Managing severe warm autoimmune haemolytic anaemia after the SARS-Cov- 2 vaccine with emergency splenectomy and eculizumab

Autoimmune haemolytic anaemia (AIHA) is rare but described after the SARS-CoV- 2 Pfizer-BioNTech vaccine. We present a case of severe refractory warm AIHA after this vaccine, managed with emergency splenectomy and complement inhibition with eculizumab. A male in his teens with a history of liver transplant for biliary atresia (aged 2 years) and AIHA (aged 6 years) presented to his district general hospital with jaundice, dark urine, fatigue and chest discomfort 48 h after the first dose of SARS-CoV- 2 Pfizer-BioNTech vaccine (BNT162b2 mRNA). Investigations revealed haemoglobin (Hb) of 70 g/L and bilirubin of 98 mumol/L, which was treated as AIHA. The patient initially responded to prednisolone (1 mg/kg, 60 mg) but subsequently deteriorated and failed to respond to second-line rituximab (375 mg/m2) and two units of packed red blood cells (PRBC). By day 29 the patient had developed life-threatening anaemia culminating in a Hb of 35 g/L (after transfusion), lactate dehydrogenase (LD) of 1293 units/L and bilirubin of 228 mumol/L. This necessitated an immediate transfer to our tertiary centre for specialist support. Further investigations revealed a haptoglobin <0.1 g/L and direct antiglobulin test (DAT) strongly positive for IgG (4+) and negative for C3d. The peripheral blood film showed severe anaemia, nucleated red cells, anisocytosis and spherocytes with no autoagglutination, schistocytes or platelet clumps. Thrombocytopaenia (platelets 49 +/- 109/L) was present. Differentials were ruled out, such as paroxysmal nocturnal haemoglobinuria and heparin-induced thrombocytopaenia. HIV and hepatitis serology were negative, as were adenovirus, cytomegalovirus and Epstein-Barr virus PCR assays. A CT showed splenomegaly of 15.5 cm. Urinalysis found urobilinogen and bilirubin at high concentrations and negative urinary haemosiderin. Together, the investigations were consistent with warm AIHA. On day 29, four units of PRBC were transfused alongside 100 mg methylprednisolone and 1 g/kg IVIG. On day 30 the patient deteriorated despite the escalated treatment: Hb had only increased to 54 g/L, bilirubin was 200 mumol/L and LD was rising. Considering this life-threatening fulminant haemolysis, an emergency splenectomy was performed. This slowed haemolysis but did not completely ameliorate it: by day 33 the patient had received 15 units of PRBC. Thus, eculizumab, a terminal complement pathway inhibitor, was trialled to arrest intravascular haemolysis, alongside rituximab, repeat IVIG 1 g/kg, prednisolone 40 mg and tacrolimus 2 mg. This showed a favourable response, requiring less frequent transfusions and settling haemolysis. This case highlights the rare complication of warm AIHA with the SARS-CoV- 2 Pfizer-BioNTech vaccine, the use of emergency splenectomy for disease control, and the potential of eculizumab for refractory cases.

A baby girl with TBX1 haploinsufficiency who died after elective cardiac repair surgery due to suspected enteroviral meningitis

