Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 179
Filtrar
1.
Exp Physiol ; 109(2): 214-226, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38050866

RESUMO

Autonomic dysfunction is a common complication of type 2 diabetes mellitus (T2DM). However, the character of dysfunction varies in different reports. Differences in measurement methodology and complications might have influenced the inconsistent results. We sought to evaluate comprehensively the relationship between abnormal glucose metabolism and autonomic function at rest and the response to exercise in healthy individuals and T2DM patients. We hypothesized that both sympathetic and parasympathetic indices would decrease with the progression of abnormal glucose metabolism in individuals with few complications related to high sympathetic tone. Twenty healthy individuals and 11 T2DM patients without clinically evident cardiovascular disease other than controlled hypertension were examined. Resting muscle sympathetic nerve activity (MSNA), heart rate variability, spontaneous cardiovagal baroreflex sensitivity (CBRS), sympathetic baroreflex sensitivity and the MSNA response to handgrip exercise were measured. Resting MSNA was lower in patients with T2DM than in healthy control subjects (P = 0.011). Resting MSNA was negatively correlated with haemoglobin A1c in all subjects (R = -0.45, P = 0.024). The parasympathetic components of heart rate variability and CBRS were negatively correlated with glycaemic/insulin indices in all subjects and even in the control group only (all, P < 0.05). In all subjects, the MSNA response to exercise was positively correlated with fasting blood glucose (R = 0.69, P < 0.001). Resting sympathetic activity and parasympathetic modulation of heart rate were decreased in relationship to abnormal glucose metabolism. Meanwhile, the sympathetic responses to handgrip were preserved in diabetics. The responses were correlated with glucose/insulin parameters throughout diabetic and control subjects. These results suggest the importance of a comprehensive assessment of autonomic function in T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Insulinas , Humanos , Força da Mão , Pressão Sanguínea/fisiologia , Sistema Nervoso Simpático/fisiologia , Barorreflexo/fisiologia , Frequência Cardíaca/fisiologia , Glucose , Músculo Esquelético/fisiologia
2.
EMBO Rep ; 23(10): e54322, 2022 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-35999696

RESUMO

The emergence of SARS-CoV-2 variants has exacerbated the COVID-19 global health crisis. Thus far, all variants carry mutations in the spike glycoprotein, which is a critical determinant of viral transmission being responsible for attachment, receptor engagement and membrane fusion, and an important target of immunity. Variants frequently bear truncations of flexible loops in the N-terminal domain (NTD) of spike; the functional importance of these modifications has remained poorly characterised. We demonstrate that NTD deletions are important for efficient entry by the Alpha and Omicron variants and that this correlates with spike stability. Phylogenetic analysis reveals extensive NTD loop length polymorphisms across the sarbecoviruses, setting an evolutionary precedent for loop remodelling. Guided by these analyses, we demonstrate that variations in NTD loop length, alone, are sufficient to modulate virus entry. We propose that variations in NTD loop length act to fine-tune spike; this may provide a mechanism for SARS-CoV-2 to navigate a complex selection landscape encompassing optimisation of essential functionality, immune-driven antigenic variation and ongoing adaptation to a new host.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/genética , Humanos , Filogenia , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
3.
J Pathol ; 259(2): 119-124, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36426824

