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BACKGROUND: The aim of this study was to characterize the prevalence of self-reported adverse health outcomes (AHOs), track changes in AHOs, and examine their impact on health-related quality of life (HrQoL) in testicular cancer survivors (TCSs) who were diagnosed between 1980 and 1994. These assessments were conducted during two survey waves (SWs), with the first occurring â¼12 years after surgery-only or platinum-based chemotherapy (PBCT), and the second â¼28 years after initial treatment. The study primarily focused on 'typical AHOs', which included Peripheral Sensory Neuropathy (PSN), Raynaud's phenomenon, Tinnitus, and Hearing loss. PATIENTS AND METHODS: A total of 427 TCSs were included in the evaluation, distributed as follows: surgery-only group (n = 155), PBCT-standard group with ≤850 mg cisplatin (n = 222), and PBCT-high group with >850 mg cisplatin (n = 50). For comparison of HrQoL, men from the general population served as a control group (referred to as 'Norms'). The statistical significance level was set at P < 0.05, and clinical importance, in terms of testing HrQoL differences, was defined as Δ ≥2.5 points. RESULTS: A higher number of TCSs who underwent PBCT reported experiencing typical AHOs compared with those who had surgery only. The highest prevalence rates were observed among TCSs who had undergone PBCT-high. Further, the number of TCSs describing typical AHOs, except Raynaud's phenomenon, increased during the observation period of 16 years. At the last SW, a median of 4 AHOs (any type) were reported after PBCT-high compared with a median of 2 AHOs after Surgery-only or after PBCT-standard. With Surgery-only as reference, PBCT-high, but not PBCT-standard, was associated with decreasing physical HrQoL in the last SW (A2 Regression coefficient: -4.3; P = 0.008). When comparing all TCSs with Norms no clinically important difference in physical and mental HrQoL was observed at either SW. However, at the last SW, TCSs after PBCT-high therapy represented a subgroup of TCSs with clinically important impairment of HRQoL. Of the typical AHOs, only PSN reduced HrQoL. Chronic fatigue, pain, anxiety/depression, sexual dysfunction, unemployment, being single, and low education were additional covariates. CONCLUSIONS: After a median of 28 years since their treatment, HrQoL in TCSs was found to be comparable to that of Norms. This similarity held true even though AHOs, especially after PBCT-high, were becoming more prevalent among TCSs. The study revealed that individuals with a history of PBCT-high are at a high risk of experiencing a significantly increased prevalence of long-term AHOs, which subsequently leads to diminished HrQoL. It is crucial to recognize and provide specialized attention to these TCSs during lifelong follow-up care.
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Neoplasias Testiculares , Masculino , Humanos , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/epidemiologia , Qualidade de Vida , Cisplatino , Fatores de Risco , Sobreviventes , Avaliação de Resultados em Cuidados de SaúdeRESUMO
The accuracy of contemporary risk scores in predicting perioperative mortality in infective endocarditis (IE) remains controversial. The aim is to evaluate the performance of existent mortality risk scores for cardiovascular surgery in IE and the impact on operability at high-risk thresholds. A single-center retrospective review of adult patients diagnosed with acute left-sided IE undergoing surgery from May 2014 to August 2019 (n = 142) was done. Individualized risk calculation was obtained according to the available mortality risk scores: EuroScore I and II, PALSUSE, Risk-E, Costa, De Feo-Cotrufo, AEPEI, STS-risk, STS-IE, APORTEI, and ICE-PCS scores. A cross-validation analysis was performed on the score with the best area under the curve (AUC). The 30-day survival was 96.5% (95%CI 91-98%). The score with worse area under the curve (AUC = 0.6) was the STS-IE score, while the higher was for the RISK-E score (AUC = 0.89). The AUC of the majority of risk scores suggested acceptable performance; however, statistically significant differences in expected versus observed mortalities were common. The cross-validation analysis showed that a large number of survivors (> 75%) would not have been operated if arbitrary high-risk threshold estimates had been used to deny surgery. The observed mortality in our cohort is significantly lower than is predicted by contemporary risk scores. Despite the reasonable numeric performance of the analyzed scores, their utility in judging the operability of a given patient remains questionable, as demonstrated in the cross-validation analysis. Future guidelines may advise that denial of surgery should only follow a highly experienced Endocarditis Team evaluation.
