Functional gastrointestinal disorders in children: a single centre experience.

Functional gastrointestinal disorders in childhood (FGIDs) constitute a significant time-consuming clinical problem for healthcare practitioners, and they carry an important psychosocial burden for patients and their families. The aim of this study was to characterize etiology, clinical features, and interventions in a paediatric cohort of patients with FGIDs, who were referred to a tertiary care university-affiliated centre. Methods A retrospective study of children aged 1-15 years old referred to the Clinic for Children's Diseases, University Clinical Center Tuzla, from January 2022 to December 2022, who fulfilled criteria for FGIDs (n=209), were divided in three groups: 0-3, 4-10 and 11-15 years old. Demographic characteristics, number of examinations, duration of symptoms, initial diagnosis, hospital evaluation and outcomes of each child were collected. Results During the study period, 670 patients were referred to a gastroenterologist, out of whom 209 (31.2%) fulfilled the criteria for FGIDs, with median age of 8.0 years. Females were predominant in all groups (p=0.0369). Children aged 4 to 10 years were significantly more frequent (p<0.0001). A median duration of symptoms was one year. Functional constipation was the most common diagnosis, 99 (47.4%), followed by functional abdominal pain not otherwise specified, 67 (37.2%), and functional dyspepsia, 25 (12.0%). Fifty-two percent of patients did not require further follow-up by the gastroenterologist. Conclusion Although FGDIs are frequent, they are not well accepted neither among patients nor physicians. Extensive diagnostic procedures are often unnecessary and the cessation of specialized care follow-up is possible in a significant number of cases.

Predictors of adverse short-term outcomes in late preterm infants.

BACKGROUND: Infants born between 34 weeks and 36 weeks and 6 days of gestation are defined as late preterm infants (LPIs), and they account for approximately 74% of all premature births. Preterm birth (PB) remains the leading cause of infant mortality and morbidity worldwide. AIM: To analyse short-term morbidity and mortality and identify predictors of adverse outcomes in late preterm infants. PATIENTS AND METHODS: In this retrospective study, we evaluated adverse short-term outcomes of LPIs admitted to the Intensive Care Unit (ICU), Clinic for Children's Diseases, University Clinical Center Tuzla, between 01.01.2020 and 31.12.2022. The analysed data included sex, gestational age, parity, birth weight, Apgar score (i.e., assessment of vitality at birth in the first and fifth minutes after birth), and length of hospitalization in NICU, as well as short-term outcome data. Maternal risk factors we observed were: age of mother, parity, maternal morbidity during pregnancy, complications and treatment during pregnancy. LPIs with major anatomic malformations were excluded from the study. Logistic regression analysis was used to identify risk factors for neonatal morbidity among LPIs. RESULTS: We analysed data from 154 late preterm newborns, most of whom were male (60%), delivered by caesarean Sect. (68.2%) and from nulliparous mothers (63.6%). Respiratory complications were the most common outcome among all subgroups, followed by CNS morbidity, infections and jaundice requiring phototherapy. The rate of almost all of the complications in the late-preterm group decreased as gestational age increased from 34 to 36 weeks. Birth weight (OR: 1,2; 95% CI: 0,9 - 2,3; p = 0,0313) and male sex (OR: 2,5; 95% CI: 1,1-5,4; p = 0,0204) were significantly and independently associated with an increased risk for respiratory morbidity, and gestational weeks and male sex were associated with infectious morbidity. None of the risk factors analysed herein were predictors of CNS morbidity in LPIs. CONCLUSION: A younger gestational age at birth is associated with a greater risk of short-term complications among LPIs, thus highlighting the need for increased knowledge about the epidemiology of these late preterm births. Understanding the risks of late preterm birth is critical to optimizing clinical decision-making, enhancing the cost-effectiveness of endeavours to delay delivery during the late preterm period, and reducing neonatal morbidity.

Disease causing mutation (P178L) in mitochondrial transcription factor A results in impaired mitochondrial transcription initiation.

Mitochondrial transcription factor A (TFAM) is essential for the maintenance, expression, and packaging of mitochondrial DNA (mtDNA). Recently, a pathogenic homozygous variant in TFAM (P178L) has been associated with a severe mtDNA depletion syndrome leading to neonatal liver failure and early death. We have performed a biochemical characterization of the TFAM variant P178L in order to understand the molecular basis for the pathogenicity of this mutation. We observe no effects on DNA binding, and compaction of DNA is only mildly affected by the P178L amino acid change. Instead, the mutation severely impairs mtDNA transcription initiation at the mitochondrial heavy and light strand promoters. Molecular modeling suggests that the P178L mutation affects promoter sequence recognition and the interaction between TFAM and the tether helix of POLRMT, thus explaining transcription initiation deficiency.

Multivisceral Resection with Performing a Double Roux-en-Y Reconstruction for Advanced Gastric Cancer.