RESUMO

The FOS gene family has been implicated in tumourigenesis across several tumour types, particularly mesenchymal tumours. The rare fibrous tumour desmoplastic fibroblastoma is characterised by overexpression of FOSL1. However, previous studies using cytogenetic and molecular techniques did not identify an underlying somatic change involving the FOSL1 gene to explain this finding. Prompted by an unusual index case, we report the discovery of a novel FOSL1 rearrangement in desmoplastic fibroblastoma using whole-genome and targeted RNA sequencing. We investigated 15 desmoplastic fibroblastomas and 15 fibromas of tendon sheath using immunohistochemistry, in situ hybridisation and targeted RNA sequencing. Rearrangements in FOSL1 and FOS were identified in 10/15 and 2/15 desmoplastic fibroblastomas respectively, which mirrors the pattern of FOS rearrangements observed in benign bone and vascular tumours. Fibroma of tendon sheath, which shares histological features with desmoplastic fibroblastoma, harboured USP6 rearrangements in 9/15 cases and did not demonstrate rearrangements in any of the four FOS genes. The overall concordance between FOSL1 immunohistochemistry and RNA sequencing results was 90%. These findings illustrate that FOSL1 and FOS rearrangements are a recurrent event in desmoplastic fibroblastoma, establishing this finding as a useful diagnostic adjunct and expanding the spectrum of tumours driven by FOS gene family alterations. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Fibroma Desmoplásico , Fibroma , Neoplasias de Tecidos Moles , Humanos , Fibroma Desmoplásico/diagnóstico , Fibroma Desmoplásico/genética , Fibroma Desmoplásico/patologia , Fibroma/genética , Rearranjo Gênico , Hibridização In Situ , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Ubiquitina Tiolesterase/genética
4.
Pediatr Dev Pathol ; 27(3): 260-265, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38098239

RESUMO

Wilms tumor (WT) is the commonest cause of renal cancer in children. In Europe, a diagnosis is made for most cases on typical clinical and radiological findings, prior to pre-operative chemotherapy. Here, we describe a case of a young boy presenting with a large abdominal tumor, associated with raised serum alpha-fetoprotein (AFP) levels at diagnosis. Given the atypical features present, a biopsy was taken, and histology was consistent with WT, showing triphasic WT, with epithelial, stromal, and blastemal elements present, and positive WT1 and CD56 immunohistochemical staining. During pre-operative chemotherapy, serial serum AFP measurements showed further increases, despite a radiological response, before a subsequent fall to normal following nephrectomy. The resection specimen was comprised of ~55% and ~45% stromal and epithelial elements, respectively, with no anaplasia, but immunohistochemistry using AFP staining revealed positive mucinous intestinal epithelium, consistent with the serum AFP observations. The lack of correlation between tumor response and serum AFP levels in this case highlights a more general clinical unmet need to identify WT-specific circulating tumor markers.


Assuntos
Biomarcadores Tumorais , Neoplasias Renais , Tumor de Wilms , alfa-Fetoproteínas , Humanos , Tumor de Wilms/diagnóstico , Tumor de Wilms/patologia , Tumor de Wilms/sangue , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/metabolismo , Masculino , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/análise , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Neoplasias Renais/sangue , Nefrectomia
5.
Eur Eat Disord Rev ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995266

RESUMO

OBJECTIVE: Evidence suggests that interpersonal stress plays a role in maintaining binge eating and purging (e.g., self-induced vomiting, misuse of laxatives). Stress is especially likely to promote engagement in maladaptive behaviour if the behaviour is habitual; therefore, individuals whose binge eating and/or purging are habitual may be particularly likely to engage in these behaviours in the context of interpersonal stress. We aimed to investigate this hypothesis in a sample of women with binge eating and/or purging using ecological momentary assessment (EMA). METHOD: Women (N = 81) with binge-eating and/or purging symptoms completed a self-report measure assessing habit strength of binge eating and purging followed by a 14-day EMA protocol assessing daily perceived interpersonal stress and binge-eating and purging episodes. RESULTS: Habit strength of purging moderated the within-person effect of interpersonal stress on purging frequency, such that higher daily stress was associated with greater same-day purging frequency when purging was more habitual. Contrary to expectations, the interactive effect of habit strength of binge eating and daily interpersonal stress on same-day binge-eating frequency was non-significant. CONCLUSIONS: Findings suggest that individuals with habitual purging may be vulnerable to engaging in purging when they are experiencing high levels of interpersonal stress.