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Procedimentos Cirúrgicos Cardíacos , Endocardite Bacteriana , Endocardite , Adulto , Humanos , Estudos de Coortes , Medição de Risco , Fatores de Risco , Endocardite/diagnóstico , Endocardite/cirurgia , Estudos RetrospectivosRESUMO
PURPOSE: The study aims to describe work status at diagnosis and 8 years post-diagnosis in a nationwide sample of breast cancer survivors (BCSs), and investigate associated and self-reported factors of reduced work status. METHODS: Women aged 20-65 years when diagnosed with stage I-III breast cancer (BC) in 2011 or 2012 were invited to participate in a questionnaire study in 2019 (n = 2803), of whom 49% (n = 1361) responded. For this sub-study, we included 974 BCSs below the legal retirement age in Norway (< 67 years) at survey and with complete work status data. Reduced work status was defined as being in paid work at BC diagnosis and not working at time of survey. Logistic regression analyses were applied to identify factors associated with reduced work status. RESULTS: Of BCSs who were in paid work at diagnosis (n = 845), 63% maintained their work status to 8 years later. Reduced work status was associated with not living with children (OR .44, 95% CI .24-.82), age (OR 1.16, 95% CI 1.11-1.21), chemotherapy (OR 2.83, 95% CI 1.24-6.61), > 2 comorbid conditions (OR 2.27, 95% CI 1.16-4.32), cognitive function (OR .99, 95% CI .98-.99), fatigue (OR 1.02, 95% CI 1.01-1.03), and neuroticism (OR 1.57, 95% CI 1.00-2.46). BC and late effects were reported as reasons for reduced work status and disability. CONCLUSIONS: The majority of BCSs who were in paid work at diagnosis were working 8 years later. IMPLICATIONS FOR CANCER SURVIVORS: Our results suggest a need to focus on fatigue and reduced cognitive function among long-term BCSs, with the ultimate aim of improving work sustainability.
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OBJECTIVE: Having a general practitioner in nursing homes during the pandemic by COVID-19 has allowed a multidisciplinary intervention to systematically review medication in institutionalized elderly patients; the objective of this study is to evaluate the impact of this intervention in reducing the number of drugs/patient. METHODS: A prospective multicenter study before-after of an intervention involving general practitioner and primare care pharmacists in 4 nursing homes of less than 50 residents. A review algorithm was used to identify Drug-Related Problems (DRPs) that were part of the primare care pharmacists recommendations. The degree of acceptance by the physician of these recommendations was measured. RESULTS: 121 patients reviewed with a mean age of 86.1 years (SD: 7.2); 87.6% were women. Of 98 patients analyzed, had an average of 9.4 (SD: 4.0) drugs/patient, was reduced by -1.6 [CI 95% -1.3 to -1.9] p<.001 after the intervention, the different was statistically significant. 409 DRPs were identified, an average of 4.2 per patient, who were part of a recommendation of which 316 (77.3%) were accepted. Most of the recommendations concerned deprescription or dose adjustment. Psycholeptics, antihypertensives and analgesics were the therapeutic groups most commonly involved in the detected DRPs. CONCLUSIONS: A statistically significant reduction in the mean number of drugs/patient following intervention has been observed. Many DRPs have been identified through the primare care pharmacists review, which have mostly been accepted by the physician.
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COVID-19 , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Casas de Saúde , Farmacêuticos , Estudos Prospectivos , SARS-CoV-2RESUMO
SUMMARY: Background. Aeroallergen selection for skin prick testing and the interpretation of results need to be in line with allergenic sources of a specific geographic area. Objective. To identify aeroallergens for a skin test panel for the specific geographical area of Istanbul in a multidisciplinary approach based on aerobiological parameters, cross-reactivity patterns and clinical symptoms. Methods. Aerobiological parameters, cross reactivity patterns and the European Standard Skin Prick Test Panel determined allergen selection. Atopic adult patients (n = 60) compiled a questionnaire and were skin prick tested with 29 aeroallergens. Aerobiological sampling followed the requirements of the European Aerobiology Society. Results were statistically analyzed. Results. 65% of patients had positive skin reactions. Sensitization to at least one grass allergen was 30%. Key grass allergens were timothy grass (Phleum pratense L.) 25.8% and Johnson grass (Sorghum halepense (L.) Pers.) 22.6%; correlations between grass-sensitizations were significant at p (minor) 0.01 and so was the correlation of Pooideae sensitization with symptoms and medication. Sensitization to at least one woody plant was 23%; to ash (Fraxinus excelsior L.) 8.1%; hazelnut (Corylus avellana L.), olive (Olea europaea L.) and mulberry (Morus alba L.) 6.5%; juniper (Juniperus ashei J.Buchholz) 4.8%. Correlations between Fagales allergen sensitizations were significant. Sensitization to at least one weed was 22%, sensitization to dock (Rumex crispus L.) 12.9%, ragweed (Ambrosia artemisiifolia L.), and mugwort (Artemisia vulgaris L.) 4.8%. Sensitization rates correlated significantly with the length of the Main Pollen Season. Conclusions. The European Standard Panel is suitable for the geographical area of Greater Istanbul, if it comprises Johnson grass and ash. Ragweed has become clinically relevant in this region. Mulberry and dock were exclusively associated to polysensitized individuals suggesting pan-allergen involvement.
