Immunogenicity, safety and clinical outcomes of the SARS-CoV-2 BNT162b2 vaccine in adolescents with type 1 diabetes

IntroductionThe mRNA-based BNT162b2 (Pfizer-BioNTech) vaccine has been shown to elicit robust systemic immune response and confer substantial protection against the severe coronavirus disease (COVID-19), with a favorable safety profile in adolescents. However, no data exist regarding immunogenicity, reactogenicity and clinical outcomes of COVID-19 vaccines in adolescents with type 1 diabetes (T1D). In this prospective observational cohort study, we examined the humoral immune responses and side effects induced by the BNT162b2 vaccine, as well as, the rate and symptomatology of laboratory-confirmed COVID-19 vaccine breakthrough infections after completion of dual-dose BNT162b2 vaccination in adolescents with T1D and compared their data with those of healthy control adolescents. The new data obtained after the vaccination of adolescents with T1D could guide their further COVID-19 vaccination schedule.MethodsA total of 132 adolescents with T1D and 71 controls were enrolled in the study, of whom 81 COVID-19 infection-naive adolescents with T1D (patient group) and 40 COVID-19 infection-naive controls (control group) were eligible for the final analysis. The response of participants to the BNT162b2 vaccine was assessed by measuring their serum IgG antibodies to the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 4–6 weeks after the receipt of first and second vaccine doses. Data about the adverse events of the vaccine was collected after the receipt of each vaccine dose. The rate of COVID-19 vaccine breakthrough infections was evaluated in the 6-month period following second vaccination.ResultsAfter vaccinations, adolescents with T1D and controls exhibited similar, highly robust increments in anti-SARS-CoV-2 IgG titers. All the participants in the patient and control groups developed anti-SARS-CoV-2 IgG titers over 1,050 AU/ml after the second vaccine dose which is associated with a neutralizing effect. None of the participants experienced severe adverse events. The rate of breakthrough infections in the patient group was similar to that in the control group. Clinical symptomatology was mild in all cases.ConclusionOur findings suggest that two-dose BNT162b2 vaccine administered to adolescents with T1D elicits robust humoral immune response, with a favorable safety profile and can provide protection against severe SARS-CoV-2 infection similar to that in healthy adolescents

Comparison of tangential and traditional methods for ultrasound guided percutaneous renal biopsy