Introduction: TBX1 haploinsufficiency is an inborn error of immunity with the phenotype of DiGeorge Syndrome. DiGeorge Syndrome has variable immunodeficiency associated with grade of thymic hypoplasia ranging from mild with no infections to severe requiring thymus implant. Enterovirus is an example of an opportunistic infection that can be fatal in these patients. Case Presentation: A 1 year old girl with TBX1 haploinsufficiency complicated by Tetralogy of Fallot, pulmonary atresia, high arched palate, and vesicovaginal fistula presented for elective cardiac repair surgery from another country due to failure to thrive and cyanosis. She had no prior infectious history but was on sulfamethoxazole-trimethoprim for prophylaxis. She was asymptomatic with a negative COVID test but no other infectious studies performed. Immediately postoperatively, she was febrile and nasal respiratory viral panel was positive for rhinovirus/enterovirus with increased procalcitonin and leukocytosis with left shift. She decompensated with multi-organ failure and cardiac arrest on postoperative day two. She was cannulated to veno-arterial extracorporeal membrane oxygenation (ECMO). Pre-operatively, she had a normal absolute lymphocyte count. No thymus tissue was observed in surgery. She had profound CD3 lymphopenia to 130 cells/cmm when critically ill. Enteroviral meningitis was suspected as no infectious, cardiac, or other pathology could be identified causing decompensation. Enteroviral serum polymerase chain reaction (PCR) test was negative while lumbar puncture deferred due to clinical status. She was treated with immunoglobulin. Offlabel investigational drug pocapavir was considered but deferred to patient's irreversible neurological status. The patient was disconnected from ECMO and expired. Discussion(s): Though we cannot confirm that this patient had enteroviral meningitis, invasive enteroviral infections are associated with elevated transaminases, coagulopathy, and seizures all present in our patient. There has also been reported negative serum enteroviral PCR but positive CSF enteroviral PCR in an immunodeficient patient. Additionally, this case highlights the importance of immunologic evaluation in patients with DiGeorge Syndrome and questions if asymptomatic viral screening for viruses like enterovirus should be considered pre-operatively in patients with inborn errors of immunity. This case highlights potential treatment options for invasive enteroviral infections in patients with inborn errors of immunity: high dose immunoglobulin, fluoxetine, and pocapavir.Copyright © 2023 Elsevier Inc.

Jahrestagung der Gesellschaft fur Padiatrische Pneumologie.

The proceedings contain 54 papers. The topics discussed include: cytokines in severe childhood asthma;transcriptional gene regulation of interleukin-6 in epithelial cells in viral-induced asthma exacerbation;assessment of the long-term safety and efficacy of dupilumab in children with asthma: LIBERTY ASTHMA EXCURSION;impulse oscillometry bronchodilator response in preschool children;pulmonary function in non-hospitalized adults and children after mild Covid-19;exhaled aerosols in PCR-confirmed SARS-CoV-2-infected children;early respiratory infectious diseases have an influence on the gut microbiome;comparison of three eradication treatment protocols for pseudomonas aeruginosa in children and adolescents with cystic fibrosis;neutrophilic airway inflammation in children with repaired esophageal atresia-tracheoesophageal fistula (EA/TEF);and multiplex immunofluorescence and multispectral imaging as a tool to evaluate host directed therapy.

Incidence of congenital complications related to COVID-19 infection during pregnancy.

PURPOSE: Infection with COVID-19 during pregnancy has been associated with a hypercoagulable state. It is unknown if maternal COVID-19 infection results in congenital anomalies secondary to intrauterine vascular accidents. This study sought to determine if the rate of in-utero vascular complications (intestinal atresia and limb abnormalities) that may be attributable to the hypercoagulable states associated with COVID-19 and pregnancy increased after the onset of the pandemic. METHODS: Pregnancy, neonatal, and congenital defect data from a single academic medical center and the partner's children's hospital were collected and compared to the period prior to onset of the pandemic. A subanalysis including pregnant woman 18 years or greater with documented COVID-19 infection during gestation between March 2020-2021 was performed. RESULTS: Rates of intestinal atresia did not differ prior to or after the onset of the pandemic (3.78% vs 7.23%, p = 0.21) nor did rates of limb deficiency disorders (4.41% vs 9.65%, p = 0.09). On subanalysis, there were 194 women with COVID-19 infection included in analysis: 135 (69.6%) were positive during delivery admission and 59 (30.4%) were positive earlier in their pregnancy. There was one infant born with intestinal atresia. CONCLUSION: We report a low incidence of congenital anomalies in infants born to mothers with COVID-19 infection. It remains unclear if the impact of COVID-19 on the coagulative state augments the normal pro-thrombotic state of pregnancy; ongoing surveillance is warranted.

Special considerations in the premature and ex-premature infant

Advances in neonatal medicine have progressively increased the survival of premature infants. Increased survival has however come at the cost of increased number of infants with prematurity-related complications. This is represented by high rates of respiratory distress syndrome, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), sepsis, periventricular leukomalacia (PVL), intraventricular haemorrhage (IVH), cerebral palsy, hypoxic ischaemic encephalopathy (HIE) and visual and hearing problems in survivors. In addition to prolonged hospital stay after birth, readmission to hospital in the first year of life is common if chronic lung disease exists. Around 3% of newborns have a congenital physical anomaly with 60% of congenital anomalies affecting the brain or heart and around 1% having multiple anomalies. Individual congenital conditions requiring surgical intervention in the neonatal period are rare. Neonates have a higher perioperative mortality risk largely due to the degree of prior illness, the complexity of their surgeries, and infant physiology. The maintenance of oxygenation and perfusion in the perioperative phase is critical as both affect cerebral perfusion and neurocognitive outcome but the triggers for intervention and the thresholds of physiological parameters during neonatal anaesthesia are not well described. After even minor surgical procedures, ex-premature infants are at higher risk for postoperative complications than infants born at term.Copyright © 2022

