ACTA2 Alliance’s Post

Researchers from the University of Edinburgh have revealed that improved patient care is needed to reduce cancer risk among women with endometrial hyperplasia in a new study. The study compared the treatment that patients living with the condition received before and after the introduction of national guidance. Grouped into two types, atypical endometrial hyperplasia is a precancerous condition that carries an increased risk, and non-atypical endometrial hyperplasia occurs when the womb lining is thicker than normal but less likely to become cancerous. Currently, in the UK, the national guidance for this condition recommends a hysterectomy, a surgical procedure that removes the womb, for patients with atypical endometrial hyperplasia. For those with non-atypical endometrial hyperplasia, guidance recommends a trial of a hormone treatment given directly into the womb, with regular follow-up monitoring to track progress. The study analysed patient records from more than 3,000 people across the UK diagnosed with endometrial hyperplasia between 2012 and 2020, 50% of whom had non-atypical endometrial hyperplasia and the other half had atypical. Non-atypical endometrial hyperplasia patients who had hormone treatment increased from 38% to 53% after the UK national guidelines were introduced, while hysterectomy surgery for atypical patients was reduced by 1% between 2012 and 2015 and 2016 and 2019. At the start of the COVID-19 pandemic in 2020, hysterectomy surgery for endometrial hyperplasia patients had dropped to 52%. Researchers then revealed that only one in five women with the condition who did not have a hysterectomy received the recommended schedule of follow-up monitoring and biopsies, while 37% who did receive a hysterectomy between 2016 and 2019 showed evidence of cancer when their wombs were analysed after surgery. Read more: https://lnkd.in/ehHtMuHN Stay in touch with all the leading stories, events and opportunities by subscribing to our LinkedIn Newsletter here: https://bit.ly/3RbdKtc

Free pdf in link. While identifying hereditary #cancer predisposition in individuals with #hematologic #malignancies (HM) is critical for optimal clinical management 1-5, #genetic #genetesting for these individuals in limited, in part, by the difficulty in obtaining #dna suitable for germline analysis. Peripheral blood, saliva and buccal swabs are often contaminated with malignant cells in patients with HM 6 . Cultured fibroblasts obtained through skin biopsies are used for germline testing of patients with HM, although the invasive nature of the procedure and the multiple weeks-long culturing time before testing can be performed limits the utility of this specimen. Nail clippings represent a non-invasive source of DNA that can be used for germline testing 7,8. Here, we describe a novel, clinically validated, and New York State Department of Health approved #nextgenerationsequencing assay for germline testing of patients with HM using DNA isolated from nail clippings. We describe the institution-wide implementation of this assay, the initial clinical findings in this cohort, and the clinical benefit experienced by these patients due to expanded genetic testing. We describe the development of a novel high-throughput germline testing assay for individuals with HMs using nail DNA. Currently, DNA from cultured fibroblasts obtained through skin biopsies is the most commonly used specimen type for germline testing in patients with active HM, although the invasive nature of the procedure and the multiple weeks- 9 long culturing time make it challenging to utilize on a large scale and deliver results in a timely fashion. In a recent study, the median turnaround time for fibroblast culture alone was 28 days and 5% of skin biopsies failed to culture, resulting in the need for an additional biopsy 15. The median turnaround time of 10 workdays for our test was substantially lower than the amount of time needed for a fibroblast culture and testing time in a typical skin biopsy test. Our rapid and noninvasive germline testing approach allows for an institution-wide initiative towards universal genetic testing for patients with HMs. Remarkably, in the first 240 consecutive patients with HM who consented to genetic testing, a similar proportion tested positive for hereditary cancer susceptibility (17.1%) as in our patients with solid tumors (16.7%) tested under the same IRB protocol 16. Even in this initial cohort, germline findings resulted in therapeutic considerations, initiation of surveillance for additional malignancies, and identification of at-risk relatives.  https://lnkd.in/eDCnp-Ub The National Institutes of Health #nih National Cancer Institute (NCI) #genomics #biospecimens American Cancer Society