Perkütan böbrek biyopsisi (PBB) renal parankim hastalıklarında uygulanan rutin bir metot olup klinisyene tanı, tedavi ve hastalığın prognozu hakkında önemli bilgiler sağlamaktadır. Radyologlar ve deneyimli nefrologlar tarafından ultrason eşliğinde yapılan PBB tanısal yeterlilik ve komplikasyonlar açısından etkin ve güvenilir bir yöntemdir. Biz bu çalışmamızda ultrason eşliğinde yapılan erişkin böbrek parankim biyopsilerinde tanjansiyel ve geleneksel yöntemleri doku yeterliliği ve komplikasyonlar açısından karşılaştırmayı amaçladık. Erişkin Nefroloji ve Romatoloji servislerinden böbrek parankim biyopsisi için kliniğimize yönlendirilen 69 hasta çalışmaya dâhil edildi. Randomize ve prospektif olarak tanjansiyel yöntem kullanılarak 34 hastaya (20 erkek, 14 kadın, ortalama yaş 48.9 ± 18.7, aralık 18–82 yaş), geleneksel yöntem kullanılarak 35 hastaya (19 erkek, 16 kadın, ortalama yaş 48 ± 17.6, aralık 18–74) PBB yapıldı. Biyopsiler en az 500 böbrek biyopsisi tecrübesi bulunan girişimsel radyolog tarafından otomatik biyopsi tabancası kullanılarak 18G iğne ile yapıldı. 66 hastaya nativ, üç hastaya transplant böbrek biyopsisi yapıldı. Nativ böbrek biyopsileri pron pozisyonda sol böbrek alt polünden, transplant biyopsiler yüzüstü pozisyonda mesaneye uzak kesimden yapıldı. Her hastadan iki kere doku alındı. Tanjansiyel yöntemde transvers düzlemde iğne traktusu böbrek alt pol korteksine olabildiğince paralel olacak şekilde, geleneksel yöntemde ise sagital düzlemde iğne traktusu böbrek alt pol korteksine dik olacak ve renal hilus korunacak şekilde biyopsiler alındı. En sık biyopsi endikasyonu Nefrotik Sendrom (%39.1) olup en sık görülen iki histopatolojik tanı FSGS (%30.4) ve MGN (%13) idi. Tanjansiyel yöntemde ortalama glomerül sayısı 19.06, geleneksel yöntemde ise 12.37 bulundu (p= 0.000). Ayrıca birim uzunluk başına glomerül sayısını karşılaştırdığımızda tanjansiyel yöntemde 0.85/mm, geleneksel yöntemde ise 0.58/mm olup, tanjansiyel yöntemde daha fazlaydı (p=0.001). Optimal (≥15 glomerül içeren) ve suboptimal (<15 glomerül içeren) materyal olarak iki yöntemi karşılaştırdığımızda tanjansiyel yöntemde optimal spesimen sayısını anlamlı olarak daha fazla bulduk (p=0.004). Yetersiz tanı gelen beş hastanın hepsine geleneksel yöntemle biyopsi yapılmıştı. İki (%2.9) hastada (biri tanjansiyel, diğeri geleneksel yöntem uygulanan) transfüzyon gerektirecek perirenal hematom oluştu (majör komplikasyon). Tanjansiyel yöntem uygulanan dört (%11.8) hastada, geleneksel yöntem uygulanan dokuz (%25.7) hastada minör komplikasyon (makroskopik hematüri ve tedavi gerektirmeyen perirenal hematom) gelişti. Risk faktörleri ve komplikasyon ilişkisini değerlendirdiğimizde komplikasyon gelişen grupta sistolik ve diyastolik kan basınçlarının daha yüksek, biyopsi öncesi hemoglobin değerlerinin ise daha düşük olduğunu saptadık (p<0.05). Yaş, cinsiyet, boy, kilo, beden kitle indeksi, kreatinin, üre, glomerüler filtrasyon hızı ile komplikasyonlar arasında ilişki saptanmadı. Ayrıca endikasyonlar ve histopatolojik tanıların da komplikasyonlar ile ilişkisi saptanmadı. Sonuç olarak tanjansiyel yöntem, geleneksel yöntemle karşılaştırıldığında daha yüksek tanısal yeterlilik oranına ve daha düşük komplikasyon oranına sahip olup perkütan böbrek biyopsilerinde güvenle kullanılabilir. İşlem öncesi hastaların kan basıncı değerlerinin 140/90 mmHg’nın altında ve Hb değerlerinin de 10 g/dl’nin üzerinde tutulmasının komplikasyonları azaltmada etkisi olacağını düşünmekteyiz.Percutaneous renal biopsy (PRB) is a method routinely applied in renal parenchymal diseases and provides important information for clinicians about diagnosis, treatment and prognosis of disease. PRB, which is performed by radiologists and experienced nephrologists is an effective and reliable method in terms of diagnostic efficiency and complications. In this research, we aimed to compare tangential and traditional methods in adult kidney parenchymal biopsies performed with ultrasound in terms of tissue adequacy and complications. Sixty-nine patients directed from adult nephrology and rheumatology services to our clinic for kidney parenchymal biopsy were included in this study. PRB was performed on 34 patients (20 men, 14 women, average age 48.9 ± 18.7, age range 18-82) by using tangential method as randomized and prospectively, and on 35 patients (19 men, 16 women, average age 48 ± 17.6, age range 18-74) by using traditional method. Biopsies were performed with 18G needle by interventional radiologist having experience of at least 500 kidney biopsies by using automatic biopsy gun. Native renal biopsy was performed on 66 patients and transplant renal biopsy on three patients. Native renal biopsies was performed from lower pole of left kidney on prone position, transplant biopsies from the parts away from bladder on facedown position. Tissues were taken from each patient twice. Biopsies were taken in a way that needle tractus was in parallel to lower pole cortex of kidney in transverse plane in tangential method; in a way that needle tractus was in vertical to lower pole cortex of kidney and protecting renal hilus in sagittal plane in traditional method. The most common indication for biopsy was Nephrotic Syndrome (39.1%); and the two most common histopathological diagnoses were FSGS (30.4%) and MNG (13%). In tangential method, average number of glomerulus was found as 19.06, and in traditional method as 12.37 (p=0.000). Besides, when we compared glomerulus number for per unit length, it was 0.85/mm in tangential method, 0.58/mm in traditional method, so it was more in tangential method (p=0.001). When we compared two methods as of optimal (including ≥15 glomeruli) and suboptimal (including ≥15 glomeruli) materials, we found that optimal specimen number was meaningfully higher in tangential method (p=0.004). By using traditional methods, biopsy was performed on five patients came with insufficient diagnosis. In two (2.9%) patients (one was applied to tangential, another one to traditional method), perirenal hematoma requiring transfusion was occurred (major complication). Minor complication (perirenal hematoma which does not require treatment and macroscopic hematuria) was occurred in four patients (11.8%) applied to tangential method and in nine patients (25.7%) applied to traditional method. When we evaluated the relation between risk factors and complication, we found that systolic and diastolic blood pressures were higher, pre-biopsy hemoglobin values were lower in group where the complication developed. The relation could not be determined between age, gender, height, weight, body mass index, creatinine, urea and glomerular filtration rate with the complications. In addition, the relation could not be determined between indications and histopathological diagnosis with the complications. As a result, when comparing tangential method with traditional method, it has higher diagnostic efficiency rate and lower complication rate and also it can be used in percutaneous renal biopsies safely. We consider that keeping blood pressure values of patients under 140/90 mmHg and their Hb values over 10 g/dl before the procedure will influence in reducing complications