6.
Eat Disord ; : 1-15, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38686640

RESUMO

Community evidence indicates high eating disorder (ED) and comorbid symptom severity among LGBTQ+ compared to cisgender heterosexual (CH) individuals. Little is known about such disparities in ED treatment samples, especially in outpatient treatment. We aimed to descriptively characterize and investigate baseline group differences in symptom severity between LGBTQ+ and CH ED outpatients at treatment intake. Data from 60 (22.3%) LGBTQ+ and 209 (77.7%) CH ED outpatients were used to examine: (1) demographic and diagnostic differences; (2) differences in ED, depressive, and emotion dysregulation symptoms. Objectives were tested using Fisher-Freeman-Halton exact and independent samples t-tests, and analyses of covariance adjusted for age and diagnosis, respectively. Most LGBTQ+ outpatients were bisexual (55.2%), and 6.5% identified as transgender and non-binary. LGBTQ+ outpatients presented to treatment at younger ages (Mean Difference [MD] = -3.39, p = .016) and reported more severe depressive symptoms (MD = 5.73, p = .004) than CH patients, but endorsed similar ED symptom and emotion dysregulation severity. Groups did not differ in other demographic or diagnostic characteristics. LGBTQ+ individuals may develop more severe depression and similarly severe EDs at earlier ages but seek outpatient care sooner than CH peers. Managing depressive symptoms may be particularly important for LGBTQ+ ED patients.

7.
Br J Cancer ; 129(9): 1451-1461, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37789102

RESUMO

BACKGROUND: MiR-371~373 and miR-302/367 cluster over-expression occurs in all malignant germ cell tumours (GCTs), regardless of age (paediatric/adult), site (gonadal/extragonadal), or subtype [seminoma, yolk sac tumour (YST), embryonal carcinoma (EC)]. Six of eight microRNAs from these clusters contain the seed sequence 'AAGUGC', determining mRNA targeting. Here we sought to identify the significance of these observations by targeting these microRNAs functionally. METHODS: We targeted miR-371~373 and/or miR-302/367 clusters in malignant GCT cell lines, using CRISPR-Cas9, gapmer primary miR-302/367 transcript inhibition, and peptide nucleic acid (PNA) or locked nucleic acid (LNA)-DNA inhibition targeting miR-302a-d-3p, and undertook relevant functional assays. RESULTS: MiR-302/367 cluster microRNAs made the largest contribution to AAGUGC seed abundance in malignant GCT cells, regardless of subtype (seminoma/YST/EC). Following the unsuccessful use of CRISPR-Cas9, gapmer, and PNA systems, LNA-DNA-based targeting resulted in growth inhibition in seminoma and YST cells. This was associated with the de-repression of multiple mRNAs targeted by AAGUGC seed-containing microRNAs, with pathway analysis confirming predominant disruption of Rho-GTPase signalling, vesicle organisation/transport, and cell cycle regulation, findings corroborated in clinical samples. Further LNA-DNA inhibitor studies confirmed direct cell cycle effects, with an increase of cells in G0/G1-phase and a decrease in S-phase. CONCLUSION: Targeting of specific miR-371~373 and miR-302/367 microRNAs in malignant GCTs demonstrated their functional significance, with growth inhibition mediated through cell cycle disruption.


Assuntos
MicroRNAs , Neoplasias Embrionárias de Células Germinativas , Seminoma , Neoplasias Testiculares , Masculino , Adulto , Humanos , Criança , MicroRNAs/genética , Seminoma/genética , Neoplasias Testiculares/patologia , Ciclo Celular , DNA
8.
Br J Haematol ; 202(5): 985-994, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37357529