#stemcells treatment using cord blood has shown promise in the treatment of various pediatric diseases. Cord blood is a rich source of hematopoietic stem cells, which can differentiate into all types of blood cells. These stem cells can be used to rebuild a patient's blood and immune system, making cord blood an attractive option for the treatment of pediatric diseases that affect these systems. One of the most common uses of cord blood stem cell therapy in pediatrics is in the treatment of pediatric cancers, such as leukemia and lymphoma. Cord blood transplantation has been shown to be effective in treating these diseases, particularly in cases where a matched donor is not available. Cord blood stem cells have also been used to treat other pediatric diseases, including sickle cell disease, thalassemia, and inherited metabolic disorders. Cord blood stem cell therapy has several advantages over traditional bone marrow transplantation. Cord blood is easier to collect and store than bone marrow, and the stem cells are less likely to be rejected by the recipient's body. Additionally, cord blood stem cells are more flexible than adult stem cells, which means they can be used to treat a wider range of diseases. However, there are also some limitations to cord blood stem cell therapy. One major limitation is the limited number of stem cells that can be obtained from a single cord blood unit. This can lead to slower engraftment and a higher risk of infection and other complications. Additionally, the success of cord blood transplantation depends on the degree of matching between the donor and recipient, and the availability of matched cord blood units can be limited. Despite these limitations, cord blood stem cell therapy has shown great potential in the treatment of pediatric diseases. Ongoing research is focused on developing new techniques to expand the number of stem cells that can be obtained from a single cord blood unit, as well as improving the matching process to increase the likelihood of successful transplantation. Overall, cord blood stem cell therapy represents a promising avenue for the treatment of pediatric diseases and holds great potential for improving outcomes for children with these conditions. #cordblood #pediatrics #pediatriccancer #pediatricblooddiseases #cordbloodtransplant #cordbloodbankinguae #cordbloodbankingexpert #publiccordbloodbanking #cordbloodregistry #stemcells #stemcellstransplant #stemcelltreatment #stemcelleducation #cordbloodawarness #privatecordbloodbanking

CLOVES Syndrome: Breaking Down Barriers and Building Hope CLOVES Syndrome, which stands for Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevis, Spinal/Skeletal Anomalies/Scoliosis, is a genetic disorder which causes enlargement of fatty tissues, vascular malformations, and other skin and skeletal abnormalities. It is extremely rare, having only recorded 200 cases worldwide. CLOVES was first identified in 2009, by a clinical and research team led by Dr. Ahmad Alomari, MD. But reports identifying the symptoms of CLOVES are dated much earlier, with the first account being written by German physician Hermann Friedberg on “gigantism of the right lower limb.” HOW IS IT CAUSED? Its cause is thought to be mutations to the PIK3CA gene. The PIK3CA gene codes for p110 alpha, a protein in the enzyme phosphatidylinositol 3-kinase (PI3K). This enzyme plays an important role in cell growth, proliferation and movement. Abnormal production of this enzyme can lead to cancerous growth; mutations in this gene have been identified in various types of cancer including ovarian, breast, lung and brain. In CLOVES however, uncontrolled cell growth caused by the mutations lead to growth of fatty masses, lymphatic malformations, asymmetric kidneys, spinal anomalies (caused by scoliosis or fatty masses pushing into the spinal cord), and in some cases asymmetric face and head. DIAGNOSIS: The diagnosis is evident at birth based on physical signs and symptoms. Confirmation of diagnosis can be done with molecular genetic testing for the PIK3CA gene mutation. Imaging studies include plain x-rays (radiography), magnetic resonance imaging (MRI) of the chest, abdomen, pelvis, spine and limbs and ultrasound for vascular anomalies and kidneys. Prenatal diagnosis with imaging tools is feasible. TREATMENTS: • Oral drugs (rapamycin) that suppress the immune system and lessen the growth of abnormal lymphatic vessels, sclerotherapy, embolization, debulking surgery, and inferior vena cava (IVC) filters to prevent embolisms. • Sclerotherapy. This treatment involves injecting a solution directly into the venous mass to make it shrink. • Embolization. This procedure blocks blood vessels or vascular channels of malformations. Due to how obscure this condition is, the symptoms are often misdiagnosed. Hence, it becomes essential to spread awareness so it can be treated correctly. In 2010 the CLOVES Syndrome Community (CSC) established Cloves Syndrome Awareness Day, which is celebrated annually on 3 August. It strives to raise awareness about the challenges faced by those suffering from CLOVES, and to promote research into improving diagnosis and treatment of the disorder. References: https://lnkd.in/gwZfajZb https://lnkd.in/g4HJavPG Written by: Shruti Sathyanarayanan

