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1.
Emerg Infect Dis ; 27(10): 2677-2680, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34545785

RESUMO

We describe a case of hemorrhagic fever with renal syndrome caused by Seoul virus in a woman in Scotland, UK. Whole-genome sequencing showed the virus belonged to a lineage characterized by recent international expansion, probably driven by trade in pet rats.


Assuntos
Febre Hemorrágica com Síndrome Renal , Vírus Seoul , Animais , Febre Hemorrágica com Síndrome Renal/diagnóstico , Humanos , Rim , Ratos , Escócia/epidemiologia , Vírus Seoul/genética , Reino Unido
2.
Respiration ; : 1-9, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384085

RESUMO

BACKGROUND: Lung-sparing cytoreductive surgery by extended pleurectomy and decortication (EPD) in combination with hyperthermic intrathoracic chemoperfusion (HITOC) forms a promising treatment strategy for malignant pleural mesothelioma and recurrent pleural thymic malignancies. OBJECTIVES: The objective of this study was to scrutinize the surgical procedure and perioperative patient management with emphasis on perioperative morbidity and local tumor control. METHODS: In 2014, a standardized EPD and HITOC procedure was implemented at the Thoraxklinik Heidelberg. This retrospective analysis included clinical data of consecutive patients with pleural mesothelioma and pleural metastasized malignancies treated by EPD and HITOC. The surgical procedure, perioperative management, lung function data, and progression-free survival (PFS) were analyzed. RESULTS: In the time range between April 2, 2014 and July 2018, 76 patients with pleural malignancies have been treated with EPD and HITOC, and were analyzed retrospectively. It included 61 patients with pleural mesothelioma and 15 patients with pleural metastases of thymic malignancies (12), non-small cell lung cancer (1), colorectal carcinoma (1), and sarcoma (1). Perioperative morbidity following EPD and HITOC treatments represented 23.7% of overall malignancies, while 30- and 90-day mortality were 0 and 1.3%, respectively. Median PFS lasted 18.4 months for mesothelioma and 72.2 months for thymic malignancies. CONCLUSION: Combining EPD with HITOC can be performed in patients with either pleural mesothelioma or pleural metastases resulting in low perioperative morbidity and mortality as well as remarkable local tumor control.

4.
Front Oncol ; 11: 673901, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307143

RESUMO

Background: Large-cell neuroendocrine lung carcinoma (LCNEC) is a rare pulmonary neoplasm with poor prognosis and limited therapeutic options. Methods: We retrospectively analyzed all patients with metastatic LCNEC in the records of a large German academic center since 2010. Results: 191 patients were identified with a predominance of male (68%) smokers (92%) and a median age of 65 years. The single most important factor associated with outcome was the type of systemic treatment, with a median overall survival (OS) of 26.4 months in case of immune checkpoint inhibitor administration (n=13), 9.0 months for other patients receiving first-line platinum doublets (n=129), and 4.0 months with non-platinum chemotherapies (n=17, p<0.01). Other patient characteristics independently associated with longer OS were a lower baseline serum LDH (hazard ratio [HR] 0.54, p=0.008) and fewer initial metastatic sites (HR 0.52, p=0.006), while the platinum drug type (cisplatin vs. carboplatin) and cytotoxic partner (etoposide vs. paclitaxel), patients' smoking status and baseline levels of tumor markers (NSE, CYFRA 21-1, CEA) did not matter. 12% (23/191) of patients forewent systemic treatment, mainly due to tumor-related clinical deterioration (n=13), while patient refusal of therapy (n=5) and severe concomitant illness (n=5) were less frequent. The attrition between successive treatment lines was approximately 50% and similar for platinum-based vs. other therapies, but higher in case of a worse initial ECOG status or higher serum LDH (p<0.05). 19% (36/191) of patients had secondary stage IV disease and showed fewer metastatic sites, better ECOG status and longer OS (median 12.6 vs. 8.7 months, p=0.030). Among the 111 deceased patients with palliative systemic treatment and complete follow-up, after exclusion of oligometastatic cases (n=8), administration of local therapies (n=63 or 57%) was associated with a longer OS (HR 0.58, p=0.008), but this association did not persist with multivariable testing. Conclusions: Highly active systemic therapies, especially immunotherapy and platinum doublets, are essential for improved outcome in LCNEC and influence OS stronger than clinical disease parameters, laboratory results and other patient characteristics. The attrition between chemotherapy lines is approximately 50%, similar to other NSCLC. Patients with secondary metastatic disease have a more favorable clinical phenotype and longer survival.

