Coombs test positivity in cord blood: early detection of risky newborns and the assessment of their follow-up results

Objective Direct Coombs test (DCT) is a screening process to detect antibodies which are produced against the antigens in the red blood cells of newborns and cause hemolytic disease. In our study, we aimed to compare the demographic data and early period outcomes of the newborns with and without DCT positivity. Methods The data of all newborns who were born in our hospital between January 2019 and September 2019, of whose mothers gave informed consent before the labor and whose cord blood samples were examined were reviewed retrospectively. The data were analyzed by using SPPS 25 (IBM Corp. Released 2017; IBM SPSS Statistics for Windows, Version 25.0; IBM Corp., Armonk, NY, USA) statistics software. Results A total of 302 newborns were included in the study. The results of Direct Coombs test were positive in 27 cases. The phototherapy rate of the cases with positive DCT results was 74% (20/27). It was found that the cases with positive DCT results underwent more phototherapy, started to undergo phototherapy earlier, were hospitalized longer and had lower serum total bilirubin levels compared to the cases with negative DCT results, and these differences were statistically significant (p=0.003, p=0.015, p=0.038 and p=0.026, respectively). Conclusion Today, there is no specific method to prevent jaundice particularly for the newborns with a risk factor. The only thing to do for newborns at this point is to detect if they have risk factors or not, and to follow up newborns with risk factors appropriately. Direct Coombs test has still been playing an important role to predict hemolytic anemia and potential manifestation of hyperbilirubinemia in association with hemolytic anemia in the newborns, and to initiate treatment process as soon as possible

The frequency of Duchenne muscular dystrophy/Becker muscular dystrophy and Pompe disease in children with isolated transaminase elevation: results from the observational VICTORIA study

IntroductionElevated transaminases and/or creatine phosphokinase can indicate underlying muscle disease. Therefore, this study aims to determine the frequency of Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) in male children and Pompe disease (PD) in male and female children with isolated hypertransaminasemia.MethodsThis multi-center, prospective study enrolled patients aged 3–216 months with serum alanine transaminase (ALT) and/or aspartate transaminase (AST) levels >2× the upper limit of normal (ULN) for ≥3 months. Patients with a known history of liver or muscle disease or physical examination findings suggestive of liver disease were excluded. Patients were screened for creatinine phosphokinase (CPK) levels, and molecular genetic tests for DMD/BMD in male patients and enzyme analysis for PD in male and female patients with elevated CPK levels were performed. Genetic analyses confirmed PD. Demographic, clinical, and laboratory characteristics of the patients were analyzed.ResultsOverall, 589 patients [66.8% male, mean age of 63.4 months (standard deviation: 60.5)] were included. In total, 251 patients (188 male and 63 female) had CPK levels above the ULN. Of the patients assessed, 47% (85/182) of male patients were diagnosed with DMD/BMD and 1% (3/228) of male and female patients were diagnosed with PD. The median ALT, AST, and CPK levels were statistically significantly higher, and the questioned neurological symptoms and previously unnoticed examination findings were more common in DMD/BMD patients than those without DMD/BMD or PD (p < 0.001).DiscussionQuestioning neurological symptoms, conducting a complete physical examination, and testing for CPK levels in patients with isolated hypertransaminasemia will prevent costly and time-consuming investigations for liver diseases and will lead to the diagnosis of occult neuromuscular diseases. Trial RegistrationClinicaltrials.gov NCT04120168

Sub-clinic atherosclerosis in patients with postprandial reactive hypoglycemia

Aim: Hypoglycemia is associated with excessive cardiovascular mortality because of the pro-inflammatory and pro-atherothrombotic pathway stimulation. Hypoglycemia is known to affect the development of sub-clinic atherosclerosis. This study aims to determine the development of sub-clinic atherosclerosis in patients with postprandial reactive hypoglycemia by investigating thickness of carotid intima media and epicardial fat, and high-sensitivity C-reactive protein values and their relationships with each other. Material and Methods: 51 patients in total were included in the project, including 28 patients (37.50±10.82 years) who had hypoglycemia symptoms and who had hypoglycemia during prolonged oral glucose tolerance test and 23 healthy adult volunteers (35.01±10.92 years) as a control group. Subjects underwent echocardiographic examination including EFT and IMT measurement using transthoracic echocardiography. Results: Postprandial Reactive Hypoglycemia group were marked with higher high-sensitivity C-reactive protein levels (1.67±0.67 vs. 1.20±0.52; p= 0.007), carotid intima media thickness (0.65±0.10 vs. 0.50±0.10; p<0.001) and epicardial fat thickness (0.57±0.07 vs. 0.48±0.08; p= 0.001) values as compared to the control group. Conclusion: Patients with postprandial reactive hypoglycemia had impaired epicardial fat thickness and increased thickness of carotid intima media, and carotid intima media thickness linked with significantly with high-sensitivity C-reactive protein. These observations support the importance of chronic inflammation mechanism for the development of sub-clinic atherosclerotic disease in postprandial reactive hypoglycemia