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Alérgenos , Imunoglobulina E , Adulto , Humanos , Phleum , Pólen , Testes Cutâneos/métodosRESUMO
INTRODUCTION: Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability worldwide. Metabolic comorbidities such as type II diabetes occur with a higher rate in people with OA than in the general population. Several factors including obesity, hyperglycaemia toxicity and physical inactivity have been suggested as potential links between diabetes and OA, and have been shown to negatively impact patients' health and quality of life. However, little is known on the role of diabetes in determining the outcome of non-surgical and surgical management of OA, and at the same time, how different OA interventions may affect diabetes control. Thus, the overall aim of this project is to explore (1) the impact of diabetes on the outcome of non-surgical and surgical OA treatments and (2) the impact of non-surgical and surgical OA treatments on diabetes control. METHODS AND ANALYSIS: The study cohort is based on prospectively ascertained register data on a national level in Sweden. Data from OA patients who received a first-line non-surgical intervention and are registered in the National Quality Register for Better Management of Patients with Osteoarthritis will be merged with data from the Swedish Knee and Hip Arthroplasty Registers and the National Diabetes Register. Additional variables regarding patients' use of prescribed drugs, comorbidities, socioeconomic status and cause of death will be obtained through other national health and population data registers. The linkage will be performed on an individual level using unique personal identity numbers. ETHICS AND DISSEMINATION: This study received ethical approval (2019-02570) from the Swedish Ethical Review Authority. Results from this cohort will be submitted to peer-reviewed scientific journals and reported at the leading national and international meetings in the field.
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Diabetes Mellitus Tipo 2/complicações , Osteoartrite do Quadril/terapia , Osteoartrite do Joelho/terapia , Artroplastia de Quadril , Artroplastia do Joelho , Estudos de Coortes , Humanos , Síndrome Metabólica/complicações , Osteoartrite do Quadril/complicações , Osteoartrite do Joelho/complicações , Qualidade de Vida , Projetos de Pesquisa , Suécia , Resultado do TratamentoRESUMO
The European Commission Cooperation in Science and Technology (COST) Action FA1203 "SMARTER" aims to make recommendations for the sustainable management of Ambrosia across Europe and for monitoring its efficiency and cost-effectiveness. The goal of the present study is to provide a baseline for spatial and temporal variations in airborne Ambrosia pollen in Europe that can be used for the management and evaluation of this noxious plant. The study covers the full range of Ambrosia artemisiifolia L. distribution over Europe (39°N-60°N; 2°W-45°E). Airborne Ambrosia pollen data for the principal flowering period of Ambrosia (August-September) recorded during a 10-year period (2004-2013) were obtained from 242 monitoring sites. The mean sum of daily average airborne Ambrosia pollen and the number of days that Ambrosia pollen was recorded in the air were analysed. The mean and standard deviation (SD) were calculated regardless of the number of years included in the study period, while trends are based on those time series with 8 or more years of data. Trends were considered significant at p < 0.05. There were few significant trends in the magnitude and frequency of atmospheric Ambrosia pollen (only 8% for the mean sum of daily average Ambrosia pollen concentrations and 14% for the mean number of days Ambrosia pollen were recorded in the air). The direction of any trends varied locally and reflected changes in sources of the pollen, either in size or in distance from the monitoring station. Pollen monitoring is important for providing an early warning of the expansion of this invasive and noxious plant.
