Diagnostic yield of microarrays in individuals with non-syndromic developmental delay and intellectual disability.

BACKGROUND: Intellectual disability (ID), or developmental delay (DD) when the individual is yet under 5 years of age, is evident before 18 years of age and is characterised by significant limitations in both intellectual functioning and adaptive behaviour. ID/DD may be clinically classified as syndromic or non-syndromic. Genomic copy number variations (CNVs) constitute a well-established aetiological subgroup of ID/DD. Overall diagnostic yield of microarrays is estimated at 10-25% for ID/DD, especially higher when particular clinical features that render the condition syndromic accompany. METHODS: In this study, we aimed to investigate the diagnostic yield of microarrays in the subgroup of individuals with non-syndromic ID/DD (NSID/NSDD). A total of 302 NSID/NSDD individuals who have undergone microarray analysis between October 2013 and April 2020 were included. Accompanying clinical data, including head circumference, delayed developmental areas, seizures and behavioural problems were collected and analysed separately in NSID and NSDD subgroups. RESULTS: The diagnostic yield of microarray analyses in NSID/NSDD was determined as 10.9% in NSID (10.7%) and in NSDD (11.1%). Presence of behavioural and epileptic problems did not contribute to the diagnostic yield. However, in the presence of macrocephaly, the contribution to diagnostic yield was statistically significant particularly in NSDD group. The most common pathogenic CNVs involved chromosomes 16, 15 and X. Lastly, we propose a Xq21.32q22.1 deletion as likely pathogenic in a child with isolated language delay and accompanying seizures. CONCLUSIONS: Particularly in neurodevelopmental diseases, microarrays are useful for establishing the diagnosis and detecting novel susceptibility regions. Future studies would accurately classify the herein presented variants of uncertain significance CNVs as pathogenic or benign.

Comparison of three different noninvasive ventilation strategies as initial respiratory support in very low birth weight infants with respiratory distress syndrome: A retrospective study.

BACKGROUND: There is inadequate evidence regarding which noninvasive ventilation (NIV) is superior for initial respiratory support of preterm infants with respiratory distress syndrome. OBJECTIVES: To compare the failure of noninvasive ventilation (NIV) and neonatal outcomes between nasal continuous positive airway pressure (NCPAP), bi-level positive airway pressure (BiPAP), and nasal intermittent positive pressure ventilation (NIPPV) as the initial respiratory support with less invasive surfactant administration (LISA) in very low birth weight (VLBW) infants. METHODS: Medical records of 419 VLBW infants born at 26-30weeks' gestation who did not require intubation in the delivery room and were initially supported with either NCPAP (n=221), BiPAP (n=101), or NIPPV (n=97) were retrospectively reviewed. The LISA approach was preferred in cases of surfactant requirement. The primary outcome was the failure of NIV within the first 72h of life. Failure of NIV was defined as the persistence or recurrence of one or more of the following: hypoxemia, respiratory acidosis, more than one episode of apnea requiring bag and mask ventilation or more than six episodes of apnea requiring stimulation over a 6-h period. Data were analyzed using univariate and multivariate logistic regression analysis. RESULTS: Failure of NIV within the first 72h of life was significantly higher in the NCPAP group (29.4%) compared with the BiPAP (12.9%) or NIPPV (12.4%) group (P<0.001). However, the BiPAP and NIPPV groups were not different in terms of NIV failure (P=0.91). Multivariable logistic regression analysis showed that antenatal steroid administration (OR: 0.49, 95% CI: 0.27-0.90; P=0.02) and gestational age˂28weeks (OR: 2.03, 95% CI: 1.18-3.49; P=0.01) were independent factors that influence failure of NIV within the first 72h of life. CONCLUSION: Compared with NCPAP, the use of NIPPV/BiPAP strategies for initial respiratory support can reduce the need for invasive ventilation in infants born at 26-30weeks' gestation.

Genetic IGF1R defects: new cases expand the spectrum of clinical features.

