Lynch syndrome (LS) is the most common hereditary colon cancer syndrome caused by germline mutations in mismatch repair (MMR) genes. In this series, we outline 3 pediatric patients who presented with vague symptoms due to colorectal cancer who were eventually diagnosed with Lynch syndrome with multiple gene mutations. The diagnosis of colorectal cancer in pediatrics warrants timely recognition, inclusion of Lynch syndrome in the differential diagnosis, multi-gene testing, and genetic counseling for the patient and family.
Spatial and temporal heterogeneity, or messiness, is a broadly desirable characteristic of river corridors and an indicator of many of the geomorphic processes that sustain fluvial ecosystems. However, quantifying geomorphic heterogeneity is complicated by a lack of consistent metrics, classification schemas for dividing the river corridor into the patches that form the basis for those metrics, and guidance on interpreting metrics. Drawing from both geomorphic and landscape ecology concepts, we offer ideas and guidance intended to help investigators, from researchers to restoration practitioners, more effectively and reliably use heterogeneity to describe river corridor processes and characteristics. We define geomorphic heterogeneity both spatially and temporally. Spatially, heterogeneity can be described by diversity, or the evenness and richness of geomorphic units, and spatial configuration, or the arrangement and shape of geomorphic units. Temporally, heterogeneity can be described by turnover rate, or the rate of change of geomorphic units. Interpretation of heterogeneity metrics depends integrally on the definition of the geomorphic unit schema on which metrics are based. Contextual information, such as measurements of process space (i.e., how much room a river has to move), disturbance frequency, and geomorphic trajectory, can also be key to interpreting measurements of heterogeneity. Geomorphic applications of heterogeneity require carefully defined geomorphic unit schemas that reflect processes and characteristics of interest, robust metrics of heterogeneity whose meaning is appropriate to the question at hand, and interpretation of those metrics based on the context of expected geomorphic processes and the disturbance regime.
We experienced the case of a patient with advanced breast cancer who failed to receive comprehensive care despite regular video conferencing with her physician during the COVID-19 pandemic, resulting in delayed detection of liver metastasis. Inter-hospital collaboration is required to provide uninterrupted cancer care to those disproportionately affected by crises.
In total arch replacement, using frozen elephant trunk (FET) or elephant trunk techniques ensures proximalization of the distal anastomosis. However, in some cases, the left subclavian artery (LSCA) is deeply located and difficult to visualize. Therefore, surgeons face technical challenges during the LSCA reconstruction. We report an end-to-side anastomosis technique that enables safer and easier anatomical reconstruction of the LSCA.
Eruptive xanthomas are skin manifestations associated with hypertriglyceridemia. Accordingly, improvement of hypertriglyceridemia can ameliorate this condition. We report a case of a patient with type 2 diabetes mellitus who was diagnosed with this skin lesion. Clinicians should be aware that eruptive xanthomas could indicate metabolic disorders associated with atherosclerosis.
Aims: To update our previously reported systematic review and meta-analysis of observational studies on cardiovascular drug exposure and COVID-19 clinical outcomes by focusing on newly published randomized controlled trials (RCTs). Methods: More than 500 databases were searched between 1-Nov-2020 and 2-Oct-2021 to identify RCTs that were published after our baseline review. One reviewer extracted data with other reviewers verifying the extracted data for accuracy and completeness. Results: After screening 22,414 records, we included 24 and 21 RCTs in the qualitative and quantitative syntheses, respectively. The most investigated drug classes were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARBs) and anticoagulants, investigated by 10 and 11 studies respectively. In meta-analyses, ACEI/ARBs did not affect hospitalization length (mean difference/MD -0.42, 95% CI -1.83; 0.98 days, n=1183), COVID-19 severity (risk ratio/RR 0.90, 95% CI 0.71; 1.15, n=1661) and mortality (RR 0.92, 95% CI 0.58; 1.47, n=1646). Therapeutic anticoagulation also had no effect (hospitalization length MD -0.29, 95% CI -1.13 to 0.56 days, n=1449; severity RR 0.86, 95% CI 0.70;1.04, n=2696; and, mortality RR 0.93, 95% CI 0.77;1.13, n=5689). Other investigated drug classes were antiplatelets (aspirin, 2 trials), antithrombotics (sulodexide, 1 trial), calcium channel blockers (amlodipine, 1 trial) and lipid modifying drugs (atorvastatin, 1 trial). Conclusion: Moderate- to high-certainty RCT evidence suggests that cardiovascular drugs such as ACEIs/ARBs are not associated with poor COVID-19 outcomes, and should therefore not be discontinued. These cardiovascular drugs should also not be initiated to treat or prevent COVID-19 unless they are needed for an underlying currently approved therapeutic indication.
In patients with inherited bleeding disorders, thrombus development poses a challenge in balancing the management of thrombosis and bleeding. Pediatric antithrombotic therapy guidelines do not address the treatment of a thrombus in the setting of a bleeding disorder. We present a case series of four children with inherited bleeding disorders presenting with cerebral sinus venous thrombosis and bleeding, in order to summarize the different therapeutic approaches and outcomes of these patients.