RESUMO

Anaplastic large-cell lymphoma (ALCL) is a T-cell malignancy predominantly driven by the oncogenic anaplastic lymphoma kinase (ALK), accounting for approximately 15% of all paediatric non-Hodgkin lymphoma. Patients with central nervous system (CNS) relapse are particularly difficult to treat with a 3-year overall survival of 49% and a median survival of 23.5 months. The second-generation ALK inhibitor brigatinib shows superior penetration of the blood-brain barrier unlike the first-generation drug crizotinib and has shown promising results in ALK+ non-small-cell lung cancer. However, the benefits of brigatinib in treating aggressive paediatric ALK+ ALCL are largely unknown. We established a patient-derived xenograft (PDX) resource from ALK+ ALCL patients at or before CNS relapse serving as models to facilitate the development of future therapies. We show in vivo that brigatinib is effective in inducing the remission of PDX models of crizotinib-resistant (ALK C1156Y, TP53 loss) ALCL and furthermore that it is superior to crizotinib as a second-line approach to the treatment of a standard chemotherapy relapsed/refractory ALCL PDX pointing to brigatinib as a future therapeutic option.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Linfoma Anaplásico de Células Grandes , Criança , Humanos , Quinase do Linfoma Anaplásico , Crizotinibe/farmacologia , Crizotinibe/uso terapêutico , Receptores Proteína Tirosina Quinases/uso terapêutico , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Linfoma Anaplásico de Células Grandes/patologia , Xenoenxertos , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos Organofosforados/farmacologia , Compostos Organofosforados/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico
9.
Opt Express ; 31(1): 287-300, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36606967

RESUMO

We present a distributed fiber sensor capable of discriminating between temperature and strain while performing low-noise, dynamic measurements. This was achieved by leveraging recent advances in Brillouin and Rayleigh based fiber sensors. In particular, we designed a hybrid sensor that combines a slope-assisted Brillouin optical time domain analysis system with a Rayleigh-scattering-based frequency scanning optical time domain reflectometry system. These sub-systems combine state-of-the-art sensitivity with the ability to perform both dynamic and quasi-static measurements. This enabled a hybrid system capable of temperature/strain discrimination with a quasi-static temperature resolution of 16 m°C and a strain resolution of 140 nɛ along 500 m of single mode fiber with 5 m spatial resolution. In contrast to previously reported techniques, this approach also enabled dynamic measurements with a bandwidth of 1.7 kHz and temperature (strain) noise spectral density of 0.54 m°C/√Hz (4.5 nɛ/√Hz) while temperature/strain cross-sensitivity was suppressed by at least 25 dB. This represents a dramatic improvement in measurement speed and sensitivity compared with existing techniques capable of temperature/strain discrimination in standard single mode fiber.

10.
Opt Express ; 31(13): 20651-20664, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37381184

RESUMO

Persistent wideband radio frequency (RF) surveillance and spectral analysis is increasingly important, driven by the proliferation of wireless communication and RADAR technology. However, conventional electronic approaches are limited by the ∼1 GHz bandwidth of real-time analog-to-digital converters (ADCs). While faster ADCs exist, high data rates prohibit continuous operation, limiting these approaches to acquiring short snapshots of the RF spectrum. In this work, we introduce an optical RF spectrum analyzer designed for continuous, wideband operation. Our approach encodes the RF spectrum as sidebands on an optical carrier and relies on a speckle spectrometer to measure these sidebands. To achieve the resolution and update rate required for RF analysis, we use Rayleigh backscattering in single-mode fiber to rapidly generate wavelength-dependent speckle patterns with MHz-level spectral correlation. We also introduce a dual-resolution scheme to mitigate the trade-off between resolution, bandwidth, and measurement rate. This optimized spectrometer design enables continuous, wideband (15 GHz) RF spectral analysis with MHz-level resolution and a fast update rate of 385 kHz. The entire system is constructed using fiber-coupled off-the-shelf-components, providing a powerful new approach for wideband RF detection and monitoring.