PURPOSE: We aimed to identify the phenotypic variability of IGF1R defects in a cohort of short children with normal GH secretion gathered through the last decade. PATIENTS AND METHODS: Fifty children (25 girls) with short stature and a basal/stimulated growth hormone (GH) over 10 ng/ml having either a low birth weight or microcephaly were enrolled. MLPA and then Sanger sequence analysis were performed to detect IGF1R defects. The auxological and metabolic evaluation were carried out in index cases and their first degree family members whenever available. RESULTS: A total of seven (14%) IGF1R defects were detected. Two IGF1R deletions and five heterozygous variants (one frameshift, four missense) were identified. Three (likely) pathogenic, one VUS and one likely benign were classified by using ACMG. All children with IGF1R defects had a height < - 2.5SDS, birth weight < - 1.4SDS, and head circumference < - 1.36SDS. IGF-1 ranged from - 2.44 to 2.13 SDS. One child with a 15q terminal deletion had a normal phenotype and intelligence, whereas low IQ is a finding in a case with missense variant. Two parents who carried IGF1R mutations had diabetes mellitus, hypertension and hyperlipidemia, one of whom also had hypergonadotropic hypogonadism. CONCLUSION: We found a deletion or variant in IGF1R in 14% of short children. Birth weight, head circumference, intelligence, dysmorphic features, IGF-1 levels and even height are not consistent among patients. Additionally, metabolic and gonadal complications may appear during adulthood, suggesting that patients should be followed into adulthood to monitor for these late complications.

Effect of withholding feeds on transfusion-related acute gut injury in preterm infants: a pilot randomized controlled trial.

Background: Several retrospective studies have reported an increase in necrotizing enterocolitis (NEC) during the 48 h following red blood cell (RBC) transfusion. Whether withholding enteral feeding during transfusion decreases the risk of transfusion-associated acute gut injury (TRAGI) in preterm infants is unclear.Study design and methods: In this pilot study, 112 preterm infants with gestational age ≤32 weeks and/or birth weight ≤1500 g were randomly assigned to withholding (NPO) or continuance of feeding (FED) during RBC transfusion. Primary outcome measure was development of NEC (stage ≥ 2) within 72 h of a transfusion and the change in abdominal circumference.Results: One hundred fifty-four transfusion episodes (74 NPO and 80 FED) were analyzed. Demographic characteristics were found to be similar in both groups. There was no difference in rates of NEC (0 versus 3.4%; p = .49) between the NPO and FED groups. The incidence of feeding intolerance was higher in the FED group; however, it was statistically insignificant (1.9 versus 6.8%, p = .36). Abdominal circumference remained similar in both groups in all three consecutive days following transfusion (p>.05).Conclusion: This pilot study does not support withholding feedings during transfusion but is not adequately powered to test the hypothesis that NPO decreases NEC rates. Adequately powered well-designed multicenter trials are still required.

The association of early postnatal weight loss with outcome in extremely low birth weight infants.

BACKGROUND: To compare outcomes of extremely low birth weight (ELBW) infants having different weight losses in the first 3 days of life. METHODS: One hundred and twenty six ELBW infants were evaluated retrospectively for weight loss percentages on the third day of life compared to their birth weight. We examined the weight loss on the third day of life compared to the birth weight for the ELBW infants and tested its association with mortality and morbidities. The mortality was subgrouped as overall mortality and mortality in the first 7 days of life. The morbidities were patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH) and bronchopulmonary dysplasia (BPD). BPD was defined as need for supplemental oxygen at 36 weeks' postconceptional age. We grouped the infants into four quartiles according to weight loss percentage on the third day of life: Group 1 (Quartile 1), infants with weight loss of 0-3% of birth weight; Group 2 (Quartile 2); infants with weight loss of 3.1-7.5%, Group 3 (Quartile 3), infants with weight loss of 7.51-12%; and Group 4 (Quartile 4), infants with weight loss of more than 12%. The mortality and morbidities were analyzed according to these groups and other risk factors. RESULTS: Overall mortality and mortality in the first 7 days of life were significantly higher in Groups 1 (36% and 27%) and 4 (43% and 24%), compared to Groups 2 (10% and 10%) and 3 (18% and 9%), respectively. CONCLUSION: Weight loss less than 3% and more than 12% was significantly associated with an increase in mortality. There was a positive correlation between weight loss on the third day of life and IVH. CONCLUSION: Inappropriate weight loss in ELBW infants is associated with increased mortality and IVH. Appropriate weight loss can improve outcomes in this population.

Vitamin D replacement ameliorates serum lipoprotein functions, adipokine profile and subclinical atherosclerosis in pre-menopausal women.