The Prevalence of COVID-19 in Asymptomatic Cases and Its Effect on Complication Development in Children Scheduled for Emergency and Urgent Surgery.

Objective: Although COVID-19 in childhood is often asymptomatic or has a more benign course, the safety of healthcare workers should be the primary goal because of the risk of contamination. In our study, we aimed to investigate the asymptomatic COVID-19 PCR positivity and its effect on the development of complications in emergency and non-deferred surgery cases that will help both the patient, the operating room and the health care workers. Material(s) and Method(s): This is a prospective study that was performed in patients under 18 years of age who were operated on due to emergency and urgent cases in the Ankara City Children's Hospital, which was serving as an anti-pandemic hospital. The patients were evaluated from May 1 to October 1, 2020. Of the 458 patients, 433 patients who met the criteria were included in the study. COVID-19 Nasopharyngeal swab (PCR) samples were taken from all patients along with preoperative examinations. Result(s): Of the 433 cases included in the study, 155 (33.5%) were girls and 278 (66.5%) were boys. It was determined that emergency cases constituted 389 (89.8%) of all cases. The most common emergency pathologies according to age groups were intestinal obstruction or atresia in the neonatal period, foreign body aspirations of the respiratory tract in the preschool period, and acute appendicitis in the school age. Nasal swab PCR results were positive in only four patients, this rate was found to be 0.9% in the entire study group, and postoperative complications and transmission to healthcare workers were detected at none. Conclusion(s): In this prospective study, low COVID-19 PCR positivity (0.9% prevalence) was detected in asymptomatic children scheduled for emergency or non-deferred surgery, and we believe that it will shed light on the planning of safe procedure practices.Copyright © 2021 Ankara Pediatric Hematology Oncology Training and Research Hospital. All rights reserved.

The Prevalence of COVID-19 in Asymptomatic Cases and Its Effect on Complication Development in Children Scheduled for Emergency and Urgent Surgery

Objective: Although COVID-19 in childhood is often asymptomatic or has a more benign course, the safety of healthcare workers should be the primary goal because of the risk of contamination. In our study, we aimed to investigate the asymptomatic COVID-19 PCR positivity and its effect on the development of complications in emergency and non-deferred surgery cases that will help both the patient, the operating room and the health care workers. Material and Methods: This is a prospective study that was performed in patients under 18 years of age who were operated on due to emergency and urgent cases in the Ankara City Children's Hospital, which was serving as an anti-pandemic hospital. The patients were evaluated from May 1 to October 1, 2020. Of the 458 patients, 433 patients who met the criteria were included in the study. COVID-19 Nasopharyngeal swab (PCR) samples were taken from all patients along with preoperative examinations. Results: Of the 433 cases included in the study, 155 (33.5%) were girls and 278 (66.5%) were boys. It was determined that emergency cases constituted 389 (89.8%) of all cases. The most common emergency pathologies according to age groups were intestinal obstruction or atresia in the neonatal period, foreign body aspirations of the respiratory tract in the preschool period, and acute appendicitis in the school age. Nasal swab PCR results were positive in only four patients, this rate was found to be 0.9% in the entire study group, and postoperative complications and transmission to healthcare workers were detected at none. Conclusion: In this prospective study, low COVID-19 PCR positivity (0.9% prevalence) was detected in asymptomatic children scheduled for emergency or non-deferred surgery, and we believe that it will shed light on the planning of safe procedure practices.

The Prevalence of COVID-19 in Asymptomatic Cases and Its Effect on Complication Development in Children Scheduled for Emergency and Urgent Surgery.