Background The incidence of thyroid cancer is increasing globally due to the increase in detection of subclinical, low volume papillary thyroid microcarcinomas (PTMC) (<1cm). Several international groups have recommended an active surveillance approach for this low-risk disease. In contrast to many other countries, the UK’s approach to thyroid nodules is to avoid detection of incidental lesions where appropriate. Objective This study aims to establish the proportion of patients with thyroid cancer in the UK that would benefit from active surveillance. Design, participants, and outcome measures: Individuals with PTMC in NHS Lothian from 2009-2020 were reviewed from a local thyroid cancer database. The mode of detection of PTMC and proportion of patients who might benefit from active surveillance were established. Results From 651 individuals with differentiated thyroid cancer managed over 12-year period, 185 individuals with PTMC were identified (28.4%). The majority of PTMC 151/185 (81.6%) were either diagnosed post-operatively following thyroidectomy for benign disease or with nodal disease. Only 24 individuals with PTMC were identified following palpable thyroid nodule, incidental finding on imaging and surveillance screening. Therefore, when the indication for surgery was considered, only 24/651 (3.7%) patients were identified pre-operatively and would therefore be realistic candidates for active surveillance. Conclusion Less than 4% of patients with thyroid cancer in the UK would be appropriate for active surveillance. Rather than developing programs to deal with this minority of patients, focus should be maintained on minimizing detection of these low-risk cases.
Introduction: A large proportion of patients with infectious mononucleosis (IM) have abnormal liver function tests (LFT) at presentation. There is no guideline regarding the management and follow-up of these patients. Some patients also have abdominal ultrasound due to deranged LFT, the need for this practice is unclear. The aim of this systematic review was to evaluate the evidence base on LFT assessment in IM, time to resolution of derangement, and the role of abdominal ultrasound. Methods: A systematic search of PubMed, EMBASE and the Cochrane library was done. Two authors independently screened records for eligibility using pre-defined criteria. We included both adult and paediatric populations. Quality assessment of included studies was done. Results: A total of 3924 patients were included from 32 studies. A combination of typical clinical features, heterophile antibodies and EBV-specific antibodies were used to ascertain diagnosis. The following proportion of patients had abnormal LFTs: AST (57%); ALT (62%); ALP (65%); Bilirubin (16%); GGT (41%). Reported median (i.q.r.) time to resolution of LFT was 8 (6–12) weeks. Maximum time to resolution was >6 months. Clinical hepatomegaly and splenomegaly were found in 35% and 44% of patients respectively. Enlarged liver and spleen on ultrasound were seen in 16/29 (55%) and 38/38 (100%) of patients respectively. There were no reports of decompensated liver disease. Conclusion: Derangement in LFTs can persist over six months from initial presentation in IM. However, this is self-limiting. The evidence suggests serial liver function assessments and ultrasound abdomen are not required in immunocompetent patients with subclinical derangement in LFTs.
The term “haplotype block” is commonly used in the developing field of haplotype-based inference methods. We argue that the term should be defined based on the structure of the Ancestral Recombination Graph (ARG), which contains complete information on the ancestry of a sample. We use simulated examples to demonstrate key features of the relation between haplotype blocks and ancestral structure, emphasising the stochasticity of the processes that generate them. Even the simplest cases of neutrality or of a “hard” selective sweep produce a rich structure, often missed by commonly used statistics. We highlight a number of novel methods for inferring haplotype structure, based on the full ARG, or on a sequence of trees, and illustrate how they can be used to define haplotype blocks using an empirical dataset. While the arrival of computationally efficient methods makes it possible to apply these concepts broadly, existing and new methods could include tools for the identification and explore haplotype blocks, as we define them. Understanding and applying the concept of the haplotype block will be essential to fully exploit long and linked-read sequencing technologies.
Synteny, the ordering of sequences within homologous chromosomes, must be maintained within the genomes of sexually reproducing species for the sharing of alleles and production of viable, reproducing offspring. However, when the genomes of closely related species are compared, a loss of synteny can be observed. Synteny loss may be occurring due to transposon-mediated recombination errors during meiosis, unequal homologous recombination, resulting in the formation of chromosomal rearrangements. To examine patterns of synteny amongst three closely related, interbreeding, and wild Eucalyptus species, we assembled their genomes using long-read DNA sequencing and de novo assembly. We identify syntenic and rearranged regions between these genomes and estimate that ~48% of our genomes remain syntenic while ~36% is rearranged. We observed that rearrangements highly fragment micro-synteny, however genome-wide, macro-synteny appears to be maintained. Our results suggest that synteny between our species is primarily lost through small-scale rearrangements, not through sequence loss, gain, or sequence divergence. Further examination of identified rearrangements suggests that rearrangements may be altering the phenotypes of Eucalyptus species. Our study also questions the use of single reference genomes in genomic studies, reliance on a single reference genome when seeking genetic variation leads to reference bias, especially given the scale at which we show potentially adaptive loci have highly diverged, deleted, duplicated and/or rearranged. This study provides an unbiased framework to look at potential speciation and adaptive loci among a rapidly radiating foundation species of woodland trees that are free from selective breeding seen in most crop species.