BACKGROUND AND AIMS: Low vitamin D (vitD) has been linked to increased cardiovascular (CV) risk, but the effects of vitD supplementation are not clarified. We evaluated the impact of vitD normalization on HDL cholesterol efflux capacity (CEC), which inversely correlates with CV risk, the proatherogenic serum cholesterol loading capacity (CLC), adipokine profile and subclinical atherosclerosis. METHODS AND RESULTS: Healthy premenopausal women with vitD deficiency (n = 31) underwent supplementation. Subclinical atherosclerosis was evaluated by flow-mediated dilation (FMD), pulse wave velocity (PWV) and augmentation index (AIx), measured with standard techniques. HDL CEC and serum CLC were measured by a radioisotopic and fluorimetric assay, respectively. Malondialdehyde (MDA) in HDL was quantified by the TBARS assay. Pre-ß HDL was assessed by 2D-electrophoresis. Serum adipokines were measured by ELISA. VitD replacement restored normal levels of serum 25-hydroxyvitamin D (25OHD) and significantly improved FMD (+4%; p < 0.001), PWV (-4.1%: p < 0.001) and AIx (-16.1%; p < 0.001). Total CEC was significantly improved (+19.5%; p = 0.003), with a specific increase in the ABCA1-mediated CEC (+70.8%; p < 0.001). HDL-MDA slightly but significantly decreased (-9.6%; p = 0.027), while no difference was detected in pre-ß HDL. No change was observed in aqueous diffusion nor in the ABCG1-mediated CEC. Serum CLC was significantly reduced (-13.3%; p = 0.026). Levels of adiponectin were increased (+50.6%; p < 0.0001) and resistin levels were decreased (-24.3%; p < 0.0001). After vitD replacement, an inverse relationship was found linking the ABCA1-mediated CEC with pre-ß HDL (r2 = 0.346; p < 0.001) and resistin (r2 = 0.220; p = 0.009). CONCLUSION: Our data support vitD supplementation for CV risk prevention.

Arthroscopic Technique for Treatment of Schatzker Type III Tibia Plateau Fractures Without Fluoroscopy.

Accurate reduction and maintenance of the stability with correct implant positioning is critical for surgical treatment of tibial plateau fractures. Our technique includes an arthroscopic reduction and fixation of Schatzker type III tibial plateau fractures with a bulls-eye screw placement without fluoroscopy control. With the arthroscopic guidance, an anterior cruciate ligament drill guide is placed and a K-wire sent to the midpoint of the depressed fragment through the guide at a 40° angle to the coronal axis of the tibia. A tunnel is created with the drill over the K-wire. The depressed fragment is further augmented with gentle impacts over the K-wire. After arthroscopic reduction control, an appropriate-sized iliac graft is pushed until it is below the depressed fragment. The targeting device is adjusted at 130° so that it is parallel to the joint line and a K-wire sent through the device so that it would pass just below the graft. The graft is then supported with cannulated screws sent over the K-wire. This technique provides an arthroscopic reduction of the chondral surface and precise placement of the rafting screws without fluoroscopy.

Proximal femoral nail shows better concordance of gait analysis between operated and uninjured limbs compared to hemiarthroplasty in intertrochanteric femoral fractures.

PURPOSE: The purpose of this study was to compare the results of pedobarographic gait analysis between the patients treated by proximal femoral nail or bipolar partial hemiarthroplasty due to intertrochanteric fractures. METHODS: Thirty-seven patients with a minimum 1-year follow-up who had been operated for intertrochanteric fractures were evaluated clinically, radiologically and with pedobarographic gait analysis. Proximal femoral nail had been performed to 21 patients (group A), whilst 16 patients had been operated by partial bipolar hemiarthroplasty (group B). Pedobarographic analysis was performed by measuring plantar pressure, force and contact area values in both static and dynamic manner. Pedobarographic results of operated limb were compared among groups. Same data's also were compared between operated and uninjured limbs in each group to determine any asymmetry on weight-bearing. RESULTS: Average follow-up period in group A and group B was 36 (12-56) and 30 (12-48) months, respectively. There were no statistically significant differences among groups in terms of age, gender, body mass index, type and side of fracture, follow-up period, leg length discrepancy and postoperative hip scores. When the pedobarographic results of operated limb were compared, group B showed much more plantar force and pressure values than group A, on both static and dynamic evaluations. If the evaluation was taken into consideration to comparison of pedobarographic results between operated and uninjured limbs in each group, we found asymmetry in static load bearing, caused by higher load on uninjured limb in both groups. However, there was no statistically significant asymmetry between operated and uninjured limbs in respect to dynamic pedobarographic parameters for patients in group A. On the contrary, operated limbs in group B exposed much more plantar force and pressure values than uninjured limbs, which indicated asymmetric weight-bearing on dynamic evaluation. CONCLUSIONS: Assessment of pedobarographic parameters can be another way of measuring the results of treatment in intertrochanteric fractures. Uninjured limbs of patients expose much more loading than operated limbs in postoperative static evaluation for both treatment options. However in dynamic evaluation, there is a better concordance of gait analysis between both limbs in patients operated by proximal femoral nail.

