Diversity of kidney care referral pathways in national child health systems of 48 European countries.

Background: Primary, secondary and tertiary healthcare services in Europe create complex networks covering pediatric subspecialties, sociology, economics and politics. Two surveys of the European Society for Paediatric Nephrology (ESPN) in 1998 and 2017 revealed substantial disparities of kidney care among European countries. The purpose of the third ESPN survey is to further identify national differences in the conceptualization and organization of European pediatric kidney health care pathways during and outside normal working hours. Methods: In 2020, a questionnaire was sent to one leading pediatric nephrologist from 48 of 53 European countries as defined by the World Health Organization. In order to exemplify care pathways in pediatric primary care nephrology, urinary tract infection (UTI) was chosen. Steroid sensitive nephrotic syndrome (SSNS) was chosen for pediatric rare disease nephrology and acute kidney injury (AKI) was analyzed for pediatric emergency nephrology. Results: The care pathways for European children and young people with urinary tract infections were variable and differed during standard working hours and also during night-time and weekends. During daytime, UTI care pathways included six different types of care givers. There was a shift from primary care services outside standard working hours to general outpatient polyclinic and hospital services. Children with SNSS were followed up by pediatric nephrologists in hospitals in 69% of countries. Patients presenting with community acquired AKI were admitted during regular working hours to secondary or tertiary care hospitals. During nights and weekends, an immediate shift to University Children's Hospitals was observed where treatment was started by intensive care pediatricians and pediatric nephrologists. Conclusion: Gaps and fragmentation of pediatric health services may lead to the risk of delayed or inadequate referral of European children with kidney disease to pediatric nephrologists. The diversity of patient pathways outside of normal working hours was identified as one of the major weaknesses in the service chain.

Continuous Kidney Replacement Therapy Practices in Pediatric Intensive Care Units Across Europe.

Importance: Continuous kidney replacement therapy (CKRT) is the preferred method of kidney support for children with critical illness in pediatric intensive care units (PICUs). However, there are no data on the current CKRT management practices in European PICUs. Objective: To describe current CKRT practices across European PICUs. Design, Setting, and Participants: This cross-sectional survey of PICUs in 20 European countries was conducted by the Critical Care Nephrology Section of the European Society of Pediatric and Neonatal Intensive Care from April 1, 2020, to May 31, 2022. Participants included intensivists and nurses working in European PICUs. The survey was developed in English and distributed using SurveyMonkey. One response from each PICU that provided CKRT was included in the analysis. Data were analyzed from June 1 to June 30, 2022. Main Outcome and Measures: Demographic characteristics of European PICUs along with organizational and delivery aspects of CKRT (including prescription, liberation from CKRT, and training and education) were assessed. Results: Of 283 survey responses received, 161 were included in the analysis (response rate, 76%). The attending PICU consultant (70%) and the PICU team (77%) were mainly responsible for CKRT prescription, whereas the PICU nurses were responsible for circuit setup (49%) and bedside machine running (67%). Sixty-one percent of permanent nurses received training to use CKRT, with no need for certification or recertification in 36% of PICUs. Continuous venovenous hemodiafiltration was the preferred dialytic modality (51%). Circuit priming was performed with normal saline (67%) and blood priming in children weighing less than 10 kg (56%). Median (IQR) CKRT dose was 35 (30-50) mL/kg/h in neonates and 30 (30-40) mL/kg/h in children aged 1 month to 18 years. Forty-one percent of PICUs used regional unfractionated heparin infusion, whereas 35% used citrate-based regional anticoagulation. Filters were changed for filter clotting (53%) and increased transmembrane pressure (47%). For routine circuit changes, 72 hours was the cutoff in 62% of PICUs. Some PICUs (34%) monitored fluid removal goals every 4 hours, with variation from 12 hours (17%) to 24 hours (13%). Fluid removal goals ranged from 1 to 3 mL/kg/h. Liberation from CKRT was performed with a diuretic bolus followed by an infusion (32%) or a diuretic bolus alone (19%). Conclusions and Relevance: This survey study found a wide variation in current CKRT practice, including organizational aspects, education and training, prescription, and liberation from CKRT, in European PICUs. This finding calls for concerted efforts on the part of the pediatric critical care and nephrology communities to streamline CKRT education and training, research, and guidelines to reduce variation in practice.