11.
Pediatr Blood Cancer ; 70(8): e30426, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37243320

RESUMO

BACKGROUND/OBJECTIVES: Surgery is the mainstay of therapy for children with ovarian immature teratoma (IT), whereas adults receive adjuvant chemotherapy, except those with stage-I, grade-1 disease. In Brazil, children with metastatic ovarian IT received postoperative chemotherapy. This practice variation allowed evaluation of the value of chemotherapy, by comparison of Brazilian patients with those in the United States and United Kingdom. DESIGN/METHODS: From the Malignant Germ Cell International Consortium data commons, data on ovarian IT patients from two recently added Brazilian trials (TCG-99/TCG-2008) were compared with data from US/UK (INT-0106/GC-2) trials. Primary outcome measure was event-free (EFS) and overall survival (OS). RESULTS: Forty-two Brazilian patients were included (stage I: 27, stage II: 4, stage III: 8, stage IV: 3). Twenty-nine patients had surgery alone, whereas 13 patients received postoperative chemotherapy. The EFS and OS for entire cohort was 0.80 (95% CI: 0.64-0.89) and 0.97 (0.84-0.99). There was no difference in relapse risk based on stage, grade, or receipt of chemotherapy. Comparing the Brazilian cohort with 98 patients in US/UK cohort (stage I: 59, stage II: 12, stage III: 27), there was no difference in EFS and OS across all stages, despite 87% of stage II-IV Brazilian patients receiving postoperative chemotherapy compared with only 13% of US/UK patients. The EFS and OS for Brazilian compared with US/UK cohort was stage I: 88% versus 98% (p = .05), stage II-IV EFS: 67% versus 79% (p = .32), stage II-IV OS: 93% versus 97% (p = .44); amongst grade-3 patients, there was no difference in EFS or OS. CONCLUSION: Addition of postoperative chemotherapy did not improve outcome in children with ovarian IT, even at higher grade or stage, compared with surgery alone.


Assuntos
Neoplasias Ovarianas , Teratoma , Adulto , Feminino , Humanos , Criança , Estados Unidos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Teratoma/tratamento farmacológico , Teratoma/patologia , Quimioterapia Adjuvante
12.
J Infect Dis ; 226(2): 357-365, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35184187

RESUMO

BACKGROUND: Cytomegalovirus (CMV) is an important opportunistic pathogen after transplantation. Some virological variation in transplant recipients is explained by donor and recipient CMV serostatus, but not all. Circadian variability of herpesviruses has been described, so we investigated the effect of time of day of transplantation on posttransplant CMV viremia. METHODS: We performed a retrospective analysis of 1517 patients receiving liver or kidney allografts at a single center from 2002 to 2018. All patients were given preemptive therapy with CMV viremia monitoring after transplantation. Circulatory arrest and reperfusion time of donor organ were categorized into 4 periods. Patients were divided into serostatus groups based on previous CMV infection in donor and recipient. CMV viremia parameters were compared between time categories for each group. Factor analysis of mixed data was used to interrogate this complex data set. RESULTS: Live-donor transplant recipients were less likely to develop viremia than recipients of deceased-donor organs (48% vs 61%; P < .001). After controlling for this, there was no evidence of time of day of transplantation affecting CMV parameters in any serostatus group, by logistic regression or factor analysis of mixed data. DISCUSSION: We found no evidence for a circadian effect of transplantation on CMV viremia, but these novel results warrant confirmation by other centers.


Assuntos
Infecções por Citomegalovirus , Transplante de Órgãos , Antivirais/uso terapêutico , Ritmo Circadiano , Citomegalovirus , Humanos , Transplante de Órgãos/efeitos adversos , Estudos Retrospectivos , Carga Viral , Viremia/etiologia
13.
Lancet Oncol ; 23(5): e218-e228, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35489353

RESUMO

Homogeneous and common objective disease assessments and standardised response criteria are important for better international clinical trials for CNS germ cell tumours. Currently, European protocols differ from those of North America (the USA and Canada) in terms of criteria to assess radiological disease response. An international working group of the European Society for Paediatric Oncology Brain Tumour Group and North American Children's Oncology Group was therefore established to review existing literature and current practices, identify major challenges regarding imaging assessment, and develop consensus recommendations for imaging response assessment for patients with CNS germ cell tumours. New clinical imaging standards were defined for the most common sites of CNS germ cell tumour and for the definition of locoregional extension. These new standards will allow the evaluation of response to therapy in patients with CNS germ cell tumours to be more consistent, and facilitate direct comparison of treatment outcomes across international studies.


