Bilateral Pulmonary Arteriovenous Malformations: Challenges in a Rare and Complex Case.

Pulmonary arteriovenous malformations (PAVMs) are abnormal vascular connections between the pulmonary arteries and pulmonary veins. Despite their relatively uncommon incidence, PAVMs should be considered in the differential diagnosis of children presenting with cyanosis due to the life-threatening complications posed by paradoxical emboli. The primary management approach involves eliminating the abnormal connections, either through surgical or endovascular methods. We present a case of a five-year-old boy who was seen in the Outpatient Department with cyanosis of the lips and nail beds persisting for eight months. On examination, grade 3 clubbing was noted. Imaging and subsequent angiography revealed multiple bilateral diffuse AVMs, which were treated using an endovascular approach.

Research progress of the relationship between phosphoprotein phosphatases (PPPs) and neurodevelopmental disorders.

Reversible protein phosphorylation is a ubiquitous phenomenon essential for eukaryotic cellular processes. Recent advancements in research about neurodevelopmental disorders have prompted investigations into the intricate relationship between protein phosphatases, particularly phosphoprotein phosphatases (PPPs), and neurodevelopment. Notably, variants in 10 coding genes spanning four PPP family members have been implicated in neurodevelopmental disorders. Here, we provide a comprehensive overview of the clinical phenotypes, genotypes, and pathogenic mechanisms observed in affected patients. Our analysis reveals challenges in subsequent statistical analyses due to inconsistent clinical phenotypic descriptions and a lack of large multicenter studies, hampering analysis about genotype-phenotype correlations. The scarcity of follow-up data poses a significant obstacle to prognostic counseling for nearly all rare diseases. Presently, symptomatic treatment strategies are employed for patients with variants, as definitive cures remain elusive. Future research may explore protein phosphatase regulators as potential therapeutic targets. Furthermore, it is imperative not to overlook other members of the protein phosphatase family or coding genes with undiscovered variants. Insights gleaned from the temporal and spatial distribution of proteins, along with observations from animal model phenotypes, may provide valuable directions for uncovering novel pathogenic genes.

Suspicion diagnostic of Hirschsprung's disease in an adult intraoperatively: A case report.

Background: Hirschsprung disease, a developmental disorder affecting the neuronal ganglion cells in distal colon, is the leading cause of intestinal obstruction in newborns, predominantly males, although the diagnosis can be made lately in rare cases. We describe an adult Hirschsprung disease case found intraoperatively. Case description: He is a 20-year-old male patient with past medical history of epilepsy, psychomotor delay and recently a perineal perforating injury, admitted in the emergency room with initial diagnosis of peritonitis by perforated viscus with Frankel grad B spinal cord injury. Among his initial signs and symptoms were abdominal distension, rebound tenderness, decreased bowel sounds and diffuse pain. Laboratory tests revealed increased Hb, decreased white cells count and increased creatinine level. Initial management included: fluid resuscitation, analgesics, antibiotics and laxatives. After becoming hemodynamically unstable, the patient was introduced to the operating room where a highly dilated rectum with areas of necrosis at the base was discovered after access to the abdominal cavity. While doing the intervention, the patient experienced 3 cardiac arrests following by successful ressucitation and blood transfusion; leading to the decision to delay the definitive closure using the Bottega technique. The surgical course was unfavorable as the patient died around 4 hour post-surgery. Conclusion: Hirschsprung disease in adult, due to its rarity and its overlapping features with many other conditions that can affect the GI system, can be misdiagnosed or discovered lately. A thorough evaluation by an appropriate specialist is essential for adequate diagnosis and management.

Congenital Absence of Pericardium: The Swinging Heart.

Congenital absence of the pericardium (CAP) is an unusual condition discovered, in most cases, incidentally but can potentially lead to fatal complications, including severe arrhythmias and sudden death. Recently, the use of modern imaging technologies has increased the diagnosis of CAP, providing important findings for risk stratification. Nevertheless, there is not yet consensus regarding therapeutic decisions, and the management of patients with CAP remains challenging. In this paper, we discuss the pathophysiological implication of CAP, review the current literature and explain the role of multimodality imaging tools for its diagnosis, management and treatment.