5.
J Obstet Gynaecol Can ; 43(7): 864-868, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34253305

RESUMO

A 39-year-old woman presented with bleeding 4 months after a surgical termination of pregnancy. Persistent beta-human chorionic gonadotropin levels were suggestive of retained products of conception (RPOC). However, multimodal imaging revealed a concurrent uterine arteriovenous malformation (AVM). Although most stable AVMs can be managed conservatively, the need for surgical management of chronic RPOC and consequential hemorrhage risk complicates this approach. Patient-determined management prioritized blood conservation while minimizing risks to fertility. This case is discussed with respect to the rare concurrent existence of RPOC and AVM. Little is known regarding the optimal tandem therapeutic approach. As depicted, successful treatment requires careful diagnostic workup and a multidisciplinary approach.


Assuntos
Malformações Arteriovenosas , Anormalidades Urogenitais , Adulto , Malformações Arteriovenosas/complicações , Malformações Arteriovenosas/diagnóstico por imagem , Feminino , Humanos , Gravidez , Hemorragia Uterina/etiologia
6.
Front Oncol ; 11: 703893, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268127

RESUMO

Introduction: PD-(L)1 inhibitors have improved prognosis of non-small-cell lung cancer (NSCLC), but can also cause immune-related adverse events (irAEs) that complicate management. Methods: We analyzed NSCLC patients receiving PD-(L)1 inhibitors from 2012 to 2020 in a German academic center. Results: IrAE showed comparable frequencies in stage IV (198/894 or 22%) vs. III (14/45 or 31%, p = 0.15), after anti-PD-(L)1 monotherapy vs. chemoimmunotherapy (139/483 vs. 58/213, p = 0.75), and across treatment lines. In stage IV, irAE occurred after 3.1 months in median, affected multiple organs (median 2) in 27/894 patients and were associated with PD-L1 positivity (25 vs. 14%, p = 0.003), lower neutrophil-to-lymphocyte ratios (29 vs. 17%, p < 0.001 for NLR dichotomized at 5), better ECOG status (26 vs. 18% for 0 vs. 1, p = 0.004), but not related to age, sex, smoking and palliative radiotherapy. Two hundred thirty two irAEs occurred mostly in endocrine glands (4.9%), lungs (4.4%), the musculoskeletal system (4.2%), colon (4.1%), liver (3.7%), and skin (2.6%), while pneumonitis was most frequent with durvalumab following definitive chemoradiation (16% or 7/45, p < 0.01). IrAE severity was grade 1 in 11%, 2 in 41%, 3 in 36%, and 4 in 11% events, while two were lethal (<1%, myocarditis and pneumonitis). Therapy was suspended in 72%, while steroids were initiated in 66% and complemented by other immunosuppressants in 6%, with longest treatment duration for rheumatic events (mean >3 months), and average cumulative prednisone doses >700 mg for all organs, except for skin. Patients developing irAE had longer progression-free (PFS) and overall survival (OS) in multivariable 12/14-week landmark analyses including ECOG status, treatment line, treatment type, PD-L1 TPS, and NLR (median PFS 17 vs. 10 months, HR = 0.68, p = 0.009; median OS 37 vs. 15 months, HR = 0.40, p < 0.001), regardless of grade. OS was longest with skin (95% at 2 years) and shortest with pneumonitis, hepatitis, neurologic, and cardiologic irAE (38, 37, 28, and 0% at 2 years, p < 0.001). Conclusions: Approximately one-fourth of immunotherapy-treated NSCLC patients develop irAEs, most of which necessitate treatment suspension and steroids. Despite more frequent occurrence with PD-L1 positive tumors, lower NLR, and better ECOG PS, irAEs are independently associated with longer survival, especially when affecting the skin. Lethality is below 1%.

7.
J Hepatol ; 75(2): 462-473, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33974951

RESUMO

The hepatitis C virus (HCV) is an extremely diverse virus, subtypes of which are distributed variably around the world. Viral genotypes may be divided into epidemic subtypes; those that have become prevalent globally, and endemic subtypes that have a more limited distribution, mainly in Africa and Asia. The high variability of endemic strains reflects evolutionary origins in the locations where they are found. This increased genetic diversity raises the possibility of resistance to pan-genotypic direct-acting antiviral regimens. While many endemic subtypes respond well to direct-acting antiviral therapies, others, for example genotypes 1l, 3b and 4r, do not respond as well as predicted. Many genotypes that are rare in high-income countries but common in other parts of the world have not yet been fully assessed in clinical trials. Further sequencing and clinical studies in sub-Saharan Africa and Asia are indicated to monitor response to treatment and to facilitate the World Health Organization's 2030 elimination strategy.