Assuntos
Neoplasias Encefálicas , Neoplasias Embrionárias de Células Germinativas , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Criança , Consenso , Diagnóstico por Imagem , Humanos , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/terapia , Resultado do Tratamento
14.
Br J Cancer ; 127(1): 137-144, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35449451

RESUMO

BACKGROUND: Whole-genome sequencing (WGS) of cancers is becoming an accepted component of oncological care, and NHS England is currently rolling out WGS for all children with cancer. This approach was piloted during the 100,000 genomes (100 K) project. Here we share the experience of the East of England Genomic Medicine Centre (East-GMC), reporting the feasibility and clinical utility of centralised WGS for individual children locally. METHODS: Non-consecutive children with solid tumours were recruited into the pilot 100 K project at our Genomic Medicine Centre. Variant catalogues were returned for local scrutiny and appraisal at dedicated genomic tumour advisory boards with an emphasis on a detailed exploration of potential clinical value. RESULTS: Thirty-six children, representing one-sixth of the national 100 K cohort, were recruited through our Genomic Medicine Centre. The diagnoses encompassed 23 different solid tumour types and WGS provided clinical utility, beyond standard-of-care assays, by refining (2/36) or changing (4/36) diagnoses, providing prognostic information (8/36), defining pathogenic germline mutations (1/36) or revealing novel therapeutic opportunities (8/36). CONCLUSION: Our findings demonstrate the feasibility and clinical value of centralised WGS for children with cancer. WGS offered additional clinical value, especially in diagnostic terms. However, our experience highlights the need for local expertise in scrutinising and clinically interpreting centrally derived variant calls for individual children.


Assuntos
Neoplasias , Medicina Estatal , Criança , Estudos de Viabilidade , Mutação em Linhagem Germinativa , Humanos , Neoplasias/genética , Sequenciamento Completo do Genoma
15.
Br J Cancer ; 127(9): 1577-1583, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36229581

RESUMO

Germ cell tumours (GCTs) are a heterogeneous group of rare neoplasms that present in different anatomical sites and across a wide spectrum of patient ages from birth through to adulthood. Once these strata are applied, cohort numbers become modest, hindering inferences regarding management and therapeutic advances. Moreover, patients with GCTs are treated by different medical professionals including paediatric oncologists, neuro-oncologists, medical oncologists, neurosurgeons, gynaecological oncologists, surgeons, and urologists. Silos of care have thus formed, further hampering knowledge dissemination between specialists. Dedicated biobank specimen collection is therefore critical to foster continuous growth in our understanding of similarities and differences by age, gender, and site, particularly for rare cancers such as GCTs. Here, the Malignant Germ Cell International Consortium provides a framework to create a sustainable, global research infrastructure that facilitates acquisition of tissue and liquid biopsies together with matched clinical data sets that reflect the diversity of GCTs. Such an effort would create an invaluable repository of clinical and biological data which can underpin international collaborations that span professional boundaries, translate into clinical practice, and ultimately impact patient outcomes.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Criança , Humanos , Adulto , Masculino , Pesquisa Translacional Biomédica , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/patologia
16.
Pediatr Blood Cancer ; 69(1): e29359, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34520101