Incidence of Type 1 Diabetes Mellitus and Characteristics of Diabetic Ketoacidosis in Children and Adolescents during the First Two Years of the COVID-19 Pandemic in Vojvodina.

Background and Objectives: The COVID-19 pandemic has led to significant changes globally, which has also affected patients with type 1 diabetes mellitus (T1DM). This study aimed to determine the incidence of T1DM and the characteristics of diabetic ketoacidosis (DKA) during the pandemic comparing it to pre-pandemic period. Materials and Methods: Data from patients <19 years with newly diagnosed T1DM between 1st January 2017 and 31st December 2021 from four regional centers in Vojvodina were retrospectively collected and analyzed. Results: In 2021, the highest incidence of T1DM in the last five years was recorded, 17.3/100,000. During the pandemic period (2020−2021), there were 99 new-onset T1DM, of which 42.4% presented in DKA, which is significantly higher than in the pre-pandemic period (34.1%). During the pandemic, symptom duration of T1DM lasted significantly longer than before the COVID-19 period. At the age of 10−14 years, the highest incidence of T1DM and COVID-19, the highest frequency rate of DKA, and severe DKA were observed. Conclusions: The pandemic is associated with a high incidence rate of T1DM, longer duration of symptoms of T1DM, a high frequency of DKA, and a severe DKA at diagnosis. Patients aged 10−14 years are a risk group for the occurrence of T1DM with severe clinical presentation. Additional studies are needed with a longer study period and in a wider geographical area, with data on exposure to COVID-19 infection, the permanence of new-onset T1DM, and the psychosocial impact of the pandemic.

Real World Overall Survival of Patients With Metastatic Renal Cell Carcinoma Treated With Only Available Sunitinib and Pazopanib in First-Line Setting.

Background: The emerging new standard of care for metastatic clear cell renal carcinoma (mRCC) becomes a challenge when access to new drugs is limited. In Serbia, sunitinib and pazopanib are the only available first-line therapies. The second-line treatment for mRCC has never been and is still not available. We aimed to assess overall survival (OS) in patients with mRCC who received first-line sunitinib or pazopanib when access to second-line treatment was not available. Methods: This retrospective observational study analyzed data from a nationally representative cohort of 759 patients who started on first-line sunitinib or pazopanib between 1 January 2012 and 30 June 2019, in 4 centers in Serbia. The data cut-off date was 31 December 2019. Key eligibility criteria were clear cell RCC histology, measurable metastatic disease, performance status 0 or 1, and the Memorial Sloan Kettering Cancer Center favorable or intermediate prognosis. The primary outcome was OS from the start of first-line treatment to death or data cut-off date. Results: The study population included 759 patients with mRCC who started with first-line sunitinib (n = 673; [88.7%]) or pazopanib (n = 86; [11.3%]). Overall, the mean age was 61.0 ± 9.7 years at treatment baseline, and 547 (72%) were men. mRCC was primarily diagnosed in 230 (30%) patients, and most of them underwent cytoreductive nephrectomy prior to systemic therapy (n = 181 [79%]). Additional treatment of metastases prior to and/or during treatment was used in 169 patients (22.3%). Grade 3 and 4 adverse events occurred in 168 (22.1%) and 47 patients (6.2%), respectively, and treatment was permanently stopped because of toxicity in 41 (6.9%). The OS was calculated from the start of first-line treatment, and the median follow-up was 14 months (range, 0-97). The median OS in the entire cohort was 17 months (95% CI, 14.6-19.4). Conclusions: With only available sunitinib and pazopanib in first-line treatment, modest improvements are seen in the overall survival of patients with mRCC in real world clinical practice. In circumstances of limited availability of cancer medicines, our results can contribute to accelerating patient access to novel cancer therapies that have been shown to prolong survival in mRCC.

Human anterior pituitary's ACTH cells during the aging process: immunohistochemic and morphometric study.