8.
Foot (Edinb) ; 47: 101785, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33957528

RESUMO

Dislocations of the first metatarsophalangealjoint are rare, and recurrent dislocations unique. A national-level Kabaddi player dislocated his right first metatarsophalangeal joint while playing a game bear footed. After self-manipulative reduction, the patient had multiple dislocations. The patient reported after a year of injury with complaints of recurrent medial dislocations of the first metatarsophalangeal joint. At surgery, reconstruction of deficient lateral capsule-ligamentous structures of the first metatarsophalangeal joint was done with Palmaris longus autograft. The patient returned to sports in six months and was followed up for more than two years. The case is unique in the form that recurrent medial dislocation of first metatarsophalangeal dislocation is not described. LEVEL OF CLINICAL EVIDENCE: Level V.


Assuntos
Hallux , Luxações Articulares , Articulação Metatarsofalângica , Procedimentos Cirúrgicos Reconstrutivos , Atletas , Humanos , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/cirurgia , Articulação Metatarsofalângica/diagnóstico por imagem , Articulação Metatarsofalângica/cirurgia
9.
J Infect ; 83(1): 96-103, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33895226

RESUMO

OBJECTIVES: Patients requiring haemodialysis are at increased risk of serious illness with SARS-CoV-2 infection. To improve the understanding of transmission risks in six Scottish renal dialysis units, we utilised the rapid whole-genome sequencing data generated by the COG-UK consortium. METHODS: We combined geographical, temporal and genomic sequence data from the community and hospital to estimate the probability of infection originating from within the dialysis unit, the hospital or the community using Bayesian statistical modelling and compared these results to the details of epidemiological investigations. RESULTS: Of 671 patients, 60 (8.9%) became infected with SARS-CoV-2, of whom 16 (27%) died. Within-unit and community transmission were both evident and an instance of transmission from the wider hospital setting was also demonstrated. CONCLUSIONS: Near-real-time SARS-CoV-2 sequencing data can facilitate tailored infection prevention and control measures, which can be targeted at reducing risk in these settings.


Assuntos
COVID-19 , SARS-CoV-2 , Teorema de Bayes , Hospitais , Humanos , Epidemiologia Molecular , Diálise Renal/efeitos adversos
11.
J Obstet Gynaecol Can ; 43(11): 1260-1266, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33895334

RESUMO

OBJECTIVE: Nutritional and financial needs increase during pregnancy, making pregnant women particularly vulnerable to food insecurity. Our objective was to document the prevalence of food insecurity among pregnant women receiving prenatal care in an urban centre in Canada and to identify factors associated with food insecurity. METHODS: This cross-sectional study recruited pregnant women receiving prenatal care at one of two Toronto hospitals: Site 1 and Site 2 (serving a more disadvantaged population) between October 1, 2018 and October 1, 2019. Demographic information was collected, and the U.S. Household Food Security Survey Module was used to assess food security. Comparisons were made using χ2 tests, two-tailed t tests, or Mann-Whitney tests for categorical and continuous variables, as appropriate. Binary logistic regression and multivariate analyses were performed to assess associations with food insecurity and differences between hospitals sites. RESULTS: We recruited 626 participants (316 at Site 1 and 310 at Site 2). Prevalence of food insecurity was 12.8% among all participants with Site 2 having nearly 5 times the prevalence of Site 1 (66/310 [21.3%] vs. 14/316 [4.4%]; P = 0.001). Several factors were associated with food insecurity, with non-White ethnicity (OR 2.04; 95% CI 0.98-4.25, P = 0.055] and lower household income (OR 37.53; 95% CI 14.04-100, P < 0.001 when less than CAD $23 000/y) being the most robust. CONCLUSION: This Canadian study documented the prevalence of and factors associated with food insecurity in pregnancy. Targeted interventions to help low-income women and programs geared towards non-White women may be beneficial in addressing food insecurity among pregnant women.