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The high-throughput department of DKMS Life Science Lab encounters novel human leukocyte antigen (HLA) alleles on a daily basis. To characterise these alleles, we have developed a system to sequence the whole gene from 5'- to 3'-UTR for the HLA loci A, B, C, DQB1 and DPB1 for submission to the European Molecular Biology Laboratory - European Nucleotide Archive (EMBL-ENA) and the IPD-IMGT/HLA Database. Our workflow is based on a dual redundant sequencing strategy. Using shotgun sequencing on an Illumina MiSeq instrument and single molecule real-time (SMRT) sequencing on a PacBio RS II instrument, we are able to achieve highly accurate HLA full-length consensus sequences. Remaining conflicts are resolved using the R package DR2S (Dual Redundant Reference Sequencing). Given the relatively high throughput of this strategy, we have developed the semi-automated web service TypeLoader, to aid in the submission of sequences to the EMBL-ENA and the IPD-IMGT/HLA Database. In the IPD-IMGT/HLA Database release 3.24.0 (April 2016; prior to the submission of the sequences described here), only 5.2% of all known HLA alleles have been fully characterised together with intronic and UTR sequences. So far, we have applied our strategy to characterise and submit 1056 HLA alleles, thereby more than doubling the number of fully characterised alleles. Given the increasing application of next generation sequencing (NGS) for full gene characterisation in clinical practice, extending the HLA database concomitantly is highly desirable. Therefore, we propose this dual redundant sequencing strategy as a workflow for submission of novel full-length alleles and characterisation of sequences that are as yet incomplete. This would help to mitigate the predominance of partially known alleles in the database.
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Alelos , Bases de Dados de Ácidos Nucleicos , Loci Gênicos , Antígenos HLA/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , HumanosAssuntos
Evolução Clonal , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/genética , Pré-Leucemia/genética , Adulto , Feminino , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Pré-Leucemia/tratamento farmacológico , Pré-Leucemia/terapia , Condicionamento Pré-Transplante , Sequenciamento do ExomaRESUMO
A method is presented, which allows quantification of the roughness of nonplanar boundaries of objects for which the neutral plane is not known. The method provides quantitative descriptions of both the local and global characteristics. How the method can be used to estimate the sizes of rough features and local curvatures is also presented. The potential of the method is illustrated by quantification of the roughness of two recrystallization boundaries in a pure Al specimen characterized by scanning electron microscopy.
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Regulatory T cell (Treg ) therapy has been exploited in autoimmune disease, solid organ transplantation and in efforts to prevent or treat graft-versus-host disease (GVHD). However, our knowledge on the in-vivo persistence of transfused Treg is limited. Whether Treg transfusion leads to notable changes in the overall Treg repertoire or whether longevity of Treg in the periphery is restricted to certain clones is unknown. Here we use T cell receptor alpha chain sequencing (TCR-α-NGS) to monitor changes in the repertoire of Treg upon polyclonal expansion and after subsequent adoptive transfer. We applied TCR-α-NGS to samples from two patients with chronic GVHD who received comparable doses of stem cell donor derived expanded Treg . We found that in-vitro polyclonal expansion led to notable repertoire changes in vitro and that Treg cell therapy altered the peripheral Treg repertoire considerably towards that of the infused cell product, to different degrees, in each patient. Clonal changes in the peripheral blood were transient and correlated well with the clinical parameters. We suggest that T cell clonotype analyses using TCR sequencing should be considered as a means to monitor longevity and fate of adoptively transferred T cells.
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Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas , Imunoterapia Adotiva/métodos , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Linfócitos T Reguladores/fisiologia , Proliferação de Células , Células Cultivadas , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Linfócitos T Reguladores/transplante , Transplante Homólogo , Resultado do TratamentoRESUMO
OBJECTIVE: Preoperative pain and function is viewed as an important predictor of total knee arthroplasty (TKA) outcomes. We examined whether variations in pain and function outcomes existed at 12 months between two centres in Sweden and Australia, and whether this was explained by variations in patient presentation for TKA. METHODS: This was a retrospective analysis of prospectively collected data. Patients from one centre in Australia (St. Vincent's Hospital (SVH), N = 516) and in Sweden (Trelleborg (TBG), N = 899) who underwent primary TKA between 2012 and 2013. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) was analysed pre- and 12 months' post TKA from which non-response to surgery was determined using the OMERACT-OARSI criteria. Multiple linear regression analysis was used to examine the relationship between change in pain and function and surgery centre, adjusting for preoperative patient characteristics and surgical technique. RESULTS: Despite worse preoperative outcomes in all subscales of the WOMAC for the SVH cohort, there were no clinically meaningful differences in 12-month WOMAC subscales nor change in WOMAC subscales between SVH and TBG. Almost identical proportions of patients were considered OMERACT-OARSI responders, 85.7% (SVH) and 85.9% (TBG), however for the SVH cohort 25 (4.9%) were moderate and 417 (80.8%) were high responders, compared to the TBG cohort of which 225 (25%) were moderate and 547 (60.9%) were high responders. CONCLUSION: Despite differences in preoperative presentation between 2 countries, improvements in pain and function and the proportion of individual who responded to TKA surgery at 1 year were similar. Factors related to poor response to TKA surgery require further elucidation.