Corticotrophs produce a hormone that stimulates the adrenal gland cortex to secrete glucocorticoids, which in turn have effects on carbohydrate and protein metabolism. Quantification, morphological characteristics, and distribution of corticotrophs in the anterior pituitary and changes in the number and shape of the cells during aging have been examined using immunohistochemical and morphometric methods. The material consisted of 14 anterior pituitaries taken from cadavers at routine autopsy. The tissue was processed by standard histological procedure and the obtained slices were stained by the monoclonal anti-ACTH antibody for corticotrophs identification. Digital images of stained histological sections were analyzed using the morphometric method with the Image J system. The volume density of ACTH positive cells was determined. The cases were classified into three age groups. One-way ANOVA showed that the volume density of the corticotrophs was significantly higher in the second and third group in relation to the first group. The difference in the volume densities of the corticotrophs between the genders was not significant. Morphometric and statistical analyses demonstrated a significant positive correlation between the corticotrophs volume densities and the age of the evaluated cases. Linear regression showed that age significantly predicts corticotrophs volume density. Corticotrophs significantly increase during the life span.

Morphometric analysis of the epineurial and endoneurial blood vessels of the human sciatic nerve in relation to aging.

The aim of this research is to perform an analysis of the epineurial and endoneurial blood vessels in relation to aging. The research is conducted on samples of the human sciatic nerve of 12 case (age from 27 to 89). The histological sections are stained by streptavidin-biotin method of detecting the presence of Type IV collagen. After morphometric analysis the following stereological parameters have been calculated: the number of blood vessels per unit of area, the volume density of the blood vessels and the surface density of the blood vessels of the epineurium and endoneurium. An additional diameter measurement is performed for the endoneural blood vessels. In order to perform a more detailed analysis, the cases were classified into three age groups, the first (27-48 years), the second (49-70 years) and, the third (over 70 years). The bivariate correlation analysis showed that the number of blood vessels of the endoneurium, their volume and surface densities in relation to age produced a statistically significant positive correlation. One Way ANOVA test demonstrated a statistically significant increase in the number of endoneurial blood vessels in the age group III when compared the age group I and, in addition, it showed a significant decrease in the diameter of the age group II when compared to the age group I. Paired t - test shows a statistically significant higher number of endoneurial blood vessels in relation to the epineurial, namely, in the age group III. The volume and surface density of the epineurial blood vessels is significantly higher than the endoneurial in both the I and II age group. Age brings about significant changes of the endoneurial vascular network of the sciatic nerve due to the increase in density of the endoneurial blood vessels, their volume and surface densities. Consequently, in the cases older than 70 years, the number of endoneurial blood vessels significantly exceeds the number of epineurial blood vessels.

Kawasaki Disease Complicated with Cerebral Vasculitis and Severe Encephalitis.

We report a case of a 7-year-old boy with Kawasaki disease (KD) complicated with cerebral vasculitis and encephalitis. The patient was admitted with signs of encephalopathy, seizures, and coma. The diagnosis of KD was made on the 2nd day of hospitalization based on the clinical features (fever >5 days, maculopapular rash, nonpurulent conjunctivitis, fissured lips, and cervical adenopathy). Brain magnetic resonance imaging findings suggested cerebral vasculitis. Treatment with intravenous immunoglobulin was followed by mild improvement. After a single dose of immunoglobulin, pulse methylprednisolone therapy was started resulting in gradual improvement of consciousness and eventual complete motor and cognitive function recovery with regression of brain magnetic resonance lesions. KD can present with marked neurological symptomatology. Therefore, it should be considered in the differential diagnosis of encephalitis and encephalopathy etiologies in children.

Attitudes Toward Organ Donation and Transplantation Among Transplant-Related Health Care Workers and the Local Population of Montenegro.

