Search Results (56)

Down syndrome (DS), caused by trisomy 21, is associated with a wide spectrum of endocrine and gastrointestinal disorders that often arise early in life and significantly impact long-term health. This narrative review examines the pathophysiological mechanisms underlying these conditions, with a particular focus on their bidirectional interactions. Endocrine abnormalities in DS, including thyroid dysfunction, type 1 diabetes mellitus, growth impairment, and altered bone metabolism, occur at higher rates than in the general population and are largely driven by immune dysregulation, chronic inflammation, and gene dosage effects. Similarly, gastrointestinal disorders—ranging from congenital malformations to autoimmune conditions such as celiac disease—are highly prevalent and often present with atypical clinical features. Emerging evidence highlights the central role of gut dysbiosis, characterized by reduced microbial diversity and increased pro-inflammatory taxa, in modulating immune and metabolic pathways. This altered gut environment contributes to a chronic inflammatory state and may promote autoimmunity and endocrine dysfunction through the gut–endocrine–immune axis. Nutritional deficiencies and epigenetic factors, including microRNA dysregulation, further influence disease expression. Understanding this complex cross-talk is essential for improving clinical management. Integrated, multidisciplinary approaches and early screening strategies are crucial to optimize outcomes and guide future research in DS. Full article

Background/Objectives: Congenital gastrointestinal malformations (CGIMs) are important causes of neonatal surgical morbidity with potential long-term consequences. Although some can be suspected on prenatal ultrasound, data on their clinical spectrum, burden, and distribution remain limited in Eastern Europe. This study aimed to describe the diagnostic spectrum, timing of diagnosis, documented prenatal ultrasound suspicion, and the early outcomes of CGIMs managed at a Romanian tertiary referral centre between 2020 and 2024, a period overlapping the COVID-19 pandemic. Methods: We conducted a retrospective, single-centre observational study including all consecutive paediatric patients with a CGIM admitted between January 2020 and December 2024. Cases were analysed by index anatomical diagnosis, phenotypic complexity, and etiologic background. Logistic regression was used to examine factors associated with documented prenatal suspicion and in-hospital mortality, and annual hospital-based CGIM admission rates were modelled with Poisson regression, using the number of paediatric surgical admission as the offset. Results: Among the 231 children (58.9% male), the most frequent diagnoses were persistent omphalomesenteric duct remnants (16%), oesophageal atresia with or without tracheoesophageal fistula (15.6%), and anorectal malformations (13.9%). Documented prenatal ultrasound suspicion was present in 17.7% of pregnancies (41/231) and was likely underestimated because antenatal documentation was unavailable for 17.7% of the cohort. The highest proportions of documented prenatal suspicion were observed in jejuno-ileal and duodenal atresia. Foregut malformations were the most common by embryological grouping (93/231, 40.3%). Most cases were diagnosed during the neonatal period (n = 161, 69.7%). CGIM admission rates per 1000 surgical admissions ranged from 20.8 to 38.2. An exploratory Poisson model yielded a hospital-based rate ratio per calendar year of 0.88 (95% CI 0.81–0.97; p = 0.008). However, given the limited number of annual observations and increasing total surgical admissions, this finding should be considered exploratory and hypothesis-generating only. Complex cases accounted for 8.2% and associated extra-intestinal anomalies were present in 70.1%. In-hospital mortality was 13.0% and occurred predominantly in patients with complex or foregut malformations. In the primary complete-case multivariable model, prematurity remained independently associated with mortality, whereas complex CGIMs were not independently associated with mortality after adjustment. A prespecified multiple-imputation sensitivity analysis yielded a stronger estimate for complex CGIMs, but this finding was interpreted cautiously and not treated as a primary result. Conclusions: In this tertiary referral cohort, documented prenatal suspicion of CGIM was low and strongly diagnosis-dependent, while most cases were identified in the neonatal period. Mortality was concentrated in foregut and clinically complex presentations in the descriptive analysis, while prematurity remained independently associated with death in the primary multivariable model. These findings highlight the need to strengthen prenatal referral pathways and coordinated national surveillance. Full article