Objective: Although COVID-19 in childhood is often asymptomatic or has a more benign course, the safety of healthcare workers should be the primary goal because of the risk of contamination. In our study, we aimed to investigate the asymptomatic COVID-19 PCR positivity and its effect on the development of complications in emergency and non-deferred surgery cases that will help both the patient, the operating room and the health care workers. Material(s) and Method(s): This is a prospective study that was performed in patients under 18 years of age who were operated on due to emergency and urgent cases in the Ankara City Children's Hospital, which was serving as an anti-pandemic hospital. The patients were evaluated from May 1 to October 1, 2020. Of the 458 patients, 433 patients who met the criteria were included in the study. COVID-19 Nasopharyngeal swab (PCR) samples were taken from all patients along with preoperative examinations. Result(s): Of the 433 cases included in the study, 155 (33.5%) were girls and 278 (66.5%) were boys. It was determined that emergency cases constituted 389 (89.8%) of all cases. The most common emergency pathologies according to age groups were intestinal obstruction or atresia in the neonatal period, foreign body aspirations of the respiratory tract in the preschool period, and acute appendicitis in the school age. Nasal swab PCR results were positive in only four patients, this rate was found to be 0.9% in the entire study group, and postoperative complications and transmission to healthcare workers were detected at none. Conclusion(s): In this prospective study, low COVID-19 PCR positivity (0.9% prevalence) was detected in asymptomatic children scheduled for emergency or non-deferred surgery, and we believe that it will shed light on the planning of safe procedure practices. Copyright © 2021 Ankara Pediatric Hematology Oncology Training and Research Hospital. All rights reserved.

Postoperative Diffuse Peritonitis Causing Adhesive Bowel Obstruction Possibly Due to Sars-Cov-19 Infection: Report of a Case

Aim is to discuss diagnostic and therapeutic difficulties in COVID-19 related postoperative outcomes. A 5-year-old boy operated for jejunal atresia in neonatal period admitted with recurrent bilious vomiting. The upper GI series revealed dilated jejunum and absence of mechanical obstruction. The dilated jejunal segment was excised and anastomosis was performed. Later, he developed peritonitis without signs of anastomotic leaks. The second surgical exploration revealed diffuse peritonitis causing thickened and fibrous bowel loops causing hardly lysable adhesions. Then, his grandmother was learned to be COVID-PCR positive. Therefore, patients with atypical postoperative course should be investigated for possible COVID-19 during pandemics. Copyright © 2022 Ankara Pediatric Hematology Oncology Training and Research Hospital. All rights reserved.

Sarcopenia in Children with Liver Disease: A Pilot Study

Background and Aims Sarcopenia can be defined as loss of muscle mass, strength and function and has been shown to be associated with increased morbidity and mortality in the adult population. Sarcopenia has been assessed by decreased psoas muscle surface area (PMSA) on Computer tomography (CT) and has been validated in paediatric studies. The impact of Sarcopenia in children with end stage liver disease and oncological conditions is now being recognised. There is scarce literature on the effect of sarcopenia on motor function. CT imaging exposes children to radiation and hence is done in a select group of children at the time of transplant assessment. The aim of this audit was to assess the prevalence of Sarcopenia in children undergoing liver transplant assessment and its relationship on laboratory variables, functional activity and clinical outcomes. Methods Retrospective single centre case review of patients with liver disease undergoing transplant assessment and CT imaging between 2018-2020. Psoas muscle was analysed at the level of L4/L5. The z-Scores were calculated using ageand gender-specific reference values. Sarcopenia was defined as tPMA z score less than -2. We assessed the relationship of Sarcopenia to the biochemical parameters, nutritional status, effect on motor delay/physical abilities (assessed by a range of age appropriate standardised developmental and physical assessments due to COVID pandemic isolation restrictions) and post-transplant complications. Results Thirty one children that met the inclusion criteria were included. Sarcopenia was prevalent in 17 children (6 males: 11 females), with a median age of 3.5 years (SD = 4.9). The common conditions were biliary atresia (n= 11, 35%), hepatoblastoma (n=6, 19%), Autoimmune hepatitis (n=3) etc. Twenty- four patients required additional nutritional support (77% nasogastric feeding, 13% PN and 6% oral supplementation). Mean tPMA z-score was -2.27. Data for the assessment of physical abilities/functional activity was available in 21 children. Impairment of motor skills/physical abilities was overall noted in 14/21 children (67%);9/13 (69%) in the sarcopenic group (6 significant impairment) vs 5/8 (63%) in non sarcopenic group (4 significant impairment). Sarcopenia was associated with increased complications (27 vs 7, p = 0.005) and hypoalbuminaemia (p=0.01), but was not statistically significant (p> 0.05) for the overall length of stay (total and intensive care). Discussion Sarcopenia was commonly identified in children with liver diseases undergoing transplant assessment. Reduction in physical abilities/functional activity was observed in both groups which may be a consequence of loss of muscle mass in children secondary to liver diseases or underlying oncological conditions leading to delay in gross motor skills. Although there was no statistical difference in the duration of stay or impairment of motor skills, complications were higher in the sarcopenic group. Conclusion In this pilot study, sarcopenia is prevalent in children being assessed for liver transplantation and was associated with increased complications. Better non-invasive methods (aside from CT scan) of assessing sarcopenia needs to be developed and validated for the paediatric age group, which would help to better characterise the true incidence and prevalence of sarcopenia in children with chronic liver disease. There is a need to offer nutritional support and assess physical function early in the pre transplant period in order to initiate appropriate physiotherapy interventions to halt and even reverse the progression of sarcopenia.