Scimitar Syndrome in Adulthood: Challenges in Management and Individualized Approaches.

Scimitar syndrome is a congenital disorder characterized by partial anomalous pulmonary venous return to the inferior vena cava (IVC). Clinical manifestation in adulthood is infrequent. The management approach has not been universally accepted and may be challenging. Individually tailored and multidisciplinary team-based decisions are often necessary. We present the case of a symptomatic patient diagnosed with complex congenital heart disease, including scimitar syndrome and atrial septal defect at the age of 50 years. Surgical repair, involving scimitar vein implantation in the left atrium using a pericardial patch, was performed. Despite surgical correction, dyspnea persisted, and hemoptysis developed. A diagnostic workup revealed a critical stenosis of the re-inserted vein. This was successfully treated by percutaneous intervention with stent implantation. The patient has remained asymptomatic since the procedure. Scimitar syndrome can be first diagnosed in adulthood, and clinical manifestations can vary. Diagnostic workup necessitates a CT angiogram, magnetic resonance scan, and catheterization in selected cases. Stenoses of re-implanted pulmonary veins (PVs) can develop years after surgical correction, and hemoptysis may serve as a warning symptom prompting further PV imaging. Percutaneous vascular intervention using a stent is warranted in symptomatic cases and can lead to long-term success.

Polyorchidism in a young Sprague-Dawley rat.

Duplicate testes lined in series were observed in the right scrotum of a 6-week-old Sprague-Dawley rat in a single-dose toxicity study. Of the two right testicles, one was spherical and less than half the size of a normal testis. The other was oval-shaped, slightly smaller than a normal testis, and possessed clear, tortuous blood vessels similar to those of a normal testis. Each right testis was grossly separated but faced the intertesticular adipose tissue and was sparsely joined by thin cord-like structures. Only one epididymis covered or encompassed the two right testes. The caput epididymis was attached to the smaller spherical testis, whereas the cauda epididymis was attached to the oval testis. Histopathological examination revealed that the smaller spherical testis on the right side and the testis on the left side were normal. The oval-shaped testis on the right exhibited markedly dilated degenerative seminiferous tubules with one to two layers of Sertoli or germ cells, and almost no spermatogenesis was observed. Multinucleated germ cells were observed in the lumen of the degenerated seminiferous tubules. The right epididymis was morphologically normal and contained few sperm in the epididymal duct of the tail. The cord-like structures between duplicate testes comprised fibrous and adipose tissues. Single efferent ductules, ectopic cartilage, and skeletal muscle tissues were buried in the adipose tissue. To our knowledge, this is the first report of spontaneous polyorchidism in a rodent.

A Closer Look at Aplasia Cutis Congenita: Understanding a Unique Case.

Aplasia cutis congenita (ACC) is a rare congenital disease defined by the absence of skin, most commonly on the scalp. While the exact incidence remains uncertain, ACC presents a significant challenge in clinical management due to its variable presentation and associated complications. We present the case of a newborn male with a large scalp defect attributed to ACC, complicated by a life-threatening scalp hemorrhage. Despite challenges in management, including recurrent infections and failed skin grafts, the patient ultimately achieved satisfactory healing following a series of surgical interventions, including local transposition flap procedures. This case underscores the importance of a multidisciplinary approach to managing ACC, tailored to individual patient characteristics and associated risks. While discrete lesions of ACC typically have a favorable prognosis, extensive defects pose significant risks of morbidity and mortality, highlighting the need for careful consideration of treatment options and close clinical monitoring of affected individuals.

In utero delivery of targeted ionizable lipid nanoparticles facilitates in vivo gene editing of hematopoietic stem cells.

