone in LPS-induced acute lung injury. METHODS: Lung injury was established by intratracheal instillation of LPS. The rats were randomly divided into six groups: LPS, control, and treatment groups (adalimumab, tocilizumab, methylprednisolone, adalimumab + tocilizumab). Bronchoalveolar lavage (BAL) and lung tissues were collected at 48 h and 96 h following LPS administration from each group. For histological analysis, hematoxylin-eosin (H&E) staining was performed. The sections were obtained for immunohistochemical analysis. IL-6 and TNF-alpha immunoreactivity were measured. RESULTS: Intratracheal LPS application resulted in inflammatory cell infiltration of interstitial and alveolar spaces and thickening of the alveolar wall. All treatment groups showed significantly amelioration compared to LPS at 48 h. Interestingly, adalimumab and adalimumab + tocilizumab groups showed a significant amelioration of the lung histoarchitecture, compared to the prednisolone group at 96 h (p = 0.028, p = 0.025, respectively). Compared to the control group, LPS stimulation resulted in a significant increase in IL-6 and TNF-alpha immunoreactivity (p < 0.001). IL-6 and TNF-alpha expression were markedly reduced in all treatment groups at 48 h but the reduction was greater in the adalimumab and tocilizumab group than in the steroid. Administration with adalimumab and/or tocilizumab effectively decreased expression of TNF-alpha (p = 0.001) and IL-6 (p < 0.001) at 96 h, but prednisolone did not exert an effective decrease (p > 0.05). DISCUSSION: Adalimumab and/or tocilizumab significantly reduce the release of proinflammatory cytokines and improve the tissue inflammation in the experimental model of ALI. Our results suggest that adalimumab and/or tocilizumab have a more potent antiinflammatory effect on lung injury than the steroid.

Combination of sentinel lymph node mapping and uterine frozen section examination to reduce side-specific lymphadenectomy rate in endometrial cancer: a Turkish Gynecologic Oncology Group study (TRSGO-SLN-002).

OBJECTIVE: This study aimed to find out whether side-specific pelvic lymphadenectomy can be omitted without compromising diagnostic efficacy according to "reflex frozen section" analysis of the uterus in case of sentinel lymph node (SLN) mapping failure. METHODS: Patients who underwent surgery for endometrial cancer with an SLN algorithm were stratified as low-risk or high-risk according to the uterine features on the final pathology reports. Two models for low-risk patients were defined to omit side-specific pelvic lymphadenectomy: strategy A included patients with endometrioid histology, grade 1-2, and <50% myometrial invasion irrespective of the tumor diameter; strategy B included all factors of strategy A with the addition of tumor diameter ≤2 cm. Theoretical side-specific pelvic lymphadenectomy rates were calculated for the two strategies, assuming side-specific pelvic lymphadenectomy was omitted if low-risk features were present on reflex uterine frozen examination, and compared with the standard National Comprehensive Cancer Network (NCCN) SLN algorithm. RESULTS: 372 endometrial cancer patients were analyzed. 230 patients (61.8%) had endometrioid grade 1 or 2 tumors with <50% myometrial invasion (strategy A), and in 123 (53.4%) of these patients the tumor diameter was ≤2 cm (strategy B); 8 (3.5%) of the 230 cases had lymphatic metastasis. None of them were detected by side-specific pelvic lymphadenectomy and metastases were limited to SLNs in 7 patients. At least one pelvic side was not mapped in 107 (28.8%) cases in the entire cohort, and all of these cases would require a side-specific pelvic lymphadenectomy based on the NCCN SLN algorithm. This rate could have been significantly decreased to 11.8% and 19.4% by applying reflex frozen section examination of the uterus using strategy A and strategy B, respectively. CONCLUSION: Reflex frozen section examination of the uterus can be a feasible option to decide whether side-specific pelvic lymphadenectomy is necessary for all the patients who failed to map with an SLN algorithm. If low-risk factors are found on frozen section examination, side-specific pelvic lymphadenectomy can be omitted without compromising diagnostic efficacy for lymphatic spread.

Passive Smoking and Disease Severity in Childhood Pneumonia Under 5 Years of Age.

OBJECTIVE: To objectively investigate the effect of passive smoking on pneumonia and disease severity in children aged less than 5 years by using cotinine as an indicator of passive smoking. METHODS: Between December 2015 and April 2016, children aged less than 5 years with pneumonia and age-matched healthy controls were included in this study, which was conducted at three tertiary pediatric pulmonology centers. A questionnaire was given to the parents regarding demographic data and smoking status at home. Urinary cotinine/creatinine ratio (CCR) was measured. The data from the pneumonia and control groups, as well as children with mild and severe pneumonia within the pneumonia group, were compared. RESULTS: A total of 227 subjects were included in the study; there were 74 children in the pneumonia group and 153 in the control group. The mean age of all the children was 33.4 ± 1.28 months. Of all subjects, 140 were male and 102 were exposed to passive smoking by their parents at home. There were statistically significant differences in age, number of people in the home, and mother's and father's age between the control and pneumonia groups (p < 0.05). No difference was found in the CCR in the control and pneumonia group (p > 0.05). Age and urinary CCR were significantly different between children with mild and severe pneumonia (p < 0.05). CONCLUSION: We showed that passive smoking exposure was associated with the development of severe pneumonia in children. Further studies are needed to examine the underlying cause in detail.