Assuntos
Insegurança Alimentar , Gestantes , Canadá/epidemiologia , Estudos Transversais , Feminino , Abastecimento de Alimentos , Humanos , Gravidez , Prevalência , Fatores Socioeconômicos
12.
Indian J Orthop ; 55(2): 333-341, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33927811

RESUMO

Introduction: Ankle arthroscopy has come a long way since it was thought, it is not feasible because of tight joint and anatomical characteristics of ankle joint. The same anatomical features like capsular attachment and safe accessory portals are used to access the whole joint even with a rigid arthroscope. Ankle distraction method was routinely used to access the anterior ankle. However, nowadays, anterior arthroscopy is done in dorsiflexion as this increases the anterior ankle joint volume, and thereby easy access to various anatomical structures. On the other hand, intermittent traction is used to access the posterior ankle. Initially used as a diagnostic tool, ankle arthroscopy is now used extensively as a therapeutic and reconstruction tool. New evidence is published for all inside ligament reconstructions, effective management of impingement syndromes, and osteochondral lesions. The indications are being extended to fracture management and arthrodesis. Methodology: This narrative review was performed following a literature search in the Pubmed database and Medline using the following keywords: ankle arthroscopy, portals, ankle OCD, functional outcome. Related articles were then reviewed. Conclusion: Complications rate is reduced with a better understanding of the relative anatomy of surrounding neurovascular structures and tendons with regard to the position of ankle joint. This review on ankle arthroscopy focuses on anatomy, indications, and complications. Ankle arthroscopy is a safe and elegant tool as any other joint arthroscopy.

13.
J Cardiovasc Magn Reson ; 23(1): 44, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794918

RESUMO

The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). The SCMR web site ( https://www.scmr.org ) hosts a case series designed to present case reports demonstrating the unique attributes of CMR in the diagnosis or management of cardiovascular disease. Each clinical presentation is followed by a brief discussion of the disease and unique role of CMR in disease diagnosis or management guidance. By nature, some of these are somewhat esoteric, but all are instructive. In this publication, we provide a digital archive of the 2019 Case of the Week series as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine.


Assuntos
Síndrome de Churg-Strauss/diagnóstico por imagem , Imageamento por Ressonância Magnética , Trombose/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Antineoplásicos/efeitos adversos , Cardiotoxicidade , Síndrome de Churg-Strauss/fisiopatologia , Síndrome de Churg-Strauss/terapia , Diagnóstico Diferencial , Feminino , Neoplasias Cardíacas/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Trombose/fisiopatologia , Trombose/terapia , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/terapia , Função Ventricular Esquerda/efeitos dos fármacos , Adulto Jovem
14.
BMC Nutr ; 7(1): 9, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33731225

RESUMO

BACKGROUND: Sickle cell disease (SCD) is an inherited blood disorder that predominantly affects individuals in sub-Saharan Africa. However, research that elucidates links between SCD pathophysiology and nutritional status in African patients is lacking. This systematic review aimed to assess the landscape of studies in sub-Saharan Africa that focused on nutritional aspects of SCD, and highlights gaps in knowledge that could inform priority-setting for future research. METHODS: The study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Inclusion criteria comprised original, peer-reviewed research published between January 1995 and November 2020 involving individuals in Africa with any phenotypic variant of SCD and at least one nutritional status outcome. Nutritional status outcomes were defined as those that assessed dietary intakes, growth/anthropometry, or nutritional biomarkers. Databases used were Ovid Embase, Medline, Biosis and Web of Science. RESULTS: The search returned 526 articles, of which 76 were included in the final analyses. Most investigations (67%) were conducted in Nigeria. Studies were categorized into one of three main categories: descriptive studies of anthropometric characteristics (49%), descriptive studies of macro- or micronutrient status (41%), and interventional studies (11%). Findings consistently included growth impairment, especially among children and adolescents from sub-Saharan Africa. Studies assessing macro- and micronutrients generally had small sample sizes and were exploratory in nature. Only four randomized trials were identified, which measured the impact of lime juice, long-chain fatty acids supplementation, ready-to-use supplementary food (RUSF), and oral arginine on health outcomes. CONCLUSIONS: The findings reveal a moderate number of descriptive studies, most with small sample sizes, that focused on various aspects of nutrition and SCD in African patients. There was a stark dearth of interventional studies that could be used to inform evidence-based changes in clinical practice. Findings from the investigations were generally consistent with data from other regional settings, describing a significant risk of growth faltering and malnutrition among individuals with SCD. There is an unmet need for clinical research to better understand the potential benefits of nutrition-related interventions for patients with SCD in sub-Saharan Africa to promote optimal growth and improve health outcomes.