Objective. Limited evidence is available concerning the surgical outcomes of patients with congenital gastrointestinal malformations and perioperative SARS-CoV-2 infection. This study examines the scientific evidence on SARS-CoV-2 infection and congenital gastrointestinal malformations requiring surgery in children. Material and Methods. We performed a systematic review of studies reporting data on children with congenital gastrointestinal malformations and SARS-CoV-2 infection, published in international databases (PubMed and Embase) from pandemic inception up to August 2024. Studies not reporting data on the SARS-CoV-2 infection status on patients with congenital digestive malformation were excluded. We assessed the quality of the included studies according to the Joanna Institute (JBI) appraisal checklist, adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, and registered the protocol with the PROSPERO database (CRD42024550744). Results. From the 902 titles retrieved, eight observational studies met the inclusion criteria comprising 29 patients from countries with different socioeconomic statuses. Most patients were neonates (75%) with a median age of 3 days at diagnosis and male to female ratio of 2:1. In total, 18 (62%) presented upper gastrointestinal tract anomalies, including esophageal atresia ± tracheoesophageal fistula (n = 10, 34.48%), duodenal atresia (n = 3, 10.3%), and congenital hypertrophic pyloric stenosis (n = 5, 17.2%). Lower digestive tract malformations (11, 38%) included anorectal malformations (n = 6, 20.6%), intestinal atresia (n = 3, 10.3%), Hirschsprung disease (n = 1, 3.44%), and Meckel’s diverticulum (n = 1, 3.44%). Surgeries were primarily emergency or urgent procedures and only pyloromyotomy (5/5) was consistently operated minimally invasively. SARS-CoV-2 infection was identified mainly on routine screening (>95%). Of 29 patients, 85% were discharged home, and no postoperative surgical mortality and significant complications directly associated with COVID-19 were identified, although routine postoperative morbidity not linked to SARS-CoV-2 was observed. Conclusions. Pediatric patients with congenital gastrointestinal malformationsand perioperative SARS-CoV-2 infection typically have mild illness and favorable surgical outcomes. SARS-CoV-2 positivity alone should not delay essential surgery when infection control measures are ensured. Standardized, multicenter studies are needed to clarify perioperative risks to and inform management of this high-risk group. Full article

Background: Hereditary hemorrhagic telangiectasia (HHT) is an inherited vascular bleeding disorder. The most common symptoms are recurrent, severe nosebleeds that occasionally necessitate intervention by an ENT (Ear, Nose, and Throat) specialist, as well as iron-deficiency anemia. Telangiectasia is typically located in the nasal cavity, lips, tongue, fingertips, and the gastrointestinal mucosa. Arteriovenous malformations (AVMs) are located in internal organs (brain, lungs, liver, etc.). The family history is positive for HHT. The diagnosis is based on the Curacao criteria. The endoglin and activin receptor-like kinase 1 genes (ENG and ACVRL1) are the most common mutation sites, leading to elevated endothelial growth factor (VEGF) levels. Methods: We conducted a retrospective analysis in the Department of Internal Medicine, Division of Hematology, and Center of Expertise for Rare Diseases at the University of Debrecen, spanning the period from 2010 to 2025. Records of patients referred with HHT were reviewed concerning demographic data, clinical presentations, laboratory findings, and treatment approaches. To evaluate management options, epistaxis severity was assessed using the Epistaxis Severity Score (ESS). Results: 48 HHT patients (21 male and 27 female) were included in this retrospective study. Genetic testing was positive in each case, showing mutations in the ENG (HHT1 subgroup) or ACVRL1 (HHT2 subgroup) genes. Most of the patients are followed-up with in our department. ESS was calculated at baseline and 6 months after antiangiogenic treatment by two independent physicians. Detailed computed tomography (CT) was performed in all patients. Seven patients were administered desmopressin, a synthetic analog of antidiuretic hormone (ADH), based on our previous experience in reducing bleeding in von Willebrand disease. Antiangiogenic therapy with thalidomide (50 mg oral tablets) was used in 24 patients, while bevacizumab was administered to 5 patients. Most patients experienced a remarkable decrease in epistaxis severity and a reduction in the need for transfusions (ESS before treatment: HHT1 patients, 4.15 ± 1.91 vs. ESS after treatment, 2.62 ± 0.99; HHT2 patients, 3.79 ± 3.19 vs. 2.02 ± 1.91). Subgroup analysis using paired ESS data showed a significant reduction in ESS in both HHT1 and HHT2 patients (p = 0.003 and p = 0.043, respectively). Bevacizumab further reduced the ESS, but the few cases were not suitable for statistical analysis. Serum iron levels significantly increased after antiangiogenic treatment in the HHT2 group (p = 0.01). Conclusions: HHT is a rare vascular bleeding disorder. Daily nosebleeds impair the patients’ quality of life and sometimes lead to severe transfusion-dependent iron-deficient anemia. Frequent hospitalization places a significant burden on the healthcare system. Thus, we have used treatment options for HHT patients that primarily act by inhibiting VEGF, and these treatment modalities have yielded successful results in our hands. Full article

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler–Weber–Rendu disease, is an autosomal dominant vascular disorder caused most commonly by pathogenic variants in the ENG and ACVRL1/ALK1 genes. It is characterized by mucocutaneous telangiectasias and arteriovenous malformations (AVMs) in various organs, leading to recurrent epistaxis, gastrointestinal bleeding, and iron deficiency anemia. Diagnosis relies on the Curaçao Criteria, which include recurrent nosebleeds, characteristic telangiectasias, visceral AVMs, and family history. This review aims to present current therapeutic approaches and emerging treatment strategies for HHT. Traditional surgical and laser-based methods are increasingly complemented or replaced by targeted pharmacological interventions. Antiangiogenic agents such as bevacizumab and thalidomide have demonstrated efficacy in reducing bleeding frequency and transfusion requirements, although adverse effects may limit long-term use. Novel therapies under investigation target molecular pathways involved in vascular remodeling, including tyrosine kinase inhibitors (sorafenib, nintedanib), anti-ANGPT2 antibodies, and modulators of BMP9/ALK1 signaling (tacrolimus, sirolimus). Preclinical and early clinical studies suggest that these agents may provide disease-modifying benefits. Continued research should focus on optimizing treatment efficacy, reducing toxicity, and developing individualized therapeutic regimens based on genetic and clinical characteristics. Full article

Background and Clinical Significance: Extremely premature infants face complex medical challenges requiring comprehensive multidisciplinary care. Gastrointestinal malformations, while rare, pose significant diagnostic and therapeutic challenges in this vulnerable population. Case Presentation: We report a case of an extremely premature infant born at 26 weeks gestation with very low birth weight (950 g) who developed a digestive pathology rarely encountered in neonatal intensive care: microcolon, which required surgical consultation and intervention, followed by an atypical postoperative course. Conclusions: The early recognition of gastrointestinal malformations in extremely premature infants requires high clinical suspicion and prompt multidisciplinary intervention. Despite complex postoperative course, favorable outcomes are achievable with coordinated care. Full article

Background: Congenital gastrointestinal anomalies (CGIAs) are the third most common congenital malformation globally, with a mortality rate reaching 39.8% in developing countries. Surgical intervention is often necessary for life-saving or corrective purposes. However, postoperative mortality in resource-limited settings can reach up to 50%. Identifying prognostic factors is essential to improve clinical management and inform family counseling regarding potential outcomes. Objectives: We aimed to develop a prognostic scoring system to predict postoperative mortality in neonates with CGIAs. Methods: This retrospective study analyzed medical records of neonates who underwent surgery for CGIAs between 2020 and 2024. Prognostic factors were identified using logistic regression analysis. Receiver operating characteristic (ROC) curves were used to determine optimal cutoff points for mortality prediction. Results: A total of 282 neonates were included; 121 (42.9%) died and 161 (57.1%) survived. Multivariate logistic regression identified sepsis, mechanical ventilation, prematurity, and upper gastrointestinal anomalies as independent predictors of mortality. A scoring system was developed, with a score > 3 yielding a sensitivity of 83.5% and specificity of 72.0%. The area under the ROC curve (AUC) was 0.840 (p < 0.001). Conclusions: We developed a simple and reliable scoring system to predict postoperative mortality in neonates with CGIAs, which may support clinical decision-making and family counseling. Full article

Background: Unilateral lung agenesis (ULA) is a rare congenital anomaly characterized by the complete absence of one lung, often accompanied by cardiovascular, skeletal, or gastrointestinal malformations. Despite its clinical significance, evidence of prevalence, anatomical variants, and outcomes remain fragmented. This systematic review aimed to synthesize existing data on ULA’s prevalence, anatomical classifications, diagnostic approaches, and clinical implications. Methods: Following PRISMA 2020 guidelines, five databases (MEDLINE, Web of Science, CINAHL, Scopus, and EMBASE) were searched from inception to January 2024. Inclusion criteria encompassed case reports, case series, and observational studies on ULA in humans. Risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist. Narrative synthesis was performed due to methodological heterogeneity. Results: Thirty-two studies (137 participants) were included. Right-sided ULA predominated (58%), with poorer prognoses due to mediastinal distortion. Cardiovascular anomalies (40%) were the most common comorbidity. Diagnostic modalities included chest radiography (85%), CT (70%), and bronchoscopy (25%). Schneider-Boyden scale was used to classify the included studies. Risk of bias assessment revealed 65% of studies as low risk, 28% as moderate, and 7% as high risk. Conclusions: ULA necessitates multidisciplinary management, particularly in cases with associated anomalies. Left-sided ULA correlates with better outcomes, emphasizing the role of early imaging. Limitations include reliance on case reports and inconsistent reporting of anatomical variants. Future research should adopt standardized classifications and longitudinal designs to improve evidence quality. Open science framework (OSF): 10.17605/OSF.IO/XVQSP. Full article

Background: The population affected by gastrointestinal atresias and neurodevelopmental outcomes has not been well studied. Current evidence suggests that damage to the central nervous system is important in congenital gastrointestinal malformations. This study aims to understand the effects of gastrointestinal atresias on neurodevelopmental outcomes in our patient group. Methods: This cross-sectional, population-based study examined patients with congenital gastrointestinal atresias who were admitted to the neonatal intensive care unit and underwent gastrointestinal surgery. The Bayley III scale was administered to 32 patients aged 7–42 months. Results: Thirty-two patients with gastrointestinal atresia were included in the study. Eighteen (56.2%) of the patients were male. The median gestational age was 37 weeks (range 25–39 weeks) and the median birthweight was 2700 g (range 700–3800 g). A Bayley III evaluation was performed at a median age of 13.7 months (range 7–41 months). The cognitive, motor, and language composite scores were 90, 86, and 89, respectively. The motor score was lower than the cognitive and language scores. No statistical difference was found between low scores, gender and stoma presence in all three neurodevelopmental categories (p < 0.05). Conclusion: Patients with congenital gastrointestinal malformations are reported in the literature to have lower motor and language development scores. In our study, lower cognitive and language scores were observed in only one patient, whereas motor delay was more prevalent in the study population. The close neurodevelopmental follow-up of infants with gastrointestinal atresies may improve the quality of life. Full article

Background/Objectives: Rendu–Osler disease is a rare genetic disease, characterized by widespread telangiectasia that can involve the skin and mucous membranes. The diagnosis is based on spontaneous and recurrent epistaxis; various mucosal and cutaneous telangiectasia at typical sites; visceral manifestations including gastrointestinal telangiectasia or pulmonary, cerebral, or hepatic arteriovenous malformation; and a first-degree relative with hereditary hemorrhagic telangiectasia. Squamous cell carcinoma of the larynx generally develops in patients with a smoking history. It is most often treated by surgery and/or radiotherapy. To our knowledge, these two entities were never reported in the same patient. Methods: We herein report a case of a 51-year-old man with Rendu–Osler disease. He was subsequently diagnosed with a locally advanced well-differentiated squamous cell carcinoma of the vocal cord. Results: The patient received a neo-adjuvant chemo-immunotherapy, with nine weekly injections of paclitaxel (60 mg/m²/week), cisplatin (30 mg/m²/week), and cetuximab (250 mg/m²/week), and three injections of pembrolizumab (200 mg every 3 weeks). This controlled tumor bleeding, and then cisplatin-enhanced radiotherapy helped obtain a complete remission. Conclusions: Locally advanced squamous cell carcinoma of the larynx treatment in the context of active Rendu–Osler disease is challenging. If the wide curative surgical approach is deemed too risky, neo-adjuvant chemo-immunotherapy may present a helpful alternative as it may enhance the conditions in order to perform classical radiotherapy with concomitant cisplatin. Full article

Aorto-esophageal fistula (AEF) is a condition with an extremely high mortality rate that often causes massive gastrointestinal bleeding, commonly resulting from esophageal perforation due to foreign bodies or aortic aneurysmal malformations. This case report introduces an elderly male patient who experienced hematemesis for longer than 16 h without obvious cause. The patient did not receive relief from endoscopic compression hemostasis. Through computed tomography angiography (CTA), a tortuous and thickened vessel was found in the descending aorta of the patient, which entered the esophagus. The diagnosis was AEF caused by vascular malformation. which has not been previously documented in the literature. Full article

Background/Objectives: Turner syndrome (TS) is a genetic chromosomal disorder including various manifestations depending on the karyotype; endocrine, gastrointestinal, respiratory, neurological, urogenital, musculoskeletal, and cardiovascular disorders contribute to increased morbidity and mortality. Liver function abnormalities are less well studied and mostly associated with insulin resistance, obesity, diabetes, hypogonadism, hypothyroidism, and autoimmune conditions. The association of liver pathology with architectural changes in various etiologies and the metabolic dysfunction-associated liver disease is of particular interest. Methods: Herein, we present three cases of adult women with TS and the persistent elevation of liver enzymes due to porto-sinusoidal vascular disorder (PSVD). Results: In one case, the diagnosis of TS followed the liver biopsy results. The absence of cardiometabolic risk factors, low liver stiffness and cardiovascular malformations may predict this histological diagnosis. Conclusions: Liver function impairment in TS may derive from a broad spectrum of liver pathology, including PSVD, and requires careful evaluation to decrease the risk of complications. Full article

Background and Clinical Significance: Gastrointestinal bleeding is a critical medical emergency, with upper gastrointestinal bleeding occurring approximately five times more frequently than lower gastrointestinal bleeding (LGIB). The incidence of LGIB tends to increase with age, likely due to a greater prevalence of vascular and diverticular diseases among older patients. However, there are rare or extremely rare causes of LGIB that demand significant diagnostic and therapeutic efforts, some of which may pose unexpected challenges during surgery. Case report: We present the case of a 75-year-old woman, previously treated for a cecal neoplasm 15 years ago, who was hospitalized due to intermittent lower gastrointestinal bleeding over the past three months. Initially, the patient declined a colonoscopic examination, and the bleeding stopped spontaneously. She was then discharged at her own request in stable condition. However, she returned with a recurrence of the bleeding. While preparing for a colonoscopy, she experienced subocclusive symptoms, abdominal distension, and vomiting. During emergency surgery, a floating coprolith, which was attached to one of the anastomosis sutures, was sensed through palpation and later confirmed via colotomy. The coprolith was removed, and hemostasis was achieved in situ, leading to a favorable postoperative recovery and normalization of intestinal transit. A literature review identified 24 articles that met the eligibility criteria concerning rare causes of LGIB. Appendiceal bleeding (due to erosions, arteriovenous malformations, or endometriosis) was the most common cause, whereas the rarest causes included jejunal hemangiomas and rectal ulcers resulting from mucormycosis. Diagnosing these conditions is often challenging, typically requiring CT scans, colonoscopy, and angiography, with surgical treatment being the primary method to ensure hemostasis. In conclusion, the diagnosis and management of LGIB present significant challenges for clinicians, and successful outcomes are usually achieved through a collaborative multidisciplinary team approach. Full article

Background: The umbilical cord normally contains two arteries and one vein. The presence of supernumerary—four or five—umbilical cord vessels is a rare phenomenon, with few cases reported in the literature. The majority of cases are detected postnatally. However, given their potential association with developmental abnormalities, primarily severe cardiac anomalies and genetic disorders, the prenatal diagnosis of supernumerary umbilical cord vessels may have clinical relevance. Methods: A review of the clinical phenomenon of the four-vessel umbilical cord and its complications was conducted using case studies and literature reviews in PubMed from 1977 to the present and in Google Scholar from 1966 to the present. Results: Among the 24 reported cases, 7 cases were associated with malformations, 8 cases were detected antenatally, and 16 cases postpartum. Among the eight antenatally diagnosed cases, only one had a congenital malformation, hydrops fetalis. Among the postnatally diagnosed cases, six had congenital abnormalities: three were cardiovascular, two were associated with hydrops, urinary, gastrointestinal, and skeletal disorders, hypoplastic corpus callosum, and dysmorphic facial features. Conclusions: Four-vessel umbilical cords are more frequent than previously thought, as they can be easily overlooked during the mandatory ultrasound examination. A review of the literature revealed a correlation between supernumerary umbilical cord vessels and major congenital malformations, underscoring the significance of prenatal diagnosis; however, the four-vessel cord may not always be indicative of a serious condition. Full article

Mowat–Wilson syndrome (MWS) is a rare multi-system genetic disorder caused by variants in the Zinc Finger E-Box-Binding Homeobox 2 (ZEB2) gene. ZEB2 is an autosomal dominant gene containing ten exons within the canonical version transcript (Isoform: O60315-1). The ZEB2 gene encodes six functional domains and seven non-domain regions. This review provides a comprehensive summary of pathogenic variants and their associated MWS clinical characteristics, focusing on ZEB2 pathogenic variants, functional protein domains and non-domain regions with clinical features. A systematic literature search from 2001 to 2023 and of unpublished datasets found 191 individuals with reported clinical features and genotypic data. Genetic defects and clinical manifestations were examined that presumably impact on the structure and function of the ZEB2 gene, thereby causing multiple developmental defects with corresponding clinical presentation. This study found more nonsense ZEB2 variants observed within exon 8, which encodes four of the six protein domains: the CtBP-interacting domain (CID), homeodomain (HD), SMAD-binding domain (SMD or SBD) and part of the N-terminal zinc finger cluster (N-ZF), suggesting exon 8 plays a crucial role in this protein structure and function with multi-organ involvement. Exon 8 defects were found to be statistically more represented for gastrointestinal findings when compared to other exons, while frameshift defects were more often seen for the typical MWS face in non-domain protein regions. In contrast, nonsense or other types of variants in exons 3, 4 and 5 which encode only flanking non-domain regions were observed more often, compared with other exons excluding exon 8, to be specifically involved in the MWS facial gestalt, brain malformations, developmental delay and intellectual disability. Deleterious ZEB2 frameshift (45%) and nonsense (38%) gene variants were most often observed with deletions at 6% and missense at 5%. The genotype and clinical relationships in MWS can provide insights into prognosis, morbidity, clinical surveillance strategies and counseling of family members. Full article