OBJECTIVES: The aim of this research was to determine the attitudes of transplant-related health care workers and the local population of Montenegro toward organ donation and transplantation. MATERIALS AND METHODS: Our study included 200 transplant-related health care professionals (from the Clinical Center of Montenegro, the only transplant hospital in the country) and 200 volunteers from Podgorica (the capital of Montenegro). Their attitudes were evaluated using an anonymous, self-administered, multiple-choice questionnaire. RESULTS: Most health care workers would donate their organs only on specific occasions (43.6%), whereas the general population was divided between willingness to donate only on specific occasions and the need to consider the decision of donating (34.6% each). Both groups of respondents predominantly claimed that they would donate their organs to any potential recipient, regardless of sensory or physical disability. A positive opinion regarding the promotion of organ donation, as well as the need for legal regulation of the transplant process, was noted in both groups of responders. CONCLUSIONS: There is a need to increase the generosity of the Montenegrin population and its health care workers regarding organ donation at all times and not exclusively on specific occasions.

Performance of the new clinical case definitions of pertussis in pertussis suspected infection and other diagnoses similar to pertussis.

BACKGROUND: In an effort to improve the pertussis diagnosis, the Global Pertussis Initiative (GPI) proposed an algorithm of the signs/symptoms of pertussis for three age groups: 0-3 months, 4 months to 9 years, and ≥10 years of age. METHODS: We evaluated the accuracy of the clinical case definitions for pertussis proposed by the GPI using laboratory-confirmed pertussis as a reference standard for four groups: clinically suspected pertussis without comorbidity; asthma exacerbation; allergic constitution, and other diagnoses (bronchitis, bronchiolitis, laryngitis, and tracheitis). We included only patients who fulfilled one or more criteria of clinical case definitions for the age groups (0-3 months, 4 months-9 years, and ≥10 years of age). The data for this prospective epidemiological study were collected between 1st January 2013-31st December 2016 at the outpatients and inpatients health care settings in the South Backa District of Autonomous Province of Vojvodina, Serbia. We evaluated accuracy of the certain sign and symptom combinations of GPI case definitions based on their sensitivity, specificity, and likelihood ratios. RESULTS: A total of 1043 participants were included, with 306 (29.3%) laboratory-confirmed pertussis cases. In patients aged 0-3 months, whoop and apnoea associated with laboratory confirmation of pertussis. In patients aged 4 months-9 years with a pertussis suspicion infection or with one of the other diagnoses, the highest accuracy was found for whoop combined with apnoea or post-tussive emesis. In patients aged 10 years and older, several different sign and symptom combinations were associated with an increased risk of pertussis among all enrolment diagnoses. There were fewer hospitalizations among the fully vaccinated children than in partly or unvaccinated children aged 4 months to 6 years (20.7% vs. 60.0%, p = 0.017). CONCLUSIONS: The numerous sign and symptom combinations in the observed case definitions were good predictors for laboratory-confirmed pertussis among all enrolment diagnoses, therefore suggesting the necessity for increased awareness of possibility for pertussis in patients with certain pertussis-like medical conditions.

Serum glutathione S-transferase Pi as predictor of the outcome and acute kidney injury in premature newborns.

BACKGROUND: The incidence of acute kidney injury (AKI) among the neonates treated at the Neonatal Intensive Care Unit is high with high mortality rates. Glutathione S-transferase (GST) class Pi plays an important role in the protection of cells from cytotoxic and oncogenic agents. The aim of the study was to examine whether the levels of serum glutathione S-transferase Pi (GST Pi) determined after birth have any predictive value for the outcome and development of AKI in premature neonates. METHODS: The prospective study included 36 premature neonates. The data about morbidity was gathered for all the neonates included in the study. The blood samples were taken in the first 6 h of life and GST Pi levels were measured. RESULTS: The mean values and standard deviations of GST Pi among the neonates who died and who survived were 1.904 ± 0.4535 vs 1.434 ± 0.444 ng/ml (p = 0.0128). Logistic regression revealed a statistically significant, positive correlation between GST Pi levels and death (p = 0.0180, OR7.5954; CI 1.4148-40.7748).The mean value of GST Pi levels in the neonates with AKI was higher than in neonates without AKI (p = 0.011). CONCLUSIONS: The conclusion of our study is that high levels of serum GST Pi in the first 6 h after birth are associated with an increased mortality and development of AKI in prematurely born neonates.