RESUMO

BACKGROUND: Patients with localized intracranial germinoma have excellent survival. Reducing treatment burden and long-term sequelae is a priority. Intensive inpatient chemotherapy (e.g., carboPEI = carboplatin/etoposide/ifosfamide) has been effectively employed to reduce radiotherapy treatment volume/dose. Outpatient-based carboplatin monotherapy is associated with excellent outcomes in metastatic testicular seminoma (an identical pathology), and successful vinblastine monotherapy induction (with 77% tumor volume reduction after just two weekly vinblastine doses) has recently been reported in an intracranial germinoma patient. METHODS: Adapted UK guidelines for germ cell tumor management were distributed during the COVID-19 pandemic, including nonstandard treatment options to reduce hospital visits and/or admissions. This included vinblastine monotherapy for intracranial germinoma (6 mg/m2 intravenously, or 4 mg/m2 for moderate count suppression, delivered weekly). We describe two such patients treated using this approach. RESULTS: A 30-year-old male with a localized pineal tumor received 12-week vinblastine induction, with >60% volume reduction, prior to definitive radiotherapy. A 12-year-old female with a metastatic suprasellar tumor and progression at all sites of disease whilst awaiting proton radiotherapy received two vinblastine doses with good early response, including 36% primary tumor volume reduction. The patients tolerated vinblastine well. CONCLUSION: Patients with intracranial germinoma have excellent outcomes, and reduction of late effects remains a priority. The description of vinblastine monotherapy in these intracranial germinoma patients warrants further exploration.


Assuntos
Neoplasias Encefálicas , Germinoma , Neoplasias Embrionárias de Células Germinativas , Vimblastina , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , COVID-19 , Carboplatina/uso terapêutico , Criança , Etoposídeo/uso terapêutico , Feminino , Germinoma/tratamento farmacológico , Germinoma/radioterapia , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/radioterapia , Pandemias , Vimblastina/uso terapêutico
17.
J Pediatr Hematol Oncol ; 44(3): e736-e739, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34001797

RESUMO

BACKGROUND: Adrenal masses are rare in children and most commonly present with clinical features of virilization in the absence of activation of the pituitary axis-gonadotrophin-independent precocious puberty. OBSERVATIONS: We report an unusual case of a 7-year-old girl who presented with clinical signs suggestive of exposure to both androgens and estrogens. Imaging revealed a left-sided adrenal mass with no evidence of metastasis. She underwent successful laparoscopic unilateral adrenalectomy. Histology confirmed an adrenal adenoma. CONCLUSION: We conclude that adrenocortical tumors should be considered in children presenting with gonadotrophin-independent precocious puberty and raised estrogens.


Assuntos
Neoplasias das Glândulas Suprarrenais , Adenoma Adrenocortical , Puberdade Precoce , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/cirurgia , Adenoma Adrenocortical/diagnóstico , Adenoma Adrenocortical/cirurgia , Criança , Estrogênios , Feminino , Humanos , Puberdade Precoce/diagnóstico , Puberdade Precoce/etiologia
18.
Pediatr Dev Pathol ; 25(2): 168-173, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34428078

RESUMO

Hodgkin lymphoma (HL) can present with extra-nodal disease, but spinal cord compression is exceptionally rare. We describe a 15-year-old presenting with hip/back pain with normal initial examination. Persistent pain and raised inflammatory markers prompted further investigation with MRI, which revealed an epidural mass causing spinal cord compression. On examination, there was no palpable lymphadenopathy or cauda equina syndrome, but absent lower limb reflexes were noted. Following multidisciplinary discussion, it was determined that cauda equina syndrome was imminent and therefore surgical debulking was undertaken, both to prevent this complication and establish a diagnosis. At surgery, the tumor was highly vascular. Frozen section confirmed lesional material. Following surgery, and given the frozen section findings, a short course of steroids was commenced to reduce any peri-surgical edema. Unfortunately, histopathology was ultimately non-diagnostic, due to failure of immunohistochemistry on technically challenging material. Consequently, ultrasound-guided excision biopsy of a (non-palpable) cervical lymph node was performed five days later; histopathology showed typical effacement of the normal architecture and a conspicuous population of CD15/CD30-positive larger pale cells present, confirming nodular sclerosis classic HL, despite recent steroids. We review the available literature for HL presenting with spinal cord compression and describe the challenges for diagnosis and initial management in such cases.