Üniversite ve Meslek Seçimini Etkileyen Etmenler

Meslek seçimi, genç bireylerin yaşamını pek çok açıdan etkileyecek en önemli kararlardan biridir. Bu kararın en doğru şekilde verilmesi, onların gelecek hayatındaki başarısına, yaşamdan alacağı doyuma, fiziksel ve ruhsal sağlığına kadar pek çok alan üzerinde etkili olmaktadır. Bireylerin kariyer seçiminde sadece meslek seçimi değil, aynı zamanda üniversite tercihi de önemli rol oynamaktadır. Zira üniversite tercih aşamasına gelen adayların, kariyer gelişimine farklı bir açıdan bakarak eğitim almak istedikleri üniversitenin pek çok özelliğine dikkat ettikleri görülmektedir. Öğrencilerin üniversite ve bölüm tercihlerinde öğrencinin özellikleri (sosyoekonomik düzey, yeterlilikler vb.) ve dış etkiler (aile, arkadaş, öğretmen, uzaklık, kampüs özellikleri ve tanıtım faaliyetleri vb.) önemli rol oynamaktadır. Türkiye’deki mevcut yapı incelendiğinde meslek kazanımının meslek liseleri ya da üniversite lisans eğitimi ile kazanıldığı görülmektedir. Bu nedenle adayların üniversite ve üniversitede okuyacağı bölümü seçmeleri bir anlamda gelecekte yapacakları mesleği belirlemeleri anlamına gelmektedir. Bu çalışma, bilindiği kadarıyla Türkiye’de “Üniversite ve Meslek Tercihi” konusunda yapılan en kapsamlı çalışmadır. Bu çalışmanın sonuçları, adayların üniversite ve meslek tercihinde hangi faktörlere dikkat etmeleri gerektiği, ebeveynlerin ve psikolojik danışmanların öğrencilere yol gösterirken nelere dikkat etmeleri gerektiği ve üniversite yönetimlerinin başarılı öğrencileri kazanmaları için ne gibi stratejiler geliştirebileceği konularında oldukça yararlı bilgiler verecektir. Hacettepe Üniversitesi üst yönetiminin olağanüstü destekleri ile yürüttüğümüz çalışmamızda başta Rektörümüz Sayın A. Murat Tuncer olmak üzere, emeği geçen tüm araştırmacı ve öğrenci asistanlarımıza, Ankara’daki çeşitli okulların yetkililerine ve anketlerimizi samimi bir şekilde dolduran tüm lise son sınıf öğrencilerimize şükranlarımı sunuyorum

Clozapine regulates microglia and is effective in chronic experimental autoimmune encephalomyelitis

$\bf Objective:$ Progressive multiple sclerosis is characterized by chronic inflammation with microglial activation, oxidative stress, accumulation of iron and continuous neurodegeneration with inadequate effectiveness of medications used so far. We now investigated effects of iron on microglia and used the previously identified neuroprotective antipsychotic clozapine $\textit {in vitro}$ and in chronic experimental autoimmune encephalomyelitis (EAE). $\bf Methods:$ Microglia were treated with iron and clozapine followed by analysis of cell death and response to oxidative stress, cytokine release and neuronal phagocytosis. Clozapine was investigated in chronic EAE regarding optimal dosing and therapeutic effectiveness in different treatment paradigms. Animals were scored clinically by blinded raters. Spinal cords were analyzed histologically for inflammation, demyelination, microglial activation and iron accumulation and for transcription changes of regulators of iron metabolism and inflammation. Effects on immune cells were analyzed using flow cytometry. $\bf Results:$ Iron impaired microglial function $\textit {in vitro}$ regarding phagocytosis and markers of inflammation; this was regulated by clozapine, reflected in reduced release of IL-6 and normalization of neuronal phagocytosis. In chronic EAE, clozapine dose-dependently attenuated clinical signs and still had an effect if applied in a therapeutic setting. Early mild sedative effects habituated over time. Histologically, demyelination was reduced by clozapine and positive effects on inflammation strongly correlated with reduced iron deposition. This was accompanied by reduced expression of DMT-1, an iron transport protein. $\bf Conclusions:$ Clozapine regulates microglial function and attenuates chronic EAE, even in a therapeutic treatment paradigm. This well-defined generic medication might therefore be considered as promising add-on therapeutic for further development in progressive MS