Etiology and Outcome of Severe Apparent Life-Threatening Events in Infants.

INTRODUCTION: An apparent life-threatening event (ALTE) is defined as "an episode that is frightening to the observer and is characterized by some combination of apnea, color change, marked change of muscle tone, choking, or gagging." OBJECTIVE: The aims of this study were to determine etiology and outcome of severe ALTE (requiring resuscitation measures) and to review diagnostic approaches in infants hospitalized after such an episode of ALTE. METHODS: Retrospective analysis included patients hospitalized at the Intensive Care Unit, Institute of Child and Youth Healthcare of Vojvodina, after an episode of severe ALTE over a 4-year period. RESULTS: The study included 23 infants, 18 male (78.3%), and 5 female (21.7%). The average age at presentation was 78 days (1 day to 11 months). In 8 infants (34.7%), ALTE resulted in death. The most frequent conditions after diagnostic evaluation were lower respiratory tract infections (39.1%), intracranial and extracranial hemorrhages (13.0%), and central nervous system infections (8.6%). The cause remained unknown in 8.7% of cases. Initial investigations included complete blood cell count, C-reactive protein or procalcitonin, blood gasses, lactate, electrolytes, glucose, blood culture, urinalysis, and chest x-ray. CONCLUSIONS: Apparent life-threatening event represents a diverse disorder. Lower respiratory tract infections and neurological disorders were the most common established etiology. Prematurity and congenital heart diseases stood out as important risk factors. Diagnostic evaluation varied according to suspected cause and trigger factors.

Biallelic variants in WARS2 encoding mitochondrial tryptophanyl-tRNA synthase in six individuals with mitochondrial encephalopathy.

Mitochondrial protein synthesis involves an intricate interplay between mitochondrial DNA encoded RNAs and nuclear DNA encoded proteins, such as ribosomal proteins and aminoacyl-tRNA synthases. Eukaryotic cells contain 17 mitochondria-specific aminoacyl-tRNA synthases. WARS2 encodes mitochondrial tryptophanyl-tRNA synthase (mtTrpRS), a homodimeric class Ic enzyme (mitochondrial tryptophan-tRNA ligase; EC 6.1.1.2). Here, we report six individuals from five families presenting with either severe neonatal onset lactic acidosis, encephalomyopathy and early death or a later onset, more attenuated course of disease with predominating intellectual disability. Respiratory chain enzymes were usually normal in muscle and fibroblasts, while a severe combined respiratory chain deficiency was found in the liver of a severely affected individual. Exome sequencing revealed rare biallelic variants in WARS2 in all affected individuals. An increase of uncharged mitochondrial tRNATrp and a decrease of mtTrpRS protein content were found in fibroblasts of affected individuals. We hereby define the clinical, neuroradiological, and metabolic phenotype of WARS2 defects. This confidently implicates that mutations in WARS2 cause mitochondrial disease with a broad spectrum of clinical presentation.

Peritoneal Dialysis in Very Low Birth Weight Neonates.

BACKGROUND: The aim of this retrospective study is to evaluate clinical characteristics and outcomes of very low birth weight (VLBW) neonates with acute kidney injury (AKI) treated with peritoneal dialysis (PD). METHODS: This retrospective study included 10 VLBW neonates treated with PD. Intravenous (IV) cannula and umbilical venous catheter were used for the peritoneal access. RESULTS: Mean age at the moment of starting PD was 14.9 ± 9.3 days. Mean body weight (BW) was 825 ± 215 g. The average gestational age was 26.3 ± 1.1 weeks. The average duration of dialysis was 20.5 ± 14.7 h. The average ultrafiltration was 7.7 ± 4.2 mL/kg/h. At the moment of starting PD, the average BW was 302 ± 317g (22 ± 13%), higher than at birth (in patients who had PD started in first 2 weeks of their lives) or higher than the BW before AKI was diagnosed (patients who had PD started when they were older than 2 weeks). The main cause of AKI was sepsis (n = 8/10). Dialysate leak was registered in 2 patients, 1 patient had peritonitis and the other had a blocked PD catheter. Six patients died during PD (severe sepsis), 1 died due to hypoxic encephalopathy and coma, and 2 patients survived. One patient (with hypoxic encephalopathy and coma) died 10 days after PD was stopped due to sepsis. The overall mortality was 80%. CONCLUSION: Acute PD is still an appropriate treatment choice for VLBW neonates with AKI. In VLBW neonates, PD can be performed with an improvised PD system and catheters.