15.
J Am Med Inform Assoc ; 28(7): 1497-1506, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-33779728

RESUMO

OBJECTIVE: The prevalence of social media for sharing personal thoughts makes it a viable platform for the assessment of suicide risk. However, deep learning models are not able to capture the diverse nature of linguistic choices and temporal patterns that can be exhibited by a suicidal user on social media and end up overfitting on specific cues that are not generally applicable. We propose Adversarial Suicide assessment Hierarchical Attention (ASHA), a hierarchical attention model that employs adversarial learning for improving the generalization ability of the model. MATERIAL AND METHODS: We assess the suicide risk of a social media user across 5 levels of increasing severity of risk. ASHA leverages a transformer-based architecture to learn the semantic nature of social media posts and a temporal attention-based long short-term memory architecture for the sequential modeling of a user's historical posts. We dynamically generate adversarial examples by adding perturbations to actual examples that can simulate the stochasticity in historical posts, thereby making the model robust. RESULTS: Through extensive experiments, we establish the face-value of ASHA and show that it significantly outperforms existing baselines, with the F1 score of 64%. This is a 2% and a 4% increase over the ContextBERT and ContextCNN baselines, respectively. Finally, we discuss the practical applicability and ethical aspects of our work pertaining to ASHA, as a human-in-the-loop framework. DISCUSSION AND CONCLUSIONS: Adversarial samples can be helpful in capturing the diverse nature of suicidal ideation. Through ASHA, we hope to form a component in a larger human-in-the-loop infrastructure for suicide risk assessment on social media.


Assuntos
Mídias Sociais , Coleta de Dados , Humanos , Medição de Risco , Semântica , Ideação Suicida
16.
Cell ; 184(5): 1171-1187.e20, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33621484

RESUMO

SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.


Assuntos
COVID-19/imunologia , Aptidão Genética , Evasão da Resposta Imune , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Enzima de Conversão de Angiotensina 2/química , Anticorpos Neutralizantes/genética , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/virologia , Humanos , Mutação , Filogenia , SARS-CoV-2/química , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/química , Virulência
19.
Clin Lung Cancer ; 22(2): 142-146, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33158765

RESUMO

BACKGROUND: In selected patients with early-stage malignant pleural mesothelioma (MPM), a multimodal therapy that includes surgical cytoreduction, chemotherapy, and/or radiotherapy is recommended. Several clinical trials have demonstrated the beneficial effects of immune checkpoint inhibitors in pretreated MPM patients with advanced disease. Recent clinical data have suggested that the combination of chemotherapy and checkpoint inhibition might improve efficacy. TRIAL DESIGN: The NICITA (nivolumab with chemotherapy in pleural mesothelioma after surgery) trial is a prospective, 1:1 randomized, open-label, multicenter phase II clinical trial (ClinicalTrials.gov identifier, NCT04177953). Ninety-two patients with MPM epithelioid subtype, who had undergone extended pleurectomy and decortication with or without hyperthermic intrathoracic chemoperfusion, will be included to receive adjuvant treatment. All patients will receive ≤ 4 cycles of platinum-based chemotherapy with pemetrexed (arms A and B). Patients in arm B will additionally receive nivolumab, together with the adjuvant chemotherapy, and subsequently for ≤ 12 cycles as maintenance therapy. The primary endpoint of this study is the time-to-next-treatment. The secondary endpoints include progression-free survival, overall survival, proportion of patients with treatment beyond progression, duration of treatment beyond progression in this population, and quality of life. CONCLUSION: This prospective trial will contribute data to assess the efficacy of standard chemotherapy combined with nivolumab in the context of multimodal management of early-stage MPM. The study is currently enrolling patients.

20.
J Obstet Gynaecol Can ; 43(3): 372-375, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32962967

RESUMO

The University of Toronto launched a longitudinal integrated clerkship (LIC) pilot project in 2014. Our aim was to evaluate LIC student outcomes in obstetrics and gynaecology compared with those of traditional block students. LIC and block students underwent identical evaluations, including written and oral exams, as well as clinical assessments from the ward. LIC student scores in each domain were compared with those of the traditional block students over 4 years. There were no differences in overall pass/fail status between LIC and block students. Thus, our LIC design could be appropriately modeled at other teaching institutions contemplating introducing an LIC stream.


Assuntos
Estágio Clínico/normas , Currículo/normas , Ginecologia/educação , Obstetrícia/educação , Educação de Graduação em Medicina , Avaliação Educacional , Ginecologia/normas , Humanos , Obstetrícia/normas , Projetos Piloto , Melhoria de Qualidade , Estudantes de Medicina
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