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Artroplastia do Joelho , Osteoartrite do Joelho/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Austrália , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/cirurgia , Medição da Dor , Estudos Retrospectivos , Suécia , Resultado do TratamentoRESUMO
BACKGROUND: To date, most studies of the 'allergy epidemic' have been based on self-reported data. There is still limited knowledge on time trends in allergic sensitization, especially among adults. OBJECTIVE: To study allergic sensitization, its risk factors and time trends in prevalence. METHODS: Within West Sweden Asthma Study (WSAS), a population-based sample of 788 adults (17-60 years) underwent skin prick tests (SPTs) for 11 aeroallergens 2009-2012. Specific IgE was analysed in 750 of the participants. Those aged 20-46 years (n = 379) were compared with the European Community Respiratory Health Survey sample aged 20-46 year from the same area (n = 591) in 1991-1992. RESULTS: Among those aged 20-46 years, the prevalence of positive SPT to pollen increased, timothy from 17.1% to 29.0% (P < 0.001) and birch from 15.6% to 23.7% (P = 0.002) between 1991-1992 and 2009-2012. Measurements of specific IgE confirmed these increases. Prevalence of sensitization to all other tested allergens was unchanged. In the full WSAS sample aged 17-60 years, any positive SPT was seen in 41.9%, and the dominating sensitizers were pollen (34.3%), animals (22.8%) and mites (12.6%). Pollen sensitization was strongly associated with rhinitis, whereas indoor allergens were more associated with asthma. Growing up with livestock or furred pets decreased the risk of sensitization, adjusted odds ratio 0.53 (0.28-0.995) and 0.68 (0.47-0.98), respectively. CONCLUSION: Pollen sensitization has increased in Swedish adults since the early 1990s, while the prevalence of sensitization to other allergens has remained unchanged. This is one plausible explanation for the increase in rhinitis 1990-2008 in Swedish adults, during which time the prevalence of asthma, which is more associated with perennial allergens, was stable. Contact with animals in childhood seems to reduce the risk of sensitization well into adulthood. One major factor contributing to the rise in pollen allergy is a significant increase in levels of birch and grass pollen over the past three decades.
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Alérgenos/imunologia , Exposição Ambiental , Animais de Estimação/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/epidemiologia , Rinite Alérgica Sazonal/imunologia , Adolescente , Adulto , Animais , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Imunização , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Rinite Alérgica Sazonal/diagnóstico , Risco , Testes Cutâneos , Suécia/epidemiologia , Adulto JovemRESUMO
Background This study examined employment patterns and associated factors in lymphoma survivors treated with high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT) from diagnosis to a follow-up survey at a mean of 10 years after HDT-ASCT. Patients and methods All lymphoma survivors aged ≥18 years at HDT-ASCT in Norway from 1987 to 2008, and alive at the end of 2011 were eligible for this cross-sectional study performed in 2012/2013. Participants completed a mailed questionnaire. Job status was dichotomized as either employed (paid work) or not-employed (disability and retirement pension, on economic support, home-makers, or students). Results The response rate was 78%, and the sample (N = 312) contained 60% men. Mean age at HDT-ASCT was 44.3 and at survey 54.0 years. At diagnosis 85% of survivors were employed, 77% before and 77% after HDT-ASCT, and 58% at follow-up. Forty seven percent of the survivors were employed at all time points. The not-employed group at survey was significantly older and included significantly more females than the employed group. No significant between-group differences were observed for lymphoma-related variables. Fatigue, mental distress and type D personality were significantly higher among those not-employed, while quality of life was significantly lower compared to the employed group. Older age at survey, being female, work ability and presence of type D personality remained significantly related to being not-employed at survey in the multivariable analysis. Conclusions Our findings show that not-employed long-term survivors after HDT-ASCT for lymphoma have more comorbidity, cognitive problems and higher levels of anxiety/depression than employed survivors. These factors should be checked and eventually treated in order to improve work ability.