The Effect of Using the Intermediate Dose Calculation Module on Volumetric Modulated Arc Technique Plan Quality in Esophagus Cancer

OBJECTIV

Array-comparative genomic hybridization results in clinically affected cases with apparently balanced chromosomal rearrangements

Carriers of apparently balanced chromosomal rearrangements (ABCRs) have a 2-3-fold higher risk of carrying an abnormal phenotype, when compared to the average population. Apparently balanced chromosomal rearrangements can be imbalanced at the submicroscopic level, and changes in the gene structure, formation of a new chimeric gene, gain or loss of function of the genes and altered imprinting pattern may also affect the phenotype. Chromosomal microarray (CMA) is an efficient tool to detect submicroscopic imbalances at the breakpoints as well as in the whole genome. We aimed to determine the effectiveness of array-comparative genomic hybridization (aCGH) application in phenotypically affected cases with ABCRs at a single center from Turkey. Thirty-four affected cases (13 prenatal, 21 postnatal) carrying ABCRs were investigated with CMA. In postnatal series, ABCRs were familial in 7 and de novo in 14 cases. Seven de novo cases were imbalanced (in postnatal series 33.3% and in de novo cases 50.0%). Out of 13 prenatal cases, five were familial and eight were de novo in origin and two de novo cases were imbalanced (in 15.4% prenatal series and in 25.0% de novo cases). No cryptic imbalance was observed in familial cases. The anomaly rates with array studies ranged between 14.3-25.0% in familial and between 20.0-57.5% in de novo cases of postnatal series in the literature. Studies focused on prenatal ABCR cases with abnormal ultrasound findings are limited and no submicroscopic imbalance was reported in the cohorts. When de novo postnatal or prenatal results were combined, the percentage of abnormalities detected by CMA was 40.9%. Taking this contribution into consideration, all ABCRs should be investigated by CMA even if the fetal ultrasound findings are normal

HOLOPROSENCEPHALY: CHROMOSOMAL ABNORMALITIES IN THE ETIOPATHOGENESIS OF 127 ANTENATAL CASES

Objective: Holoprosencephaly (HPE, #MIM 236100) is the most common developmental defect of midline cleavage in the human forebrain. Environmental, genetic, and multifactorial causes are involved in its etiology. About half of the cases have chromosome aberrations such as trisomies 13 and 18, triploidy and structural imbalances. Single gene mutations have been shown in ~25% of cases. In this retrospective study, we aimed to determine the etiological factors related to HPE in 127 fetuses. Material and Method: This study comprises 127 prenatally diagnosed fetal HPE samples from a period of 25 years, which were evaluated by karyotyping, fluorescence in situ hybridization (FISH) and aCGH investigation. Results: A total of 64 (50.39%) chromosome aberrations were identified in this cohort. The predominant chromosomal abnormality was trisomy 13 (n=38), which was followed by trisomy 18 (n=8) and triploidy (n=5). Terminal 7q deletion was the most frequent structural anomaly (n=10, of which 5 were de novo deletion, 4 were an unbalanced product of maternal translocations and one unknown in origin) and the deletion of 18p was detected in one case. In the remaining two cases, we detected trisomy 20 and pericentric inversion 11 coincidentally. Conclusion: This study, indicates that in the presence of clinical findings suggesting HPE, cytogenetic and molecular cytogenetic studies should be performed. An aCGH study must also be done for submicroscopic chromosomal anomalies, to determinetheir sizes, real breakpoints and identify possible novel genes that might play a role in HPE etiology