Presentation of B-cell lymphoma in childhood and adolescence: a systematic review and meta-analysis

Background: The diagnosis of B-cell lymphoma, one of the commonest cancers seen in childhood and adolescence, is challenging. There is a crucial need to identify and delineate the prevalence of associated symptoms in order to improve early diagnosis. Aims: To identify clinical presentations associated with childhood and adolescent B-cell lymphomas and estimate symptom prevalence. Methods: A systematic review of observational studies and meta-analysis of proportions was carried out. Medline and EMBASE were systematically searched, with no language restrictions, from inception to 1st August 2022. Observational studies with at least 10 participants, exploring clinical presentations of any childhood and adolescent lymphoma, were selected. Proportions from each study were inputted to determine the weighted average (pooled) proportion, through random-effects meta-analysis. Results: Studies reported on symptoms, signs and presentation sites at diagnosis of 12,207 children and adolescents up to the age of 20. Hodgkin’s lymphoma most frequently presented with adenopathy in the head-and-neck region (79% [95% CI 58%-91%]), whilst non-Hodgkin’s lymphoma presented abdominally (55% [95% CI 43%-68%]). Symptoms associated with lymphoma included cervical lymphadenopathy (48% [95% CI 20%-77%]), peripheral lymphadenopathy (51% [95% CI 37%-66%]), B-symptoms (40% [95% CI 34%-44%]), fever (43% [95% CI 34%-54%]), abdominal mass (46% [95% CI 29%-64%]), weight loss (53% [95% CI 39%-66%]), head-and-neck mass (21% [95% CI 6%-47%]), organomegaly (29% [95% CI 23%-37%]), night sweats (19% [95% CI 10%-32%]), abdominal pain (28% [95% CI 15%-47%]), bone pain (17% [95% CI 10%-28%]) and abnormal neurology (11% [95% CI 3%-28%]). Conclusion: This systematic review and meta-analysis of proportions provides insight into the heterogeneous clinical presentations of B-cell lymphoma in childhood and adolescence and provides estimates of symptom prevalence. This information is likely to increase public and clinical awareness of lymphoma presentations and aid earlier diagnosis. This review further highlights the lack of studies exploring childhood and adolescent lymphoma presentations in primary care, where patients are likely to present at the earliest stages of their disease

Investigations of spinodal dynamics in asymmetric nuclear matter within a stochastic relativistic model

Cataloged from PDF version of article.Early development of spinodal instabilities and density correlation functions in asymmetric nuclear matter are investigated in the stochastic extension of the Walecka-type relativistic mean field including coupling with rho meson. Calculations are performed under typical conditions encountered in heavy-ion collisions and in the crusts of neutron stars. In general, growth of instabilities occur relatively slower for increasing charge asymmetry of matter. At higher densities around rho = 0.4 rho(0) fluctuations grow relatively faster in the quantal description than those found in the semi-classical limit. Typical sizes of early condensation regions extracted from density correlation functions are consistent with those found from dispersion relations of the unstable collective modes

Dexamethasone Implant (Ozurdex) in a Case with Unilateral Simultaneous Central Retinal Vein and Branch Retinal Artery Occlusion

Simultaneous branch retinal artery and vein occlusion is a rare condition that may cause severe visual loss, and its treatment is often unrewarding. Herein, we report a case with simultaneous central retinal vein and branch retinal artery occlusion; it was successfully treated with a single dexamethasone intravitreal implant. The affected eye attained a visual acuity level of 20/25 from the visual acuity of hand motions at presentation with a residual, but relatively diminished, altitudinal scotoma during a follow-up period of 6 months

Abdominal migraine

Abdominal migraine is an important, common, and under-recognised cause of recurrent abdominal pain in children. It may be associated with, or followed by, other forms of migraine, and it predicts adult migraine.1234A positive diagnosis of abdominal migraine allows appropriate management and avoids unnecessary investigations and incorrect treatments.35 Although the evidence base is limited, acute and preventive treatments are available. This article highlights the diagnosis and management of abdominal migraine for non-specialists