Monogenic blood diseases are among the most common genetic disorders worldwide. These diseases result in significant pediatric and adult morbidity, and some can result in death prior to birth. Novel ex vivo hematopoietic stem cell (HSC) gene editing therapies hold tremendous promise to alter the therapeutic landscape but are not without potential limitations. In vivo gene editing therapies offer a potentially safer and more accessible treatment for these diseases but are hindered by a lack of delivery vectors targeting HSCs, which reside in the difficult-to-access bone marrow niche. Here, we propose that this biological barrier can be overcome by taking advantage of HSC residence in the easily accessible liver during fetal development. To facilitate the delivery of gene editing cargo to fetal HSCs, we developed an ionizable lipid nanoparticle (LNP) platform targeting the CD45 receptor on the surface of HSCs. After validating that targeted LNPs improved messenger ribonucleic acid (mRNA) delivery to hematopoietic lineage cells via a CD45-specific mechanism in vitro, we demonstrated that this platform mediated safe, potent, and long-term gene modulation of HSCs in vivo in multiple mouse models. We further optimized this LNP platform in vitro to encapsulate and deliver CRISPR-based nucleic acid cargos. Finally, we showed that optimized and targeted LNPs enhanced gene editing at a proof-of-concept locus in fetal HSCs after a single in utero intravenous injection. By targeting HSCs in vivo during fetal development, our Systematically optimized Targeted Editing Machinery (STEM) LNPs may provide a translatable strategy to treat monogenic blood diseases before birth.

Transitional Urology in Korea: Initial Insights Through a Cross-Sectional Study.

PURPOSE: In Korea, the field of transitional urology (TU) is in its nascent stages, with its introduction only beginning. This study aims to evaluate the existing state of TU prior to implementing a transition protocol, and to identify key areas of focus for the development of an effective transition protocol. METHODS: From June 1, 2021 to May 31, 2023, clinical data were retrospectively collected for patients who visited the adult urology or pediatric urology outpatient departments of this hospital and were aged 10 or older, with medical conditions falling under the category of TU. We analyzed the patient distribution across different disease groups. The transitional stages were categorized from T1, indicating initial care by pediatric urologists, to T4, denoting complete transition to adult care. 'T4x' was used for patients with unknown medical histories, and 'T4only' for those who had never been under pediatric urology care. RESULTS: During a 2-year period, a total of 1,484 patients received outpatient care for diseases in TU field. The most prevalent diseases were hypospadias (40.4%), spinal bifida (37.3%), and congenital ureteral anomalies (17.7%), with other conditions accounting for 4.6%. Among 553 spinal bifida patients, only 5.3% completed transitional care (T4), while 80.1% were in the initial phase (T1). For patients introduced to adult urology (T2-T4), 37.7% reached T4, highlighting a marked increase in transition completion within this subset (P<0.001). CONCLUSION: TU in Korea is in its nascent stage, with a significant gap in the initiation and completion of transitional care for patients with congenital urologic conditions. Early initiation and active engagement in transitional care are crucial for successful transition. This study highlights the need for structured transition protocols to address the complex needs of this patient population.

Case report: Small bowel obstruction secondary to congenital transmesenteric internal hernia in a cat.

An 8-month-old castrated male British Shorthair cat presented with acute anorexia and vomiting. The overall clinical presentation included generalized depression. Physical examination revealed palpable abdominal mass, thus foreign body or intussusception was suspected. Abdominal radiographs showed segmental dilation of small intestine and ultrasonography revealed target lesion with dilated small bowel loops and disrupted normal wall layering, suggestive of intussusception. Exploratory laparotomy confirmed congenital mesenteric defects associated with small intestinal obstruction. Surgical intervention involved dissection, ligation of encircling blood vessels, and closure of mesenteric defects. The cat was discharged after 3 days, exhibiting normal postoperative recovery. To our knowledge, this is the first case report of congenital mesenteric defect associated with small intestinal obstruction in a cat. While internal hernias are rare, it is essential to include them in the differential diagnosis for cases of intestinal obstruction, particularly in patients with no history of previous surgery or trauma. The potential for strangulation and ischemia in the affected loops elevates internal hernias to a critical, life-threatening condition, emphasizing the need for prompt recognition and urgent surgical intervention as an emergency.