Reirradiation of the brain in pediatric patients: What constraints to use? With increasingly effective treatments against pediatric cancer (with greater OS and PFS), we encounter patients who live longer and face relapses, with local relapses, i.e., the need to treat previously treated areas, presenting a greater technical challenge. The scenario of reirradiation has historically been complex. From the paradigm of NOT REIRRADIATING, we have evolved with the advent of conformal techniques such as IMRT and new energies such as proton therapy, towards the feasibility of reirradiation, but without having firm evidence on safe constraints to plan a treatment. In this article published in February 2024, a systematic review was conducted finding 17 articles reporting brain and brain stem necrosis after reirradiation. Results: The average prescription dose EQD2 was 103.8 Gy. Out of 449 patients, 22 (4.9%) developed brain necrosis and 14 (3.1%) developed brain stem necrosis. Median follow-up of 1.6 years (range, 0.5-7.4 years). The median cumulative prescription EQD22 was 111.4 Gy for the development of any necrosis. EQD2 was 107.7 Gy for brain necrosis. EQD2 was 112.1 Gy for brain stem necrosis. The median latent period between reirradiation and the development of necrosis was 5.7 months. Though there were more events among children/AYA undergoing hypofractionated versus conventionally fractionated reirradiation, the differences were not statistically significant (P = .46). Conclusions: Existing reports suggest that in children/AYA with recurrent brain tumors, reirradiation with a total EQD22 of about 112 Gy is associated with an approximate 5% to 7% incidence of brain/brain stem necrosis after a median follow-up of 1.6 years (with the initial course of radiation therapy being given with conventional prescription doses of ≤2 Gy per fraction and the second course with variable fractionations). We recommend a uniform approach for reporting dosimetric endpoints to derive robust predictive models of late toxicities following reirradiation. #radiationoncology #radonc #radiotherapy #oncology #SNC #nerulogy #pediatrics #cancer #pediatriccancer https://lnkd.in/diFR5wtg

Pediatric intestinal pseudo-obstruction (PIPO) is a rare congenital disorder of the enteric nervous system with distal colon aganglionosis potentially leading to intestinal obstruction. Recently, biallelic variants in KIF26A, encoding a crucial motor protein for the migration and differentiation of enteric neural crest cells, have been associated with a neurodevelopmental condition featuring cortical defects and PIPO-like features, though in absence of aganglionosis. So far, only 10 patients have been reported. In this study, we investigated three subjects with congenital hydrocephalus, neurodevelopmental impairment, and intestinal obstruction megacolon syndrome. Brain MRI revealed malformations within cortical dysplasia spectrum, including polymicrogyria and heterotopia. Pathology study of the intestine revealed aganglionosis and elevated acetylcholinesterase activity in parasympathetic nerve fibers. Through trio-exome sequencing (ES), we detected four novel biallelic KIF26A variants, including two missense changes (#1) and two distinct homozygous truncating variants in (#2 and #3). All variants are rare and predicted to be deleterious according to in silico tools. To characterize the impact of the missense variants, we performed 3D protein modeling using Alphafold3 and YASARA. Mutants exhibited increased energy scores compared to wild-type protein, supporting a significant structural destabilization of the protein. Our study expands the genotype and phenotype spectrum of the emerging KIF26A-related disorder.

Key takeaways: Transvaginal ultrasonography below 5 mm led to misclassification of Black women with endometrial cancer; more than one in 10 Black women, suggesting it is not a reliable strategy to identify Black women at risk for endometrial cancer. Transvaginal ultrasonography below 5 mm led to misclassification of Black women with endometrial cancer. A previous simulation study using population estimates suggested that the transvaginal ultrasonography triage approach may miss cases of endometrial cancer among Black individuals due to their greater prevalence of fibroids and nonendometrioid histologic types,” Kemi M. Doll, MD, MSCR, gynecologic oncologist in the department of obstetrics and gynecology at the Fred Hutchinson Cancer Center at the University of Washington, and colleagues wrote in JAMA Oncology. Doll and colleagues conducted a retrospective diagnostic study using merged abstracted electronic health record data and secondary administrative data from 1,494 Black women (median age, 46.1 years) from the GUIDE-EC sample. Primary outcomes included ultrasonography performed before hysterectomy, demographic and clinical data on symptom presentation, endometrial characterization and final endometrial cancer diagnosis. Overall, 210 women had endometrial cancer. The most common presenting diagnoses within 30 days of vaginal ultrasonography were fibroids (78.1%), vaginal bleeding (71.4%) and pelvic pain (57.4%). False-negative probabilities were 3.8% with the 3 mm endometrial thickness threshold, 9.5% with the 4 mm threshold and 11.4% with the 5 mm threshold. Endometrial cancer risk factors had similar false-negative probabilities at the 5 mm threshold, with 12.4% for postmenopausal bleeding, 9.3% for BMI greater than 40 kg/m2 and 12.8% for age 50 years or older. False-negative probabilities for Black women with fibroids identified via pelvic ultrasonography ranged from 4.4% with the 3 mm threshold to 11.8% in the 5 mm threshold. Black women with partially visible endometrial thickness and/or pelvic pain had higher false-negative probabilities with 3 mm and 5 mm thresholds, ranging from 13% to 26.1% and 4.8% to 14.5%, respectively. “These findings suggest that the transvaginal ultrasonography triage strategy is not reliable among Black adults at risk for endometrial cancer,” the researchers wrote. “In the presence of postmenopausal bleeding, tissue sampling is strongly recommended.” Source: Doll KM, et al. JAMA Oncol. 2024;doi:10.1001/jamaoncol.2024.1891. Disclosures: Doll reports receiving investigator-initiated research grants from the American Association of Cancer Research, Merck and the Patient-Centered Outcomes Research Institute. Please see the study for all other authors’ relevant financial disclosures