Immune response in ofatumumab treated multiple sclerosis patients after SARS-CoV-2 vaccination

$\bf Objective:$ The pandemic induced by SARS-CoV-2 has huge implications for patients with immunosuppression that is caused by disorders or specific treatments. Especially approaches targeting B cells $\it via$ anti-CD20 therapy are associated with impaired humoral immune response but sustained cellular immunity. Ofatumumab is a human anti-CD20 directed antibody applied in low dosages subcutaneously, recently licensed for Multiple Sclerosis (MS). Effects of early ofatumumab treatment on alterations of immune cell composition and immune response towards SARS-CoV-2 are incompletely understood. $\bf Methods:$ We here investigated immune cell alterations in early ofatumumab (Ofa) treated patients and effects on humoral (titer, neutralization capacity against wild type, Delta and Omicron) and cellular immune responses in Ofa treated MS patients following a third vaccination against SARS-CoV-2 compared to healthy controls. $\bf Results:$ We show that a mean treatment duration of three months in the Ofa group led to near complete B cell depletion in line with altered composition of certain $CD4^{+}$ T cell subpopulations such as enhanced frequencies of naive and a decrease of non-suppressive regulatory T cells (Tregs). Titer and neutralization capacity against SARS-CoV-2 variants was impaired while cellular immune response was sustained, characterized by a strong T helper 1 profile (Th1). $\bf Interpretation:$ In summary, low dosage ofatumumab treatment elicits sustained depletion of B cells in line with alterations of immune cells, mainly Tregs. This is associated with impaired humoral immune response towards SARS-CoV-2 vaccination but preserved, Th1 driven cellular immunity adding crucial information regarding early effects of low dosage anti-CD20 therapy on humoral and cellular immunity

COVID-19 Disease in Presenting to the Pediatric Emergency Department: A Multicenter Study of 8886 Cases.

Background: The aim was to evaluate the epidemiological, clinical, laboratory, and radiologic data of children with SARS-CoV-2 positivity by polymerase chain reaction (PCR) together with treatment strategies and clinical out-comes and to evaluate cases of multisystem inflammatory syndrome in children (MIS-C) in this population.Methods: This was a multicenter retrospective observational cohort study performed in the pediatric emergency departments of 19 tertiary hospitals. From March 11, 2020, to May 31, 2021, children who were diagnosed with confirmed nasopharyngeal/tracheal specimen SARS-CoV-2 PCR positivity or positivity for serum-specific anti-bodies against SARS-CoV-2 were included. Demographics, presence of chronic illness, symptoms, history of con-tact with SARS-CoV-2 PCR-positive individuals, laboratory and radiologic investigations, clinical severity, hospital admissions, and prognosis were recorded.Results: A total of 8886 cases were included. While 8799 (99.0%) cases resulted in a diagnosis of SARS-CoV-2 with PCR positivity, 87 (1.0%) patients were diagnosed with MIS-C. Among SARS-CoV-2 PCR-positive patients, 51.0% were male and 8.5% had chronic illnesses. The median age was 11.6 years (IQR: 5.0-15.4) and 737 (8.4%) patients were aged <1 year. Of the patients, 15.5% were asymptomatic. The most common symptoms were fever (48.5%) and cough (30.7%) for all age groups. There was a decrease in the rate of fever as age increased (p < 0.001); the most common age group for this symptom was <1 year with the rate of 69.6%. There was known contact with a SARS-CoV-2 PCR-positive individual in 67.3% of the cases, with household contacts in 71.3% of those cases. In terms of clinical severity, 83 (0.9%) patients were in the severe-critical group. There was hospital admission in 1269 (14.4%) cases, with 106 (1.2%) of those patients being admitted to the pediatric intensive care unit (PICU). Among patients with MIS-C, 60.9% were male and the median age was 6.4 years (IQR: 3.9-10.4). Twelve (13.7%) patients presented with shock. There was hospital admission in 89.7% of these cases, with 29.9% of the patients with MIS-C being admitted to the PICU.Conclusion: Most SARS-CoV-2 PCR-positive patients presented with a mild clinical course. Although rare, MIS-C emerges as a serious consequence with frequent PICU admission. Further understanding of the characteristics of COVID-19 disease could provide insights and guide the development of therapeutic strategies for target groups.(c) 2022 Elsevier Inc. All rights reserved