Statewide Hospital Admissions for Adult Survivors of Infant Surgical Diseases Over a 10-Year Period.

INTRODUCTION: The number of patients with congenital disease living to adulthood continues to grow. Often undergoing surgical correction in infancy, they continue to require lifelong care. Their numbers are largely unknown. We sought to evaluate hospital admissions of adult patients with esophageal atresia with tracheoesophageal fistula (EA/TEF), congenital diaphragmatic hernia (CDH), and Hirschsprung disease (HD). METHODS: The Florida Agency for Healthcare Administration inpatient database was merged with the Distressed Communities Index and Centers for Medicare and Medicaid Services Hospital and Physician Compare datasets. The dataset was queried for adult patients (≥18 y, born after 1970) with EA/TEF, CDH, and HD in their problem list from 2010 to 2020. Patient demographics, hospitalization characteristics, and discharge information were obtained. RESULTS: In total, 1140 admissions were identified (266 EA/TEF, 135 CDH, 739 HD). Patients were mostly female (53%), had a mean age of 31.6 y, and often admitted to an adult internist in a general hospital under emergency. Principal diagnoses and procedures (when performed) varied with diagnosis and age at admission. EA patients were admitted with dysphagia and foregut symptoms and often underwent upper endoscopy with dilation. CDH patients were often admitted for diaphragmatic hernias and underwent adult diaphragm repair. Hirschsprung patients were often admitted for intestinal obstructive issues and frequently underwent colonoscopy but trended toward operative intervention with increasing age. CONCLUSIONS: Adults with congenital disease continue to require hospital admission and invasive procedures. As age increases, diagnoses and performed procedures for each diagnoses evolve. These data could guide the formulation of multispecialty disease-specific follow-up programs for these patients.

Borrelia burgdorferi colonizes the mammary glands of lactating C3H mice: does not cause congenital Lyme disease.

Transplacental transmission of syphilis causing spirochete, Treponema pallidum subspecies pallidum, from mother to child results in congenital syphilis, an ever-expanding devastating disease worldwide. Although adverse effects of untreated gestational Lyme disease, caused by a related spirochete, Borrelia burgdorferi on fetus viability and development have been observed, cases of congenital Lyme disease are not reported. In this study, we show that B. burgdorferi colonizes mammary glands of C3H mice only postpartum; however, neither transmission of these spirochetes from dams-to-pups occurs nor congenital Lyme disease is observed in pups.

A supervised learning method for classifying methylation disorders.

BACKGROUND: DNA methylation is one of the most stable and well-characterized epigenetic alterations in humans. Accordingly, it has already found clinical utility as a molecular biomarker in a variety of disease contexts. Existing methods for clinical diagnosis of methylation-related disorders focus on outlier detection in a small number of CpG sites using standardized cutoffs which differentiate healthy from abnormal methylation levels. The standardized cutoff values used in these methods do not take into account methylation patterns which are known to differ between the sexes and with age. RESULTS: Here we profile genome-wide DNA methylation from blood samples drawn from within a cohort composed of healthy controls of different age and sex alongside patients with Prader-Willi syndrome (PWS), Beckwith-Wiedemann syndrome, Fragile-X syndrome, Angelman syndrome, and Silver-Russell syndrome. We propose a Generalized Additive Model to perform age and sex adjusted outlier analysis of around 700,000 CpG sites throughout the human genome. Utilizing z-scores among the cohort for each site, we deployed an ensemble based machine learning pipeline and achieved a combined prediction accuracy of 0.96 (Binomial 95% Confidence Interval 0.868[Formula: see text]0.995). CONCLUSION: We demonstrate a method for age and sex adjusted outlier detection of differentially methylated loci based on a large cohort of healthy individuals. We present a custom machine learning pipeline utilizing this outlier analysis to classify samples for potential methylation associated congenital disorders. These methods are able to achieve high accuracy when used with machine learning methods to classify abnormal methylation patterns.

Newborns with congenital complete heart block: Advice for perinatal care providers.

Congenital complete heart block (CCHB) is a rare, but a potentially life-threatening manifestation of autoimmune diseases in neonates. Bradycardia in CCHB can be misdiagnosed as foetal distress in utero and thus precipitating a Caesarean section. We report a case series of three neonates with bradycardia without any electrolyte abnormalities and structurally normal hearts with favourable outcomes.

The protocol of Enhanced Recovery After Cardiac Surgery (ERACS) in congenital heart disease: a stepped wedge cluster randomized trial.

BACKGROUND: The Enhanced Recovery After Cardiac Surgery (ERACS) programs are comprehensive multidisciplinary interventions to improve patients' recovery. The application of the ERAS principle in pediatric patients has not been identified completely. METHODS: This study is a multicenter, stepwise design, cluster randomized controlled trial. 3030 patients presenting during control and intervention periods are eligible if they are aged from 28 days to 6 years old and awaiting elective correction surgery of congenital heart disease with cardiopulmonary bypass. 5 centers are randomly assigned to staggered start dates for one-way crossover from the control phase to the intervention phase. In the intervention periods, patients will receive a bundle strategy including preoperative, intraoperative, and postoperative approaches. During the control phase, patients receive the usual care. The primary outcome consists of major adverse cardiac and cerebrovascular events (MACCEs), postoperative pulmonary complications (PPCs), and acute kidney injury (AKI). DISCUSSION: This study aims to explore whether the bundle of ERAS measurements could improve patients' recovery in congenital heart surgery. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov . (NCT05914103).

Síndrome Klippel-Trenaunay en el embarazo. Reporte de un caso y revisión de la literatura / Klippel-Trenaunay syndrome in pregnancy. Case report and literature review

Resumen Antecedes: El síndrome de Klippel-Trenaunay (KTS) es un síndrome de malformación vascular que comprende una afectación variable de capilares cutáneos, venas y linfáticos con hipertrofia de tejidos blandos y huesos de la extremidad afectada. Durante el embarazo estas malformaciones se incrementan, con afectación pélvica e intraabdominal. Caso clínico: Paciente de 15 años, primigesta, con síndrome Klippel-Trenaunay diagnosticado al nacimiento, con embarazo a término, referida por iniciar con trabajo de parto para finalización del embarazo en un hospital de tercer nivel. No cuenta con control obstétrico, estudios prenatales ni ultrasonidos obstétricos. Se realiza una ecografía pélvica en donde se descartóla presencia de varices pélvicas y un doppler que evidenció un sistema venoso conservado. Se realiza terminación del embarazo vía abdominal obteniendo un recién nacido vivo masculino, peso de 3045 gramos, APGAR 9 y 9 al minuto y a los 5 minutos. Resultados: El embarazo en pacientes con síndrome de Klippel-Trenaunay tiene alto riesgo de tromboembolismo y complicaciones hemorrágicas. La valoración debe ser por un equipo multidisciplinario capacitado para anticiparse a las potenciales complicaciones. Limitaciones del estudio o implicaciones: La principal limitación es la baja incidencia de esta patología. Se puede concluir que el diagnostico de SKT no es indicación de interrupción del embarazo. El éxito del manejo de estas pacientes requiere la participación de un equipo multidisciplinario. Originalidad o valor: Este caso clínico es de primordial relevancia ya que en la bibliografía internacional están reportados menos de 100 casos de embarazos complicados con este síndrome.