Background. The role of multivisceral resection, in the setting of locally advanced gastric cancer, is still debated. Previous studies have reported a higher risk for perioperative morbidity and mortality, with limited objective benefit in terms of survival. Patient. A male patient, 55 years old, was admitted to the clinic of surgery for surgical treatment of bleeding gastric ulceration. Preoperative diagnostic evaluation was performed, and patient had undergone a surgical treatment which revealed a large mass in head of the pancreas, infiltrating the hepatoduodenal ligament and transverse mesocolon. Total gastrectomy, duodenopancreatectomy, and right hemicolectomy were performed. The digestive tube continuity was reestablished by deriving the double Roux limbs. Conclusion. The aim of this case presentation is to demonstrate a method of digestive tube reconstruction by performing the double Roux-en-Y reconstruction in advanced gastric cancer when the multivisceral resection is performed.

Intramural Haemorrhage and Haematoma as the Cause of Ileus of the Small Intestine in a Haemophiliac.

INTRODUCTION: The most frequent sites of bleeding in patients with haemophilia are the soft tissues, the joints, the urinary tract, but much more rarely the gastrointestinal tract. The complications of intramural bleeding are acute intestinal obstruction, but also rupture of the haematoma in the lumen or the peritoneal space. CASE REPORT: We present the case of a haemophiliac patient who was admitted as an emergency due to distended abdomen, nausea, vomiting and the clinical picture of ileus. The native abdomen in a standing position presented air fluid levels with moderate distension of the accompanying bowel loops. A nasal probe was inserted and the symptoms of ileus disappeared, but after taking food by mouth, the picture of ileus returned. CT of the abdomen and pelvis was performed, which showed circular, high density thickening of the walls in places in the area of the jejunum, indicating haemorrhage, but also the formation of haematoma in the wall structure. After administering factor VIII, the symptoms of ileus ceased, and the patient recovered completely. CONCLUSION: This unusual presentation of haemophilia with bleeding in the wall of the small intestine is very rare and has only been seen in a few cases in the world. CT diagnosis defined the cause of the obstruction and saved the patient from an unnecessary surgical procedure.

Regulation of DNA replication at the end of the mitochondrial D-loop involves the helicase TWINKLE and a conserved sequence element.

The majority of mitochondrial DNA replication events are terminated prematurely. The nascent DNA remains stably associated with the template, forming a triple-stranded displacement loop (D-loop) structure. However, the function of the D-loop region of the mitochondrial genome remains poorly understood. Using a comparative genomics approach we here identify two closely related 15 nt sequence motifs of the D-loop, strongly conserved among vertebrates. One motif is at the D-loop 5'-end and is part of the conserved sequence block 1 (CSB1). The other motif, here denoted coreTAS, is at the D-loop 3'-end. Both these sequences may prevent transcription across the D-loop region, since light and heavy strand transcription is terminated at CSB1 and coreTAS, respectively. Interestingly, the replication of the nascent D-loop strand, occurring in a direction opposite to that of heavy strand transcription, is also terminated at coreTAS, suggesting that coreTAS is involved in termination of both transcription and replication. Finally, we demonstrate that the loading of the helicase TWINKLE at coreTAS is reversible, implying that this site is a crucial component of a switch between D-loop formation and full-length mitochondrial DNA replication.

A rare case of biliary leakage after laparoscopic cholecystectomy-diagnostic evaluation and nonsurgical treatment: a case report.

Although laparoscopic cholecystectomy has become a gold standard in treatment of symptomatic cholelithiasis, it is associated with higher risk of intraoperative lesions and primarily lesions of biliary ducts. In small percentage of cases biliary fistulas occur, most commonly after leakage from cystic duct stump or accessory bile ducts - Luschka's duct. We report of a patient who had episodes of abdominal pain following routine laparoscopic cholecystectomy for acute calculous gallbladder. Results of conducted diagnostics verify the presence of biliary fistula caused by obstruction of bile pathways by stagnant pus and microcalculi of common bile duct, with development of biloma presumably caused by pressure injection of contrast material during ERCP procedure. Endoscopic sphincterectomy via ERCP enabled healing of formed biliary fistula, whilst continuous percutaneous ultrasound guided drainage of biloma was method of choice in later treatment of our patient. It is important to note that diagnostic evaluation of biliary fistula is very challenging and that timely nonsurgical treatment is of great benefit for patient.

In vitro-reconstituted nucleoids can block mitochondrial DNA replication and transcription.

The mechanisms regulating the number of active copies of mtDNA are still unclear. A mammalian cell typically contains 1,000-10,000 copies of mtDNA, which are packaged into nucleoprotein complexes termed nucleoids. The main protein component of these structures is mitochondrial transcription factor A (TFAM). Here, we reconstitute nucleoid-like particles in vitro and demonstrate that small changes in TFAM levels dramatically impact the fraction of DNA molecules available for transcription and DNA replication. Compaction by TFAM is highly cooperative, and at physiological ratios of TFAM to DNA, there are large variations in compaction, from fully compacted nucleoids to naked DNA. In compacted nucleoids, TFAM forms stable protein filaments on DNA that block melting and prevent progression of the replication and transcription machineries. Based on our observations, we suggest that small variations in the TFAM-to-mtDNA ratio may be used to regulate mitochondrial gene transcription and DNA replication.