Assuntos
Síndrome da Cauda Equina , Doença de Hodgkin , Compressão da Medula Espinal , Adolescente , Síndrome da Cauda Equina/complicações , Doença de Hodgkin/complicações , Doença de Hodgkin/diagnóstico , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Compressão da Medula Espinal/complicações , Compressão da Medula Espinal/etiologia
19.
Int J Eat Disord ; 55(2): 193-206, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35037275

RESUMO

OBJECTIVE: No study to date has investigated an intervention program for male athletes that targets eating disorder risk factors. The purpose of this study was to measure the effects of the Male Athlete Body Project (MABP), an adaptation of the Female Athlete Body Project on body dissatisfaction, drive for muscularity, body-ideal internalization, and muscle dysmorphia. METHOD: Participants were 79 male collegiate athletes who were randomized to the MABP (n = 39) or an assessment-only control condition (n = 40). All participants completed psychometrically validated measures at three time points: baseline, post-treatment (3 weeks after baseline for the control condition), and 1-month follow-up. RESULTS: Hierarchical Linear Modeling assessed differences between conditions across time. Interaction effects revealed that participation in the MABP improved satisfaction with specific body parts and reduced drive for muscularity and body-ideal internalization at post-treatment compared to a control group. Athletes in the MABP also reported increased body areas satisfaction and reductions in drive for muscularity at 1-month follow-up. Reductions in supplement use were observed at 1-month follow-up only. DISCUSSION: This study provides preliminary evidence of the efficacy of the MABP in reducing some eating disorder risk factors up to 1 month after the intervention; follow-up study considerations are discussed. CLINICAL TRIAL REGISTRATION NUMBER: NCT04077177 PUBLIC SIGNIFICANCE: This study highlights the importance of eating disorder and body image intervention efforts for male athletes. Findings suggest that male college athletes who attended a 3-session group intervention based on a well-established program for college women experienced an increase in satisfaction with specific body areas and a reduction in some eating disorder risk factors (e.g., drive for muscularity, supplement use, and body-ideal internalization) compared to a control group.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Corpo Humano , Atletas , Imagem Corporal , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/prevenção & controle , Feminino , Seguimentos , Humanos , Masculino
20.
J Emerg Med ; 62(3): e65-e68, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35065866

RESUMO

BACKGROUND: Head injuries are an important cause of morbidity and mortality in children and young adults. There are multiple sight-threatening complications of head injury, even in closed head injury without visible violation of the globe or orbits. One such entity is traumatic optic neuropathy. CASE REPORT: Herein we describe a case of traumatic optic neuropathy in an otherwise healthy teenage patient who suffered total monocular vision loss after a fall and without any other injuries on examination. Unfortunately, the prognosis for this condition is relatively poor in terms of visual recovery. Though much research has been conducted attempting to treat this condition, to date there have been no studies showing a clear benefit of medical or surgical intervention. Why Should an Emergency Physician Be Aware of This? Although there is no proven treatment for traumatic optic neuropathy, emergency physicians may encounter this in their practice while caring for both pediatric and adult patients presenting with head injury. Having more background knowledge on this condition will enhance emergency physicians' ability to consult with subspecialist providers as well as to educate patients and their families on their condition and prognosis.


Assuntos
Traumatismos Cranianos Fechados , Traumatismos do Nervo Óptico , Adolescente , Cegueira/etiologia , Criança , Traumatismos Cranianos Fechados/complicações , Traumatismos Cranianos Fechados/diagnóstico , Humanos , Traumatismos do Nervo Óptico/diagnóstico , Traumatismos do Nervo Óptico/etiologia , Traumatismos do Nervo Óptico/terapia , Órbita , Visão Monocular , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA