The effect of a single hemodialysis session on pulmonary functions in patients with end-stage renal disease

Objective: Changes in pulmonary functions have not been thoroughly investigated in patients undergoing hemodialysis (HD). The aim of this study was to determine the effect of a single HD session on pulmonary functions, measured by spirometry, in patients with end-stage renal disease (ESRD) undergoing chronic hemodialysis (CHD) treatment. Methods: Thirty patients with ESRD who were on CHD treatment for at least 12 months between January 2018 and January 2020 were enrolled. The pre-dialysis and post-dialysis spirometric measurements were recorded by a portable spirometry device. Results: The mean age and HD vintage of 30 patients (70% male, 20% diabetic, mean BMI: 26.0 +/- 4.7 (kg/m(2))) were 55.6 +/- 11.4 years and 117.6 +/- 66.3 months, respectively. Half of the patients (50%) were smokers (mean 11.5 +/- 13.59 packs/year). The spirometric measurements of most of the patients were abnormal (40% restrictive, 30% obstructive respiratory disorder, 30% normal). The FEV3(L), predicted FEV1(%), FEF25(L), and predicted FEF25(%) values were significantly increased after the HD session. A positive correlation between BMI and Delta FEV3 (L) values (r = 0.377, P =.04) was observed. A significant improvement in FEV3 values after a single HD session was recorded, which was independently related to higher BMI (beta = 0.501, P <.01) and non-smoking (beta = 0.495, P <.05). Conclusion: Spirometric measurements are abnormal in most CHD patients, and a considerable improvement in pulmonary functions is possible with a single HD session. Having a high BMI and being a non-smoker appear to have significant positive effects on amelioration in FEV3 (L). Larger trials are needed to evaluate pulmonary functions in CHD patients

Inherited Bone Marrow Failure Syndromes in Children

Inherited bone marrow failure syndromes are disorders of hematopoiesis that are mostly encountered in childhood. Taking the basis from genetics, they are characterized by pancytopenia, increased risk of developing myelodysplastic syndrome and malignancy. Extrahematopoietic presentations are observed often in addition to symptoms related to defective hematopoiesis (also known as bone marrow failure). The biology, clinical features, and management of the main syndromes such as Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, congenital amegakaryocytic thrombocytopenia, Diamond-Blackfan anemia, and severe congenital neutropenia are briefly summarized in this review

Proteome analysis of human neutrophil granulocytes from patients with monogenic disease using data-independent acquisition

Neutrophil granulocytes are critical mediators of innate immunity and tissue regeneration. Rare diseases of neutrophil granulocytes may affect their differentiation and/or functions. However, there are very few validated diagnostic tests assessing the functions of neutrophil granulocytes in these diseases. Here, we set out to probe omics analysis as a novel diagnostic platform for patients with defective differentiation and function of neutrophil granulocytes. We analyzed highly purified neutrophil granulocytes from 68 healthy individuals and 16 patients with rare monogenic diseases. Cells were isolated from fresh venous blood (purity >99%) and used to create a spectral library covering almost 8000 proteins using strong cation exchange fractionation. Patient neutrophil samples were then analyzed by data-independent acquisition proteomics, quantifying 4154 proteins in each sample. Neutrophils with mutations in the neutrophil elastase gene ELANE showed large proteome changes that suggest these mutations may affect maturation of neutrophil granulocytes and initiate misfolded protein response and cellular stress mechanisms. In contrast, only few proteins changed in patients with leukocyte adhesion deficiency (LAD) and chronic granulomatous disease (CGD). Strikingly, neutrophil transcriptome analysis showed no correlation with its proteome. In case of two patients with undetermined genetic causes, proteome analysis guided the targeted genetic diagnostics and uncovered the underlying genomic mutations. Data-independent acquisition proteomics may help to define novel pathomechanisms in neutrophil diseases and provide a clinically useful diagnostic dimension

Genomic surveillance during the first two years of the COVID-19 pandemic – country experience and lessons learned from Türkiye

BackgroundTürkiye confirmed its first case of SARS-CoV-2 on March 11, 2020, coinciding with the declaration of the global COVID-19 pandemic. Subsequently, Türkiye swiftly increased testing capacity and implemented genomic sequencing in 2020. This paper describes Türkiye’s journey of establishing genomic surveillance as a middle-income country with limited prior sequencing capacity and analyses sequencing data from the first two years of the pandemic. We highlight the achievements and challenges experienced and distill globally relevant lessons.MethodsWe tracked the evolution of the COVID-19 pandemic in Türkiye from December 2020 to February 2022 through a timeline and analysed epidemiological, vaccination, and testing data. To investigate the phylodynamic and phylogeographic aspects of SARS-CoV-2, we used Nextstrain to analyze 31,629 high-quality genomes sampled from seven regions nationwide.ResultsTürkiye’s epidemiological curve, mirroring global trends, featured four distinct waves, each coinciding with the emergence and spread of variants of concern (VOCs). Utilizing locally manufactured kits to expand testing capacity and introducing variant-specific quantitative reverse transcription polymerase chain reaction (RT-qPCR) tests developed in partnership with a private company was a strategic advantage in Türkiye, given the scarcity and fragmented global supply chain early in the pandemic. Türkiye contributed more than 86,000 genomic sequences to global databases by February 2022, ensuring that Turkish data was reflected globally. The synergy of variant-specific RT-qPCR kits and genomic sequencing enabled cost-effective monitoring of VOCs. However, data analysis was constrained by a weak sequencing sampling strategy and fragmented data management systems, limiting the application of sequencing data to guide the public health response. Phylodynamic analysis indicated that Türkiye’s geographical position as an international travel hub influenced both national and global transmission of each VOC despite travel restrictions.ConclusionThis paper provides valuable insights into the testing and genomic surveillance systems adopted by Türkiye during the COVID-19 pandemic, proposing important lessons for countries developing national systems. The findings underscore the need for robust testing and sampling strategies, streamlined sample referral, and integrated data management with metadata linkage and data quality crucial for impactful epidemiological analysis. We recommend developing national genomic surveillance strategies to guide sustainable and integrated expansion of capacities built for COVID-19 and to optimize the effective utilization of sequencing data for public health action

The importance of cystatin-C for predicting nephrotoxicity in children with acute leukemia?s and non-Hodgkin lymphomas

Kliniğimizde tanı alan ve tedavi gören akut lenfoblastik lösemi, akut miyeloidlösemi ve Hodgkin-dışı lenfoma hastalarında böbrek fonksiyonları tedavileri süresincenefrotoksisite sıklığını ve nefrotoksistenin erken dönemde sistatin-C artışı ile belirlenmesininmümkün olup olmayacağının araştırılması amaçlandı.Gereç ve Yöntem: Bu çalışmaya Şubat 2006 - Mart 2007 tarihleri arasında SelçukÜniversitesi Pediatrik Hematoloji ve Pediatrik Onkoloji Bilim Dallarında tanı alan ve tedaviedilen 13 akut lenfoblastik lösemi, 8 akut myeloid lösemi ve 6 Hodgkin dışı lenfoma olmaküzere 27 (20 erkek, 7 kız) hastanın; hücum tedavisi başlangıcında, pekiştirme başlangıcındave idame tedavisi başlangıcında boy, serum üre, kreatinin, kreatinin klerens ve sistatin-Cdeğerleri kaydedildi.Bulgular: Tedavinin ilerleyen dönemlerindeki serum üre, sistatin-C ve kreatininklerens değerlerinde istatistiksel olarak anlamlı değişiklik saptanmazken serum kreatinindeğerinde; idame öncesinde pekiştirme öncesine göre anlamlı azalma mevcuttu.Sonuç: Akut lenfoblastik, myeloid lösemi, Hodgkin dışı lenfoma tedavisindekullanılan çoklu kanser ilaçları ile ciddi böbrek bozukluğu görülmedi. Sistatin-C glomerülerfiltrasyon hızını göstermede yüksek duyarlılık ve özgüllük değerlerine sahiptir. Bundan dolayıözellikle idrar toplamasında sorun olan çocuk hastalarda glomerüler filtrasyon hızının iyi birgöstergesi olabilir. Kanserli hastalarda serum sistatin-C düzeyine etki edebilecek diğerfaktörler için ileri araştırmalara ihtiyaç vardır.The importance of cystatin-C for predicting nephrotoxicity in children with acuteleukemia?s and non-Hodgkin lymphomasABSTRACTObjective: The aim of this study was to determine the incidence of nephrotoxicity inpatients with acute lymphoblastic, myeloid leukemia and non-Hodgkin lymphoma and toevaluate the effectiveness of serum cystatin-C for an early prediction of impairment of renalfunction.Material and Methods: Twenty-seven (20 boy, 7 girl; 13 children with acutelymphoblastic leukemia, 8 children with acute myeloid leukemia, 6 children with non-Hodgkin lymphoma) were enrolled in the study from February 2006 to March 2007. Serumurea, creatinine, creatinine clearance and cystatin-C concentrations and the heights of thepatients were determined before the introduction, consolidation and maintenance therapies.Results: The values of urea, cystatin-C, and creatinine clearance did not differstatistically by duration of the treatment. The values of serum creatinine before consolidationwere significantly lower than the values before maintenance.Conclusions: Multi-agent treatment for acute lymphoblastic, myeloid leukemia andnon-Hodgkin lymphoma is not associated with severe impairment of renal functions.Cystatin-C has high values of sensitivity and specificity to predict the glomeruler filtrationrate. Therefore it can be useful for determination of glomeruler filtration rate in children withcancer; especially who have difficulties in collecting 24-hours urine sample. Further studiesare needed to elucidate the effect of non-renal factors on cystatin-C.5