Abstract: Background: Klippel-Trenaunay syndrome (KTS) Klippel- Trenaunay syndrome (KTS) is a vascular malformation síndrome that includes variable involvement of skin capillaries, veins and lymphatics with hypertrophy of soft tissues and bones of the affected limb. During pregnancy, these malformations increase, with pelvic and intra-abdominal involvement. Clinical case: 15-year-old patient, gravida 0, with Klippel- Trenaunay syndrome diagnosed at birth, with full-term pregnancy, referred for initiating labor for resolution of pregnancy in a third level hospital. Without obstetric control, without prenatal studies or obstetric ultrasounds. A pelvic ultrasound was performed, which ruled out the presence of pelvic varices and a Doppler that showed a preserved venous system. The pregnancy was terminated by abdominal route, obtaining a male newborn, weighting 3045 grams, APGAR 9 and 9 after 1 and 5 minutes. Results: Pregnancy in patients with Klippel-Trenaunay síndrome has a high risk of thromboembolism and bleeding complications. They should be evaluated by a trained multidisciplinary team to anticipate possible complications. Study limitations or implications: The main limitation is the low incidence of this pathology. It can be concluded thatthe diagnosis of SKT is not an indication for termination of pregnancy. Successful management of these patients requires the participation of a multidisciplinary team. Originality or value: This clinical case is of primary relevance since fewer than 100 cases of complicated pregnancies with this syndrome are reported in the international literature.

La escleroterapia como opción terapéutica en el manejo del síndrome de Klippel-Trenaunay / Sclerotherapy as a therapeutic option in the management of Klippel-Trenaunay syndrome

Introducción: El síndrome de Klippel-Trenaunay es una enfermedad congénita poco frecuente, caracterizada por una tríada clásica, que consiste en una malformación capilar cutánea, hipertrofia del tejido blando y/u óseo en extremidades, y malformaciones venosas, resultantes en venas varicosas u otras malformaciones del sistema venoso profundo. Objetivo: Presentar la escleroterapia como opción terapéutica en el manejo del síndrome de Klippel-Trenaunay. Métodos: Paciente femenina de 27 años, color de piel blanca, con antecedentes de diagnóstico de Síndrome de Klippel-Trenaunay desde los tres años de edad, el cual se manifestó como un nevus desde su nacimiento, localizado en la región glútea izquierda, aumento de tamaño de la extremidad y presencia de dilataciones venosas desde la infancia temprana. Resultados: Se empleó, como tratamiento de las várices, la escleroterapia con espuma. Conclusiones: Se logró eliminar los trayectos varicosos, mejorando la estética y funcionabilidad de la extremidad(AU)

Introduction: Klippel-Trenaunay syndrome is a rare congenital disease characterized by a classic triad consisting of a cutaneous capillary malformation, hypertrophy of soft tissue and/or bone in the limbs, and venous malformations, resulting in varicose veins or other malformations of the deep venous system. Objective: To present sclerotherapy as a therapeutic option in the management of Klippel-Trenaunay syndrome. Methods: It is presented the case of a 27-year-old female patient, with white skin, a history of diagnosis of Klippel-Trenaunay syndrome since she was three years old, which manifested as a nevus from birth, located in the left gluteal region, increased size of the limb and presence of venous dilations since early childhood. Results: Foam sclerotherapy was used as a treatment for varicose veins. Conclusions: Varicose tracts were eliminated, which improved the aesthetics and functionality of the limb(AU)

Pyopneumothorax Secondary to Pulmonary Tuberculosis Superadded by Congenital Factor XIII Deficiency: A Case Report.

Pyopneumothorax is a rare complication of pulmonary tuberculosis, contributing significantly to morbidity and mortality. Additionally, factor XIII deficiency, a rare bleeding disorder, may pose a diagnostic challenge due to normal results in routine coagulation tests. We present the case of an 18-year-old boy who presented with a history of left-sided pyopneumothorax secondary to drug-sensitive Mycobacterium tuberculosis, complicated by congenital factor XIII deficiency. After three months of intercostal drainage placement, the patient developed severe anemia and bleeding tendencies, necessitating a referral to clinical hematology. Genetic testing revealed factor XIII deficiency. This case highlights the complicated interplay between tuberculosis-related complications and a coexisting genetic disorder, highlighting the importance of comprehensive clinical assessment and multidisciplinary management.