Precise placement of lag screws in operative treatment of trochanteric femoral fractures with a new guide system.

PURPOSE: We assessed the accuracy of a new guide system that we developed to place lag screws in the proper position with the minimum number of attempts for operative treatment of trochanteric femoral fractures. METHODS: A total of 55 consecutive trochanteric femoral fractures were treated with a cephalomedullary nail. The first 27 consecutive patients were treated with the standard operation (group A), while the new guide system was used in the last 28 consecutive patients (group B). The numbers of attempts to place K wires and the duration of surgery were noted. Accuracy of lag screw placement was evaluated by measuring the angle of deviation from the central axis of the femoral head. RESULTS: Deviation values ranged from -11̊ to +15̊ for the 27 cases in group A, with a median absolute deviation of 8̊±6̊. That in the 28 cases after the introduction of the new guide system (group B) ranged from -5̊ to +6̊, with a median absolute deviation of 0.5̊±3̊ (P<0.001). The total numbers of attempts to place lag screws and mean operation time decreased significantly after introduction of the new guide system (P<0.001). CONCLUSIONS: With this new guide system, we are able to insert lag screws successfully in the optimal position even in most unstable fractures. The present study indicated that this new guide system and nail facilitate accurate placement of lag screws in the appropriate position with the minimum number of attempts.

Interleukin-6 and C-reactive protein load in pre-storage and post-storage white blood cell-filtered red blood cell transfusions in premature infants.

OBJECTIVE: Leukocyte contamination during blood transfusion can cause many adverse effects. Filtration can be performed either at bedside during the transfusion or as pre-storage filtration. Pre-storage filtration is superior to bedside filtration because leukocytes are removed prior to storage, thus preventing further adverse effects associated with the storage of these cells. METHODS AND MATERIALS: One hundred and six infants were randomised into two groups: pre-storage filtration (group 1, n = 53) and bedside filtration (group 2, n = 53). C-reactive protein (CRP) and interleukin-6 (IL-6) levels were analysed within 24 h prior to the transfusion and 24 h after completion of the transfusion. RESULTS: In group 1, pre-transfusion median CRP and IL-6 levels were 2·95 (0·73-10·25) mg L(-1) and 8·59 (3·45-20·55) pg L(-1) , respectively, and post-transfusion median CRP and IL-6 levels were 2·28 (0·44-12·87) mg L(-1) and 6·62 (2·18-27·87) pg L(-1) , respectively. In group 2, pre-transfusion median CRP and IL-6 levels were 1·30 (0·40-7·84) mg L(-1) and 4·40 (2-17·12) pg L(-1) , respectively, and post-transfusion median CRP and IL-6 levels were 3·50 (0·50-7·85) mg L(-1) and 8·30 (3·48-23·75) pg L(-1) , respectively. There were no differences between pre-storage and post-storage leukoreduction average IL-6 and CRP levels in either group (P > 0·05 for both). Packed red blood cell (PRBC)-related necrotizing enterocolitis was detected in one infant in group 2. CONCLUSIONS: Because leukocytes in PRBC transfusions can be associated with many undesirable effects, leukoreduction is the best choice to prevent those effects. However, this method is still controversial. We demonstrated that using pre-storage and post-storage leukoreduction methods in erythrocyte transfusions did not change CRP or IL-6 levels, which are indicators of acute-phase response.

Risk factors for peritoneal dissemination of gastric cancer.