GATA2 deficiency presenting as fever and rash

Case Report: Our patient is an 8-year-old Caucasian female with a history of choanal atresia, first degree heart block, recurrent urinary tract infections, and recent COVID-19 infection, who initially presented with an episode of syncope and vomiting. By history, she had two weeks of daily fever and an intermittent nonspecific rash. She was diagnosed with a UTI 5 days prior to presentation but had not defervesced despite treatment. Shewas initially found to be in shock with tachycardia and poor perfusion and was treated with fluid resuscitation, antipyretics, and empiric antibiotics. Labs were significant for leukopenia, elevated inflammatory markers, lactic acidosis, coagulopathy, and mildly elevated troponin. Chest x-ray showed abnormal but non-specific widespread infiltrates. She was initially treated with IVIG and pulse steroids for a working diagnosis of MIS-C, however she did not improve and a more extensive infectious, oncologic, and rheumatologic work-up was performed. Her workup revealed a disseminated Mycobacterium abscessus infection. Bone marrow biopsy revealed myelodysplasia with monosomy 7. Her buccal swab testing revealed a heterozygous germline mutation in the GATA2 gene, a variant that is predicted to cause loss of normal protein function. She is presently on multidrug regimen for her mycobacterial infection. Her myelodysplasia evolved into an acute leukemia, and she is undergoing chemotherapy for that at this time. Discussion(s): GATA2 deficiency, first identified in 2011, is a rare immune disorder resulting in a wide variety of clinical presentations. It is caused by a germline mutation of the GATA2 gene that disrupts blood cell differentiation, resulting in decreased or absent monocytes, B cells, NK cells, and dendritic cells1. This case presented multiple challenges due to the broad range of differential diagnoses. This patient was ultimately diagnosed with myelodysplastic syndrome associated with monosomy 7 and GATA2 deficiency, confirmed by FISH testing. Due to the presentation and lab derangements this patient had, there was a delay in targeted treatment while managing her cytopenias and presumed pulmonary infection. GATA2 deficiency carries a high risk of progression from myelodysplastic syndrome to acute myelogenous leukemia. The best long-term treatment for GATA2 deficiency is hematopoietic stem cell transplant, which is the ultimate goal for our patient. Copyright © 2023 Southern Society for Clinical Investigation.

A complicated tale of an acquired tracheoesophageal fistula: A case report

Background: Esophageal atresia (EA) with distal trachea-esophageal fistula (TEF), the most common variety of EA, is managed by primary end-to-end anastomosis. Recurrent TEF constitutes the most difficult-to-manage complication of the primary repair and has an incidence of 2% to15%. Case Presentation: We present a case of rare recurrent TEF after primary repair of EA. The difficulties faced in view of the COVID pandemic and difficult diagnosis are discussed. We share our experience in the successful management of acquired TEF and lessons learned. Conclusion: Recurrent trachea-esophageal fistula is one of the rare and challenging complications to manage. The surgical option carries the best overall prognosis. © 2022 Manchanda et al.

Incidence of Isolated Biliary Atresia during the COVID Lockdown in Europe: Results from a Collaborative Project by RARE-Liver.

BACKGROUND: Biliary atresia (BA) is a rare cholangiopathy where one of the proposed aetiological mechanisms is an infectious viral trigger. Coronavirus disease-19 (COVID) lockdown restrictions were implemented to reduce the transmission of infections. Strictness of lockdown varied across European countries. This study aimed to investigate if there was an association between strictness of lockdown and change in isolated BA (IBA) incidence in Europe. METHODS: We approached European centres involved in the European Reference Network RARE-LIVER. We included IBA patients born between 2015 and June 2020. We calculated the number of IBA patients born per centre per month. The Stringency Index (SI) was used as lockdown strictness indicator. The association between percentage change of mean number of IBA patients born per month and the SI was assessed. RESULTS: We included 412 IBA patients from thirteen different centres. The median number of patients per month did not change: 6 (1-15) pre-lockdown and 7 (6-9) during lockdown (p = 0.34). There was an inverse association between SI and percentage change in IBA (B = -0.73, p = 0.03). Median age at Kasai portoenterostomy (days) did not differ between time periods (51 (9-179) vs. 53 (19-126), p = 0.73). CONCLUSION: In this European study, a stricter COVID-lockdown was seemingly accompanied by a simultaneous larger decrease in the number of IBA patients born per month in the lockdown. Results should be interpreted with caution due to the assumptions and limitations of the analysis.

Left main coronary artery atresia in a 2-year-old toddler with de novo heart failure: Case report and review of the literature.

Congenital coronary anomalies are among the rare disorders of the otherwise normal heart. A 2-year-old toddler was evaluated for de novo heart failure after a flu-like event 2 months before being suspicious of post-Covid-19 dilated cardiomyopathy. The cardiac magnetic resonance (CMR) technique displayed the basal to mid subendocardial to transmural scar, suggestive of an ischemic etiology. Further assessment with CT and invasive angiography confirmed the very uncommon left main coronary artery atresia (LMCAA) as the main cause of the patient's heart failure. This is not only the first reported LMCAA case that had undergone a CMR study but was also initially suspected with characteristic CMR findings.

Outcome of children on the UK national prioritised paediatric registration tier

P69 Table 1Demographic and transplant data for all 14 prioritised patientsPatient/Sex Centre Age at registration (yrs) Primary liver disease Registered prior to Prioritisation Indication of Prioritization LT Waiting time on prioritised tier/Time on list prior to prioritisation 1/M 1 0 CDG Yes Acute decompensation with presence of encephalopathy Yes/LLS 5/27 2/M 2 1 Cryptogenic Cirrhosis Yes CLD with nodular lesions s/o HCC Yes/LLS 16/48 3/F 1 15 AILD Yes Chronic rejection Yes/whole liver 3/4 4/M 2 0 Biliary Atresia Yes PTLD/HAT/Sepsis Yes/LLS 14/71 5/F 2 4 IFALD No Coagulopathy with active bleeding/Renal impairment Yes/LLS 15/820 6/F 2 0 Biliary Atresia Yes Acute decompensation due to portal hypertension Yes/LLS 37/405 7/M 2 10 NSC Yes Decompensated chronic liver disease/Renal impairment Yes/reduced R lobe 4/7 8/M 3 8 PFIC3 Yes Acute decompensation of Chronic liver disease Yes/LLS 6/51 9/F 1 0 Other (Hepatoblastoma) Intestinal Tx prioritized Acute decompensation of Chronic liver disease Yes/LLS 11/ 10/F 2 0 Biliary atresia Yes Decompensated Chronic Liver Disease with Severe Coagulopathy Yes/LLS 10/120 11/M 1 0 Biliary atresia (Hepatoblastoma) Yes Acute decompensation of Chronic liver disease Yes/LLS 9/4 12/F 3 0 Biliary atresia Yes Acute decompensation of Chronic liver disease Yes/LLS 12/323 13/F 1 17 Hepatic Artery thrombosis Yes Hepatic Artery thrombosis Yes/whole liver 2/ 14/F 2 0 Biliary atresia Yes Acute decompensation of Chronic liver disease Suspended 12/65 PFIC3;Progressive Familial Intrahepatic Cholestasis type 3, LT;Liver transplantation, HCC;Hepatocellular Carcinoma NSC;Neonatal Sclerosing Cholangitis, CDG;Congenital Disorder of Glycosylation, AILD;Autoimmune Liver Disease, IFALD;Intestinal Failure Associated Liver Disease,PTLD;Center 1-Kings;Center2-Birmingham;Center3-Leeds.ConclusionThe national paediatric prioritization tier, introduced during the COVID19 pandemic, has been a pivotal initiative for the UK paediatric LT program, showcasing national collaboration. All patients underwent a LT successfully within a short time from prioritization with 100% patient and graft survival. The intention is to maintain this prioritized paediatric tier beyond the pandemic.

COVID-Related Neonatal Cholestasis?: Liver Transplantation in Three Infants with Intrauterine or Perinatal COVID Exposure

Purpose: The COVID pandemic presents a unique set of challenges during pregnancy including thromboembolic complications, direct placental infection, transplacental transmission, and systemic hyperinflammatory state. The liver is the second most commonly affected organ in COVID infection after the lungs. Mechanisms of liver injury in COVID-19 patients include: direct viral cytopathic effect, drug-induced hepatotoxicity, worsening of underlying liver disease, cytokine storm, hypoxic ischemic injury, and cholangiopathy. Post-COVID cholangiopathy leads to marked cholestasis with ongoing jaundice that persists long after other organs have recovered from infection. Method(s): We describe three infants at Texas Children's Hospital with intrauterine or perinatal COVID exposure with persistent cholestasis and extrahepatic biliary obstruction (mimicking biliary atresia), suggesting cholangiopathy. Result(s): All three patients described in this case series developed liver failure in the setting of low GGT cholestasis with histologic evidence of extrahepatic biliary obstruction, and all three required liver transplantation within the first year of life. Conclusion(s): Though post-COVID cholangiopathy is described in adults in the literature, our series is unique in that it is the first to describe this phenomenon in infancy. Additionally none of our infants had moderate or severe COVID infection but still progressed to advanced liver disease. Though further studies are needed to determine if additional factors are at play, our case series certainly raises the question of if the timing of exposure/infection might play a role in overall prognosis.

Esophageal Strictures in Children, a Six Year Case Series Experience in a Tertiary Center in Mexico City

Introduction: Esophageal strictures in children are in most cases associated with a benign etiology. There are multiple conditions that are associated with esophageal strictures including congenital stenosis, secondary to surgical repair of esophageal atresia, caustic burns following ingestion of acids or alcalis, radiation therapy and secondary to some pathologies as gastroesophageal reflux disease, eosinophilic esophagitis, scleroderma, epidermolysis bulllosa and idiopathic. Esophageal dilation can be performed with different techniques that include endoscope dilators, dilations performed over the wire and using the endoscope itself. Some cases require other adjunctive techniques that improve the results after failed progressive dilation. This therapies includes medical treatment and surgical derivations, with some cases known as recalcitrant. Also, esophageal strictures and its management could produce motility disorders. There is no consensus in the literature regarding the management process, especially in frequency of interventions, use of adjunctive therapies and alternatives for conservative management. This problem is more evident in developing countries. Objective(s): The objective of this study was to describe the cases of esophageal strictures and its management in children between 2016 and 2022 in the Instituto Nacional de Pediatria in Mexico City. Method(s): This was a six year retrospective study involving pediatric patients with esophageal stricture. We retrospectively reviewed the medical records of 23 pediatric patients who underwent endoscopic treatments for esophageal strictures, between January 2016 and May 2022 in the Comprehensive Pediatric Gastroenterology Diagnostic Unit in the Instituto Nacional de Pediatria in Mexico City. Result(s): The mean age at diagnosis was 24 months (Q1 15, Q3 35), 12 patients were male (52%) and 11 patients were female (48%). The most prevalent etiology was caustic strictures in 10 patients (43%). Six patients (26%) had esophageal atresia (4 type III, 1 type I and 1 type V), all whose received surgical management in the first days of life. All required repeated pneumatic dilation (between 1 and 11) for the management of postsurgical stenosis. Other etiologies that were found include Schatzki Ring, congenital stenosis, esophageal fibrosis associated with congenital dyskeratosis, epidermolysis bullosa, graft-versus-host disease and gastroesophageal reflux disease (one patient for each cause). In one patient the etiology remains unknown. Seventeen patients had one stricture, 5 patients had two strictures and 1 had 3 strictures. Ten patients had esophageal pseudodiverticula and two had mucosal fold. Six patients underwent dilation with Savary-Guilliard dilators combined with pneumatic balloon dilation. Four patients received mitomycin- C as an adjuvant therapy during dilations. The average diameter of stenosis was increased from 7 mm (range 4-15 mm) to 13,5 mm (range 8-18mm). Two patients had severe complications, one had a esophageal perforation associated with dilation. The other one had a pneumothorax related with anesthetic management. In the outcome 6 patients are asymptomatic, 1 patient persist with dysphagia after completed treatment, 9 patients are under treatment, 1 patient died secondary to its underlying disease and 6 patients lost follow up. Conclusion(s): Post-corrosive esophagitis and post-esophageal atresia anastomotic strictures were the most frequent types of cicatricial esophageal strictures. The conservative treatment was the first management strategy in the majority of patients, being the endoscopic balloon dilation the first choice. The SARS-COV-2 sanitary emergency limited the progressive intervention rate and appropriate clinical follow up of patients, reason why there is an important loss of follow up in the described group. A number of patients are currently on management, reason why their outcomes will be assessed in the future.

