Presence of lung metastases in low-risk gestational trophoblastic neoplasia (GTN) is generally considered not to influence prognosis. However, in a recent study in the Netherlands, GTN patients with lung metastases had a higher recurrence rate and more disease-specific deaths compared with patients without metastases. The aim of the present study was to validate these findings in a different country.Historical cohort study.Charing Cross Hospital, United Kingdom.A total of 1040 low-risk GTN patients treated with methotrexate (MTX) between 2002 and 2016 were identified: 65 with lung metastases (group 1) and 975 without metastases (group 2).Baseline characteristics, MTX resistance, survival and recurrence rates were recorded and compared between both groups.MTX resistance, recurrence rate and survival.The occurrence of MTX resistance and median number of MTX courses to achieve remission was significantly higher in patients with lung metastases than patients without metastases (60% versus 38.9%, P = 0.001; and nine versus six courses, P < 0.001). All choriocarcinoma patients (n = 4) with lung metastases developed MTX resistance. The recurrence rate was also higher in group I (9.2% versus 2.7%; P = 0.012). Disease-specific survival was 100% in both groups.The presence of lung metastases at the start of MTX therapy is associated with increased incidence of MTX resistance and recurrence in low-risk GTN without affecting overall survival, which remains 100%. However, individuals with low-risk choriocarcinoma with lung metastases are likely to become resistant to MTX and primary multi-agent chemotherapy should be considered.The presence of lung metastases appears to increase the risk of recurrence in low-risk GTN, but does not affect overall cure rates and survival.
"Massive perivillous fibrin deposition associated with discordant fetal growth in a dichorionic twin pregnancy." Journal of Obstetrics and Gynaecology, 24(5), pp. 579–580
Background: Proteus Syndrome is a rare, sporadic overgrowth disorder for which the underlying genetic defect remains unknown. Although the clinical course is well-described, there is no systematic histopathological description of the lesional pathology. Objective: To describe the histopathological features encountered in a series of patients with Proteus syndrome from a single centre. Patients/Methods: Patients with Proteus syndrome who had undergone therapeutic surgical resection or biopsy were identified from a database and the histopathological findings were reviewed, with particular reference to descriptive features of the underlying tissue abnormality. Results: There were 18 surgical specimens from nine patients, median age 4 (range 1–9) years, including four main categories; soft tissue swellings (lipomatous lesions), vascular anomalies (vascular malformation and haeman-gioma), macrodactyly (hamartomatous overgrowth) and others (sebaceous naevus and non-specific features). In all cases the clinical features of overgrowth were due to increased amounts of disorganised tissue, indicating a hamartomatous-type defect in which normal tissue constituents were present but with an abnormal distribution and architecture. Vascular malformations represented a prominent category of lesions, accounting for 50% of the specimens, predominantly comprising lymphatic and lymphovascular malformations. No malignancy or cytological atypia was identified in any case. Conclusions: The histopathological features of lesions resected from children with Proteus syndrome predominantly include hamartomatous mixed connective tissue lesions, benign neoplasms such as lipomata and lymphatic-rich vascular malformations.
Background Pregnant women have been identified as a potentially at‐risk group concerning COVID‐19 infection, but little is known regarding the susceptibility of the fetus to infection. Co‐expression of ACE2 and TMPRSS2 has been identified as a prerequisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown. Methods We performed a retrospective analysis of a single cell data repository. The data were then validated at both gene and protein level by performing RT‐qPCR and two‐colour immunohistochemistry on a library of second‐trimester human fetal tissues. Findings TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels only in the fetal intestine and kidney, and is not expressed in the fetal lung. The placenta also does not co‐express the two proteins across the second trimester or at term. Interpretation This dataset indicates that the lungs are unlikely to be a viable route of SARS‐CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the gastrointestinal tract is likely to be susceptible to infection due to its high co‐expression of both proteins, as well as its exposure to potentially infected amniotic fluid. Tweetable abstract This work provides detailed mechanistic insight into the relative protection & vulnerabilities of the fetus & placenta to SARS‐CoV‐2 infection by scRNAseq & protein expression analysis for ACE2 & TMPRSS2. The findings help to explain the low rate of vertical transmission.