#AI Screening of #Pediatric Cancers Improves #Treatment Outcomes AI-powered, functional precision medicine platform used to identify unique therapeutic treatment options in pediatric #cancer. #consultants #artificialintelligence #decisionmaking #bigdata #DataScience #web3 #machinelearning #future #technology #cloud #DataAnalytics #LinkedIn #innovation #Business #Sales #creativity #futurism #AIhealth #healthcare

Muscular Dystrophy Online Course: Paediatric Conditions – Down Syndrome, Duchenne Muscular Dystrophy, Osteogenesis Imperfecta and Arthrogryposis Introduction Muscular dystrophy refers to a group of hereditary disorders that cause progressive, generalised muscle weakness and atrophy. Muscular dystrophy is a non-communicable disorder and has many variations - each variation has a specific inheritance pattern, time of onset and rate of muscle loss.[1] Aetiology In most cases, muscular dystrophy is caused by absent or defective glycoproteins in the muscle membrane. In each type of muscular dystrophy, different genes are deleted or mutated. These changes can impact various enzymatic or metabolic functions. The gene that causes Duchenne muscular dystrophy was discovered in 1986.[2] The muscle protein associated with this gene was named "dystrophin".[3] Dystrophin forms an integral part of a muscle's cytoskeleton - it links the contractile apparatus to the sarcolemma. "Absence or reduced expression of dystrophin or many of the [dystrophin protein complex] components cause the muscular dystrophies."[3] MuscularDystrophy.png The image on the right shows muscle tissue in an individual with muscular dystrophy. The tissue in this image is disorganised, and there is a reduced concentration of dystrophin (the area shown in green).[4] The dystrophin gene is the largest gene in the human genome.[1] Because of its large size, it is prone to high rates of spontaneous mutations.[1] Duchenne muscular dystrophy (DMD) occurs when the dystrophin gene stops making dystrophin.[2] Becker muscular dystrophy is associated with a different mutation on the dystrophin gene, causing it to no longer make enough dystrophin (or the quality is low).[2] Most muscular dystrophies are X-linked recessive disorders, so muscular dystrophy is more common in biological males.[2][5] Epidemiology Overall prevalence:[6] Muscular Dystrophy: 3.6 per 100,000 people Duchenne Muscular Dystrophy: 4.6 per 100,000 people Becker Muscular Dystrophy: 1.6 per 100,000 people The highest prevalence is in the Americas, with 5.1 per 100,000 people. The lowest prevalence is in Africa, with 1.7 per 100,000.[6] ManagementWheelchair child.jpg There is no cure for muscular dystrophy, but appropriate treatment can help manage symptoms and improve quality of life. 1. Medical interventions include:[1] anti-arrhythmic drugs anti-epileptic drugs anti-myotonic drugs non-steroidal anti-inflammatory drugs (NSAIDs) steroids 2. Surgical interventions include:[1] placement of defibrillator or pacemaker release of contractures spinal correction 3. Other interventions can include:[1] supportive physiotherapy supportive bracing supportive counselling genetic counselling #snsinstitutions #snsdesignthinkers #snsdesignthinking

China has successfully completed ovarian tissue #cryopreservation and transplantation to help women who lost ovarian function because of tumor treatments and hematopoietic stem cell transplantation, also known as bone marrow transplant, preserve their fertility. To learn more: https://lnkd.in/dhdw5-4g #TissueCryopreservation #OvarianTissue #Preservation #Biobank #Biobanking #Biorepository #Fertility #Cancer #Oncology #Transplantation #FertilityPreservation