AIM: Tumor dissemination, lymphnode involvement and surgical resection technique are the most important factors affecting patient prognosis with gastric cancer. Peritoneal dissemination adversely affects the survival rate in patients. Microscopic peritoneal dissemination can be detected with peritoneal lavage cytological examination. Peroperatively detected microscopic peritoneal dissemination changes the treatment plan for patients and can be useful when selecting patients who should undergo adjuvant chemotherapy. METHODS: At the Trakya Universtity Faculty of Medicine, General Surgery Department, a 41-year-old patient who was macroscopic peritoneal dissemination during the dates January-December 2011 was included in the study. Perioperative peritoneal lavage was performed and cytological examination of peritoneal aspirate carried out. Using tumor markers the relationship between lymph node metastasis, prognostic type, tumor location and perineural invasion was investigated on the serum and peritoneal fluid. RESULTS: Forty-one patients were operated on; 10 of them (24.4%) had positive malignant cytology and 31 (75.7%) had negative cytology. Just 1 (7.2%) patient was found to have positive cytology out of 13 (31.7%) that did not have serous invasion. Of the 28 (68.3%) patients with serous invasion, 9 patients (32.1%) were found to have positive cytology. No significant pattern was detected in the carcino-embryionic antigen, cancer antigen 19-9 and AFP levels in both the positive and negative cytology serum and peritoneal lavage fluid. Of the 41 patients operated on 5 (12.2%) were found to have cardia dissemination and 13 (31.7%) were found to have dissemination located at the corpus. Peritoneal dissemination was found to be significantly high in gastric cancer located in the cardia and corpus. Fourteen (34.1%) of the patients had stage I and stage II cancer and 27 (65.9%) of patient's had cancer in stages III and IV. Just 1 (7.1%) patient with stage I or II cancer was found to have positive malignant cytology, however 9 (33.3%) patient's of stage III and IV gastric cancer patients were tested positively for malignant cytology. CONCLUSION: A positive relationship was detected in the positive peritoneal cell malignancy with cancer stage, age, invasion depth and tumor location in patients.

Comparison between electronic method and conventional method recording and follow-up of general surgery ward-round notes taken.

AIM: Patient anamneses and ward-rounds notes taken are two key elements which have been and will be used to ensure accurate and reliable sustainability at surgery services. In this study, we aimed to find a new method which is capable of better addressing the needs in this process, simplifying it and also saving time. We also targeted to compare this new method used by us with the method, also known as conventional method, having been used for years. METHODS: Thirty patients were included in the study. The prehospitalization anamneses of the patients were taken using the two methods and the durations were recorded separately for the two methods. Thereafter, the patients were visited by two methods in the morning on each day of their stay. The durations were recorded daily and separately for the two methods. The durations were statistically evaluated separately for the anamneses and ward-round notes taken. RESULTS: Evaluations showed that the method using hand terminal (1.2250 minutes) is more advantageous in terms of duration in recording ward-round scores than the conventional method (1.3853 minutes). It was founded that in regard to the duration, the average duration of manual anamnesis taking (16.3350 minutes) is higher than that of taking anamnesis by means of hand terminal (15.4733 minutes). Furthermore, it was also seen that the use of this new technique eliminated the problems previously experienced in data transfer, access to historical data etc. CONCLUSION: In conclusion, this method that is tested by use of hand terminal is more advantageous than the conventional method in terms of time saving and accurate data transfer. It is our opinion that it will provide advantages in many more aspects if it is worked on.

Preeclampsia is an independent risk factor for spontaneous intestinal perforation in very preterm infants.

BACKGROUND: Spontaneous intestinal perforation (SIP) is an important surgical emergency in preterm infants. AIMS: To evaluate the effect of maternal preeclampsia on development of SIP in premature infants. STUDY DESIGN: Retrospective observational study in a large tertiary neonatal intensive care unit. SUBJECTS: The preterm infants of ≤32 weeks of gestational age and birthweight ≤1500 g who were hospitalized were enrolled. OUTCOME MEASURES: The primary outcome was to determine the association between preeclampsia and SIP. RESULTS: A total of 22 infants had SIP diagnosis. The incidence of SIP in infants born to preeclamptic mothers (6.2%) was significantly higher compared with those born to normotensive mothers (0.2%). In multinominal logistic regression model, preeclampsia was found to be an independent risk factor of SIP with an odds ratio of 13.5 (95% confidence interval 2.82-65.1). CONCLUSIONS: Maternal preeclampsia seemed to be an independent risk factor for development of SIP in premature infants.

Fryns anophthalmia-plus syndrome: two rare cases.

Fryns anophthalmia-plus syndrome is a rare syndrome with clinical diversity primarily including anophthalmia/microphthalmia, facial clefts, cleft lip/palate, ear and nasal deformities. Here we present two different cases of APS with anopthalmia/microphthalmia, cleft palate, low set ears, ventriculomegaly and one of which had intestinal non-fixation anomaly not described in the literature before.

Case report: partial trisomy 4q27q35 syndrome.

Partial trisomy 4q is a rare chromosomal abnormality which results in variable clinical features, often including growth and developmental delay, mental retardation and dysmorphic features. We herein report a newborn with the diagnosis of partial trisomy 4q with Hirschsprung's disease who was monitored in neonatal intensive care unit. This is the first report of partial trisomy 4q27q35 with accompanying Hirschsprung's disease.