Acute kidney injury in premature newborns-definition, etiology, and outcome.

BACKGROUND: Neonatal acute kidney injury (AKI) is common and is associated with poor outcomes. New criteria for the diagnosis of AKI were introduced based on the increase in serum creatinine (SCr) levels and/or reduction of urine output (UOP). Yet, there is no generally accepted opinion so far, which criteria (whether SCr, UOP, or their combination) are the most appropriate to diagnose neonatal AKI. METHODS: The retrospective study included 195 prematurely born neonates who fulfilled all inclusion criteria (with at least two SCr measurements). In all the neonates included in the study, AKI was diagnosed using three different definitions: (1) SCr criteria (an increase in SCr values of ≥0.3 mg/dl), (2) UOP criteria (UOP < 1.5 ml/kg/h), and (3) SCr + UOP criteria. RESULTS: Out of all of the patients the study included, 85 (44%) were diagnosed with AKI. The neonates who had AKI had a significantly lower gestational age, birth weight, and Apgar score, longer duration of mechanical ventilation, and a higher mortality rate. SCr + UOP criteria showed higher sensitivity for prediction of death compared to SCr or UOP alone (p = 0.0008, 95% CI 0.040-0.154, and p = 0.0038, 95% CI 0.024-0.125, respectively). If only SCr or only UOP criterion are used, they fail to identify AKI in 61 and 67%, respectively. AKI was an independent risk factor for death (OR 7.4875; CI 3.1887-17.5816). CONCLUSIONS: Similar to other studies, our data showed that neonates with AKI have worse outcome. Neonatal AKI defined based on SCr + UOP criteria is a better predictor of death than neonatal AKI defined based only on the SCr or UOP criteria. Also, by using SCr + UOP criteria for diagnosing neonatal AKI, more patients with AKI are recruited than when only one of those criteria is used.

Analysis of Linear Antibody Epitopes on Factor H and CFHR1 Using Sera of Patients with Autoimmune Atypical Hemolytic Uremic Syndrome.

INTRODUCTION: In autoimmune atypical hemolytic uremic syndrome (aHUS), the complement regulator factor H (FH) is blocked by FH autoantibodies, while 90% of the patients carry a homozygous deletion of its homolog complement FH-related protein 1 (CFHR1). The functional consequence of FH-blockade is widely established; however, the molecular basis of autoantibody binding and the role of CFHR1 deficiency in disease pathogenesis are still unknown. We performed epitope mapping of FH to provide structural insight in the autoantibody recruitment on FH and potentially CFHR1. METHODS: Eight anti-FH positive aHUS patients were enrolled in this study. With overlapping synthetic FH and CFHR1 peptides, we located the amino acids (aa) involved in binding of acute and convalescence stage autoantibodies. We confirmed the location of the mapped epitopes using recombinant FH domains 19-20 that carried single-aa substitutions at the suspected antibody binding sites in three of our patients. Location of the linear epitopes and the introduced point mutations was visualized using crystal structures of the corresponding domains of FH and CFHR1. RESULTS: We identified three linear epitopes on FH (aa1157-1171; aa1177-1191; and aa1207-1226) and one on CFHR1 (aa276-290) that are recognized both in the acute and convalescence stages of aHUS. We observed a similar extent of autoantibody binding to the aHUS-specific epitope aa1177-1191 on FH and aa276-290 on CFHR1, despite seven of our patients being deficient for CFHR1. Epitope mapping with the domain constructs validated the location of the linear epitopes on FH with a distinct autoantibody binding motif within aa1183-1198 in line with published observations. SUMMARY: According to the results, the linear epitopes we identified are located close to each other on the crystal structure of FH domains 19-20. This tertiary configuration contains the amino acids reported to be involved in C3b and sialic acid binding on the regulator, which may explain the functional deficiency of FH in the presence of autoantibodies. The data we provide identify the exact structures involved in autoantibody recruitment on FH and confirm the presence of an autoantibody binding epitope on CFHR1.