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Emprego/estatística & dados numéricos , Linfoma/epidemiologia , Sobreviventes/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Antineoplásicos/uso terapêutico , Comorbidade , Estudos Transversais , Feminino , Seguimentos , Humanos , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Qualidade de Vida , Estudos Retrospectivos , Fatores Sexuais , Transplante de Células-Tronco , Inquéritos e Questionários , Sobreviventes/psicologia , Transplante Autólogo , Resultado do Tratamento , Desemprego/estatística & dados numéricosRESUMO
OBJECTIVE: To compare perioperative and clinico-pathological outcomes of patients with early-stage cervical cancer who underwent robot-assisted radical hysterectomy (RRH) and open radical hysterectomy (ORH). METHODS: This retrospective multi-center study abstracted demographic, clinico-pathological and perioperative outcomes data from medical records of 491 cervical cancer patients treated with RRH (n = 259) ORH (n = 232) between 2005 and 2011 at two American and one Norwegian University Cancer Centres. RESULTS: Mean estimated blood loss (EBL) and transfusion rates were less for RRH than for ORH (97 vs. 49 mL, p < 0.001, and 3% vs. 7%, p = 0.018, respectively). Mean length of hospital stay (LOS) was significantly shorter in RRH versus ORH (1.8 vs. 5.1 days, p < 0.001). Mean operative time was longer for RRH than ORH (220 vs. 156 min, p < 0.001). Although overall complications were similar (p = 0.49), intra-operative complications were less common in the RRH group than ORH (4% vs. 10%, p = 0.004). In multivariate regression analyses longer operative time, less EBL and intra-operative complications, shorter LOS, and more pre-operative cone were significantly associated with RRH versus ORH. Recurrence and death rates were not statistically different for the two groups at a mean follow-up time of 39 months (p = 1.00 and p = 0.48, respectively). CONCLUSIONS: RRH had improved clinical outcomes compared to ORH in the treatment of early-stage cervical cancer in terms of EBL, intra-operative complications, transfusion rates, LOS, and pre-operative cone. Disease recurrence and survival were comparable for the two procedures.
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Histerectomia/métodos , Estadiamento de Neoplasias , Robótica/métodos , Neoplasias do Colo do Útero/cirurgia , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Noruega/epidemiologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia , Neoplasias do Colo do Útero/diagnósticoRESUMO
Allogeneic stem cell transplantation is potentially curative, but associated with post-transplantation complications, including cytomegalovirus (CMV) infections. An effective immune response requires T cells recognizing CMV epitopes via their T cell receptors (TCRs). Little is known about the TCR repertoire, in particular the TCR-α repertoire and its clinical relevance in patients following stem cell transplantation. Using next-generation sequencing we examined the TCR-α repertoire of CD8(+) T cells and CMV-specific CD8(+) T cells in four patients. Additionally, we performed single-cell TCR-αß sequencing of CMV-specific CD8(+) T cells. The TCR-α composition of human leucocyte antigen (HLA)-A*0201 CMVpp65- and CMVIE -specific T cells was oligoclonal and defined by few dominant clonotypes. Frequencies of single clonotypes reached up to 11% of all CD8(+) T cells and half of the total CD8(+) T cell repertoire was dominated by few CMV-reactive clonotypes. Some TCR-α clonotypes were shared between patients. Gene expression of the circulating CMV-specific CD8(+) T cells was consistent with chronically activated effector memory T cells. The CD8(+) T cell response to CMV reactivation resulted in an expansion of a few TCR-α clonotypes to dominate the CD8(+) repertoires. These results warrant further larger studies to define the ability of oligoclonally expanded T cell clones to achieve an effective anti-viral T cell response in this setting.