Bilateral Intravitreal Ranibizumab Injection and Panretinal Photocoagulation in a 16-Year-Old Girl with Severe Vaso-Occlusive Lupus Retinopathy

A 16-year-old girl with fever of unknown origin and bilateral vaso-occlusive retinopathy with retinal neovascularization, preretinal hemorrhage, and serous macular detachment was treated with single bilateral 0.5 mg intravitreal ranibizumab injection prior to aggressive PRP with success. No systemic steroids or immunosuppressive therapy was employed at that time. She received the diagnosis of “systemic lupus erythematosus” five years after this episode with further systemic symptoms. In certain cases with vaso-occlusive type of lupus retinopathy, anti-VEGF agents may be administered in addition to panretinal photocoagulation to achieve better visual and anatomic outcome

Bilateral Severe Sterile Inflammation with Hypopyon after Simultaneous Intravitreal Triamcinolone Acetonide and Aflibercept Injection in a Patient with Bilateral Marked Rubeosis Associated with Ocular Ischemic Syndrome

We report the clinical course of a diabetic patient with bilateral cataract and rubeosis in association with ocular ischemic syndrome and initially treated him with simultaneous intravitreal 2 mg aflibercept and 2 mg triamcinolone acetonide injection at the same setting prior to planned cataract surgery and further photocoagulation. However, sterile anterior segment inflammation characterized by hypopyon occurred four days apart in OU. Right eye developed the sterile inflammation at the third postinjection day and the left eye developed the sterile inflammation at the seventh postinjection day (two days after the uneventful cataract surgery with intraocular lens implantation) without any pain or significant redness. Vitreous biopsy taken during the right phacovitrectomy was negative for any microbial contamination. Both eyes were treated successfully with intensive topical prednisolone acetate with a relatively good visual outcome. It is likely that underlying ocular ischemic syndrome might have facilitated the formation of sterile inflammation as blood-aqueous barrier disruption and flare have already been present

Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study.

ObjectiveTo assess the association between covid-19 vaccines and risk of thrombocytopenia and thromboembolic events in England among adults.DesignSelf-controlled case series study using national data on covid-19 vaccination and hospital admissions.SettingPatient level data were obtained for approximately 30 million people vaccinated in England between 1 December 2020 and 24 April 2021. Electronic health records were linked with death data from the Office for National Statistics, SARS-CoV-2 positive test data, and hospital admission data from the United Kingdom's health service (NHS).Participants29 121 633 people were vaccinated with first doses (19 608 008 with Oxford-AstraZeneca (ChAdOx1 nCoV-19) and 9 513 625 with Pfizer-BioNTech (BNT162b2 mRNA)) and 1 758 095 people had a positive SARS-CoV-2 test. People aged ≥16 years who had first doses of the ChAdOx1 nCoV-19 or BNT162b2 mRNA vaccines and any outcome of interest were included in the study.Main outcome measuresThe primary outcomes were hospital admission or death associated with thrombocytopenia, venous thromboembolism, and arterial thromboembolism within 28 days of three exposures: first dose of the ChAdOx1 nCoV-19 vaccine; first dose of the BNT162b2 mRNA vaccine; and a SARS-CoV-2 positive test. Secondary outcomes were subsets of the primary outcomes: cerebral venous sinus thrombosis (CVST), ischaemic stroke, myocardial infarction, and other rare arterial thrombotic events.ResultsThe study found increased risk of thrombocytopenia after ChAdOx1 nCoV-19 vaccination (incidence rate ratio 1.33, 95% confidence interval 1.19 to 1.47 at 8-14 days) and after a positive SARS-CoV-2 test (5.27, 4.34 to 6.40 at 8-14 days); increased risk of venous thromboembolism after ChAdOx1 nCoV-19 vaccination (1.10, 1.02 to 1.18 at 8-14 days) and after SARS-CoV-2 infection (13.86, 12.76 to 15.05 at 8-14 days); and increased risk of arterial thromboembolism after BNT162b2 mRNA vaccination (1.06, 1.01 to 1.10 at 15-21 days) and after SARS-CoV-2 infection (2.02, 1.82 to 2.24 at 15-21 days). Secondary analyses found increased risk of CVST after ChAdOx1 nCoV-19 vaccination (4.01, 2.08 to 7.71 at 8-14 days), after BNT162b2 mRNA vaccination (3.58, 1.39 to 9.27 at 15-21 days), and after a positive SARS-CoV-2 test; increased risk of ischaemic stroke after BNT162b2 mRNA vaccination (1.12, 1.04 to 1.20 at 15-21 days) and after a positive SARS-CoV-2 test; and increased risk of other rare arterial thrombotic events after ChAdOx1 nCoV-19 vaccination (1.21, 1.02 to 1.43 at 8-14 days) and after a positive SARS-CoV-2 test.ConclusionIncreased risks of haematological and vascular events that led to hospital admission or death were observed for short time intervals after first doses of the ChAdOx1 nCoV-19 and BNT162b2 mRNA vaccines. The risks of most of these events were substantially higher and more prolonged after SARS-CoV-2 infection than after vaccination in the same population

Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection

Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280). There was an increased risk of Guillain–Barré syndrome (incidence rate ratio (IRR), 2.90; 95% confidence interval (CI): 2.15–3.92 at 15–21 days after vaccination) and Bell’s palsy (IRR, 1.29; 95% CI: 1.08–1.56 at 15–21 days) with ChAdOx1nCoV-19. There was an increased risk of hemorrhagic stroke (IRR, 1.38; 95% CI: 1.12–1.71 at 15–21 days) with BNT162b2. An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain–Barré syndrome (IRR, 2.32; 95% CI: 1.08–5.02 at 1–28 days). There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain–Barré syndrome (IRR, 5.25; 95% CI: 3.00–9.18). Overall, we estimated 38 excess cases of Guillain–Barré syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test. In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test

spot 003 thymidylate synthase maintains the undifferentiated state of aggressive breast cancers

Introduction De-differentiation is a highly lethal feature of aggressive breast cancers (BC), and is achieved through the epithelial-to-mesenchymal transition (EMT) and the cancer stem cell (CSC) programs. Targeting the mechanisms controlling BC de-differentiation can lead to more effective therapeutics. Recent studies indicated that nucleotide metabolism can regulate cancer stemness and EMT. Here we investigated the expression of the nucleotide metabolism enzyme and drug target thymidylate synthase (TS) in the BC subtypes and analysed its impact on BC de-differentiation. Material and methods Cells with TS knockdown and overexpression were tested in vitro and in vivo. Proteins were analysed by western blot, FACS and ELISA. Differential gene expression in TS-deficient cells was determined by RNA-seq. Immunohistochemistry (IHC) was used to stain samples from patients with different BC subtypes. Results and discussions TS mRNA expression was found to be significantly differentially expressed among the BC subtypes, exhibiting the highest levels in aggressive triple-negative BC (TNBC). shRNA-mediated TS knockdown in TNBC cell lines (n=3) increased the population of differentiated cells (CD24high) and strongly attenuated the stem-like phenotype, like the formation of mammospheres from single cells and the migration in a cell culture wound. TS-deficient cells also showed an altered ability to form metastasis in vivo, consistent with previous observations in EMT-repressed BC cells. A rescue experiment performed by overexpressing either a wild-type or catalytically inactive TS indicated that the enzymatic activity was essential for the maintenance of the BCSC phenotype. Along with a strong repression of EMT-signature genes, RNA-seq profiling indicated a reduction of inflammatory and NF-κB signalling pathways in TS deficient cells, which dramatically reduced IL-1β production and secretion. A TS-specific gene signature was generated, which significantly associated with worst survival in BC patients. IHC staining on FFPE samples from a series of BC patients (n=120) confirmed higher TS expression in tumours that were poorly differentiated and in TNBC. Conclusion We discovered a novel role for the TS enzyme in the maintenance of a de-differentiated and stem-like state of BC. These findings may not only open the possibility to study in-depth the role of nucleotide metabolism at the crossroad between proliferation and differentiation, but may provide the rationale for novel drug combinations with TS-inhibiting agents for the treatment of BC