Inflammatory linear verrucous epidermal nevus should be genotyped to direct treatment and genetic counselingTo the Editor: Inflammatory linear verrucous epidermal nevus (ILVEN) is a clinical diagnosis based on persistent Blaschko-linear erythematous scaly and usually pruritic lesions.Sixteen patients with a clinical diagnosis of ILVEN as defined by published diagnostic criteria were recruited and consented under Research Ethics Committee approval for phenotypic, histological, and genotypic analysis.At the time of initiating this study in 2014 no genetic causes of ILVEN were known.Causative genetic variants since described are in GJA1, 1 ABCA12 2 , CARD14, 3 PMVK 4 , NSDHL, 4 HRAS 4 and KRT10. 4Disease mechanisms thus far include germline X-linked variants, mosaic variants, and germline first hit with mosaic second hit.Paired blood and affected skin DNA underwent deep whole exome sequencing (WES, mean 250X), n ¼ 14, and if negative, skin DNA underwent targeted sequencing panel R327 (mosaic disorders, UK National Genomic Test Directory), n ¼ 8. Two patients had a negative WES and did not go forward to next generation sequencing panel due to sample limitations.Two patients recruited late in the study had next generation sequencing panel first and did not proceed to WES.We confirm here that ILVEN has multiple monogenic causes, with mutations in NSDHL (n ¼ 2, germline, NSDHL c.613G [ T, p.[G205T ], c.603_604delTG, p.[H201fs*69], both picked up on WES), PMVK (n ¼ 1, mosaic in blood and skin, no second variant detected in the same gene in skin, PMVK c.126delG, p.R42fs, picked up on WES), HRAS (n ¼ 1, mosaic, HRAS c.37G [ C, p.(G13R), picked up on panel, and CARD14 (n ¼ 2, mosaic, these 2 only previously published, 1 both picked up on WES).Ten patients had no pathogenic variants identified and we specifically excluded any variants in all previously described genes.No patients who were negative on WES had genes identified on a subsequent panel, suggesting that variants still unidentified are not in known mosaic genes, or if they are they are unlikely to be
UNSTRUCTURED The cognitive load theory suggests that completing a task relies on the interplay between sensory input, working memory, and long-term memory. Cognitive overload occurs when the working memory’s limited capacity is exceeded due to excessive information processing. In health care, clinicians face increasing cognitive load as the complexity of patient care has risen, leading to potential burnout. Electronic health records (EHRs) have become a common feature in modern health care, offering improved access to data and the ability to provide better patient care. They have been added to the electronic ecosystem alongside emails and other resources, such as guidelines and literature searches. Concerns have arisen in recent years that despite many benefits, the use of EHRs may lead to cognitive overload, which can impact the performance and well-being of clinicians. We aimed to review the impact of EHR use on cognitive load and how it correlates with physician burnout. Additionally, we wanted to identify potential strategies recommended in the literature that could be implemented to decrease the cognitive burden associated with the use of EHRs, with the goal of reducing clinician burnout. Using a comprehensive literature review on the topic, we have explored the link between EHR use, cognitive load, and burnout among health care professionals. We have also noted key factors that can help reduce EHR-related cognitive load, which may help reduce clinician burnout. The research findings suggest that inadequate efforts to present large amounts of clinical data to users in a manner that allows the user to control the cognitive burden in the EHR and the complexity of the user interfaces, thus adding more “work” to tasks, can lead to cognitive overload and burnout; this calls for strategies to mitigate these effects. Several factors, such as the presentation of information in the EHR, the specialty, the health care setting, and the time spent completing documentation and navigating systems, can contribute to this excess cognitive load and result in burnout. Potential strategies to mitigate this might include improving user interfaces, streamlining information, and reducing documentation burden requirements for clinicians. New technologies may facilitate these strategies. The review highlights the importance of addressing cognitive overload as one of the unintended consequences of EHR adoption and potential strategies for mitigation, identifying gaps in the current literature that require further exploration.
To determine the utility of pre-implantation renal biopsy (PIB) to predict renal allograft outcomes.This is a retrospective review of all patients that underwent PIB from January 2003 to December 2011 at the Great Ormond Street Hospital for Children in London, United Kingdom. Thirty-two male patients (56%) aged 1.5-16 years (median: 10.2) at the time of transplantation were included in the study and followed-up for 33 (6-78) months. The results were compared with 33 controls.The PIB showed normal histopathological findings in 13 patients (41%), mild chronic vascular changes in 8 (25%), focal tubular atrophy in one, moderate to severe chronic vascular change in 3, mild to moderate acute tubular damage in 6, and tissue was inadequate in one subject. Delayed graft function (DGF) was observed in 3 patients; 2 with vascular changes in PIB, and one with normal histopathological findings. Two subjects with PIB changes lost their grafts. The estimated glomerular filtration rate at 3-, and 6-months post-transplantation was lower in children with abnormal PIB changes compared with those with normal PIB. There was one case of DGF in the control group, and 4 children lost their grafts including the one with DGF.Pre-implantation renal biopsy can provide important baseline information of the graft with implications on subsequent medical treatment for pediatric renal transplant recipients.
Renal ciliopathies are a group of genetic disorders that affect the function of the primary cilium in the kidney, as well as other organs. Since primary cilia are important for regulation of cell signaling pathways, ciliary dysfunction results in a range of clinical manifestations, including renal failure, cyst formation, and hypertension. We summarize the current understanding of the pathophysiological and pathological features of renal ciliopathies in childhood, including autosomal dominant and recessive polycystic kidney disease, nephronophthisis, and Bardet-Biedl syndrome, as well as skeletal dysplasia associated renal ciliopathies. The genetic basis of these disorders is now well-established in many cases, with mutations in a large number of cilia-related genes such as
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