Morphometric analysis of the folliculostellate cells and luteinizing hormone gonadotropic cells of the anterior pituitary of the men during the aging process.

The aim of this research was to quantify the changes in the morphology and density of the anterior pituitary folliculostellate (FS) and luteinizing hormone (LH) cells. Material was tissue of the pituitary gland of the 14 male cadavers. Tissue slices were immunohistochemically stained with monoclonal anti-LH antibody and polyclonal anti-S100 antibody for the detection of LH and FS cells, respectively. Digital images of the stained slices were afterwards morphometrically analyzed by ImageJ. Results of the morphometric analysis showed significant increase of the FS cells volume density in cases older than 70 years. Volume density of the LH cells did not significantly change, whereas their area significantly increased with age. Nucleocytoplasmic ratio of the LH cells gradually decreased and became significant after the age of 70. Finally, volume density of the FS cell significantly correlated with LH cells area and nucleocytoplasmic ratio. From all above cited, we concluded that in men, density and size of the FS cells increase with age. Long-term hypertrophy of the LH cells results in their functional decline after the age of 70. Strong correlation between FS cells and LH cells morphometric parameters might point to age-related interaction between these two cell groups.

Severe neonatal subgaleal hemorrhage as the first presentation of hemophilia A.

INTRODUCTION: Subgaleal hemorrhage is a rare but potentially fatal birth trauma. It is caused by rupture of the emissary veins (connections between the dural sinuses and scalp veins), followed by the accumulation of blood between the epicranial aponeurosis and the periosteum. Usually, it is associated with instrumental delivery (vacuum extraction, forceps delivery), but it may also occur spontaneously, suggesting the possibility of congenital bleeding disorder. CASE OUTLINE: A full term male neonate was born at 40 weeks gestation by spontaneous vaginal delivery, with birth weight of 3,700 g. The Apgar scores were 9 and 10 at 1 and 5 minutes, respectively. At the age of 23 hours, the baby became pale and lethargic. Large fluctuant swelling on his head was noted. He developed severe anemia and hypovolemia as a result of massive subgaleal hemorrhage. After successful treatment, the baby fully recovered. Follow-up and further evaluation revealed hemophilia A as a result of a de novo mutation. CONCLUSION: This case illustrates that subgaleal hemorrhage may be the first presentation of hemophilia A. Infants without obvious risk factors for developing subgaleal hemorrhage should be evaluated for congenital bleeding disorder. Successful outcome in affected infants requires early diagnosis, careful monitoring and prompt treatment.

Urinary kidney injury molecule-1 rapid test predicts acute kidney injury in extremely low-birth-weight neonates.

BACKGROUND: The new urinary and serum biomarkers are discovered and are being investigated. With them we can diagnose acute kidney injury (AKI) faster and more precisely and they also have a significant role in the outcome prediction. METHODS: The study included 22 extremely low-birth-weight neonates who were hospitalized in the neonatal intensive care units. They were divided into two groups based on serum creatinine (SCr) level-with and without AKI. Detection and quantification of urinary kidney injury molecule-1 (uKIM-1) was done on the third day of life, using commercially available KIM-1 rapid test. Subsequently, measurements were repeated only in subjects who were diagnosed with AKI, at different values of SCr. RESULTS: Logistic regression analysis showed that AKI is an independent risk factor for mortality. In a group of neonates with AKI, 50% of neonates administered the KIM-1 rapid test showed positive findings. KIM-1 rapid test was positive in patients with a wide range of SCr levels (range of 78.73-385 µmol/l), but all subjects had oliguria and died in the next 24 h. CONCLUSION: KIM-1 is a significant predictor of death. On the other hand, our study failed to prove that KIM-1 rapid test has any significance for early prediction of AKI.