Turbinate hypertrophy following COVID-19 infection masks choanal atresia in adult.

A 34-year-old female 4 weeks post COVID-19 infection was diagnosed with inferior turbinate hypertrophy and a deviated nasal septum. The patient underwent inferior turbinate bone resection and nasal septoplasty with minimal improvement in nasal obstruction. Upon reevaluation, unilateral choanal atresia was discovered. Subsequent repair of the choanal atresia resolved all complaints of nasal obstruction. This unique presentation of a missed diagnosis of choanal atresia contributes to the idea that a variety of conditions may precede and at times delay the discovery of choanal atresia in adults.

Peritoneal Rupture of Hematocolpos in Distal Vaginal Atresia

An adolescent girl with vaginal atresia, massive hematocolpos and bilateral hydroureteronephrosis presented with an acute abdomen secondary to spontaneous rupture of the hematocolpos into the cul-de-sac. Diagnosis, treatment, postoperative course and complications of this unique case are briefly summarized. Spontaneous rupture of hematocolpos into the abdominal cavity is an extremely rare manifestation of vaginal atresia. Tertiary care management, which involves a multidisciplinary team of experienced gynecologists, plastic surgeons, urosurgeons, and critical care physicians, is recommended for optimal management of these patients. Patient education is also crucial;regular follow-ups visits and strict adherence to the postoperative vaginal dilatation schedule can reduce risk of stenosis after vaginoplasty.

Development and diseases of the coronary microvasculature and its communication with the myocardium.

We review the current understanding of formation and development of the coronary microvasculature which supplies oxygen and nutrients to the heart myocardium and removes waste. We emphasize the close relationship, mutual development, and communication between microvasculature endothelial cells and surrounding cardiomyocytes. The first part of the review is focused on formation of microvasculature during embryonic development. We summarize knowledge about establishing the heart microvasculature density based on diffusion distance. Then signaling mechanisms which are involved in forming the microvasculature are discussed. This includes details of cardiomyocyte-endothelial cell interactions involving hypoxia, VEGF, NOTCH, angiopoietin, PDGF, and other signaling factors. The microvasculature is understudied due to difficulties in its visualization. Therefore, currently available imaging methods to delineate the coronary microvasculature in development and in adults are discussed. The second part of the review is dedicated to the importance of the coronary vasculature in disease. Coronary microvasculature pathologies are present in many congenital heart diseases (CHD), especially in pulmonary atresia, and worsen outcomes. In CHDs, where the development of the myocardium is impaired, microvasculature is also affected. In adult patients coronary microvascular disease is one of the main causes of sudden cardiac death, especially in women. Coronary microvasculature pathologies affect myocardial ischemia and vice versa; myocardial pathologies such as cardiomyopathies are closely connected with coronary microvasculature dysfunction. Microvasculature inflammation also worsens the outcomes of COVID-19 disease. Our review stresses the importance of coronary microvasculature and provides an overview of its formation and signaling mechanisms and the importance of coronary vasculature pathologies in CHDs and adult diseases. This article is categorized under: Cardiovascular Diseases > Stem Cells and Development Congenital Diseases > Molecular and Cellular Physiology Cardiovascular Diseases > Molecular and Cellular Physiology.