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Antígenos Virais/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Epitopos/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Idoso , Sequência de Aminoácidos , Antígenos Virais/genética , Linfócitos T CD8-Positivos/patologia , Linfócitos T CD8-Positivos/virologia , Células Clonais , Citomegalovirus/crescimento & desenvolvimento , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/virologia , Epitopos/genética , Feminino , Regulação da Expressão Gênica , Antígeno HLA-A2/genética , Antígeno HLA-A2/imunologia , Humanos , Memória Imunológica , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Linfocítica Crônica de Células B/terapia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Análise de Sequência de DNA , Transdução de Sinais , Análise de Célula Única , Transplante HomólogoRESUMO
The ability of proteins to sense membrane tension is pervasive in biology. A higher-resolution structure of the Escherichia coli small-conductance mechanosensitive channel MscS identifies alkyl chains inside pockets formed by the transmembrane helices (TMs). Purified MscS contains E. coli lipids, and fluorescence quenching demonstrates that phospholipid acyl chains exchange between bilayer and TM pockets. Molecular dynamics and biophysical analyses show that the volume of the pockets and thus the number of lipid acyl chains within them decreases upon channel opening. Phospholipids with one acyl chain per head group (lysolipids) displace normal phospholipids (with two acyl chains) from MscS pockets and trigger channel opening. We propose that the extent of acyl-chain interdigitation in these pockets determines the conformation of MscS. When interdigitation is perturbed by increased membrane tension or by lysolipids, the closed state becomes unstable, and the channel gates.
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Proteínas de Escherichia coli/metabolismo , Escherichia coli/fisiologia , Canais Iônicos/metabolismo , Mecanotransdução Celular , Fosfolipídeos/metabolismo , Fenômenos Biofísicos , Cristalografia por Raios X , Escherichia coli/química , Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/isolamento & purificação , Canais Iônicos/química , Canais Iônicos/isolamento & purificação , Modelos Moleculares , Simulação de Dinâmica Molecular , Conformação ProteicaRESUMO
We identified a group of patients from the Swedish Arthroplasty Register who reported no relief of pain or worse pain one year after a total knee replacement (TKR). A total of two different patient-reported pain scores were used during this process. We then evaluated how the instruments used to measure pain affected the number of patients who reported no relief of pain or worse pain, and the relative effect of potential risk factors. Between 2008 and 2010, 2883 TKRs were performed for osteoarthritis in two Swedish arthroplasty units. After applying exclusion criteria, 2123 primary TKRs (2123 patients) were included in the study. The Knee injury and Osteoarthritis Outcome Score (KOOS) and a Visual Analogue Scale (VAS) for knee pain were used to assess patients pre-operatively and one year post-operatively. Only 50 of the 220 patients (23%) who reported no pain relief on either the KOOS pain subscale or the VAS for knee pain did so with both of these instruments. Patients who reported no pain relief on either measure tended to have less pain pre-operatively but a higher degree of anxiety. Charnley category C was a predictor for not gaining pain relief as measured on a VAS for knee pain. The number of patients who are not relieved of pain after a TKR differs considerably depending on the instrument used to measure pain.
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Artroplastia do Joelho , Dor Musculoesquelética/diagnóstico , Osteoartrite do Joelho/cirurgia , Medição da Dor/métodos , Dor Pós-Operatória/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/epidemiologia , Dor Musculoesquelética/etiologia , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Modelos de Riscos Proporcionais , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do TratamentoRESUMO
We are entering a new era with governmental bodies taking an increasingly guiding role, gaining control of registries, demanding direct access with release of open public information for quality comparisons between hospitals. This review is written by physicians and scientists who have worked with the Swedish Knee Arthroplasty Register (SKAR) periodically since it began. It reviews the history of the register and describes the methods used and lessons learned. Cite this article: Bone Joint Res 2014;3:217-22.
RESUMO
BACKGROUND: Although the negative consequences on health of being obese are well known, most adults gain weight across the lifespan. The general increase in body mass index (BMI) is mainly considered to originate from behavioral and environmental changes; however, few studies have evaluated the influence of these factors on change in BMI in the presence of genetic risk. We aimed to study the influence of multifactorial causes of change in BMI, over 65 years. METHODS AND FINDINGS: Totally, 6130 participants from TwinGene, who had up to five assessments, and 536 from the Swedish Adoption/Twin Study of Aging, who had up to 12 assessments, ranging over 65 years were included. The influence of lifestyle factors, birth cohort, cardiometabolic diseases and an individual obesity genetic risk score (OGRS) based on 32 single nucleotide polymorphisms on change in BMI was evaluated with a growth model. For both sexes, BMI increased from early adulthood to age of 65 years, after which the increase leveled off; BMI declined after age of 80 years. A higher OGRS, birth after 1925 and cardiometabolic diseases were associated with higher average BMI and a steeper increase in BMI prior to 65 years of age. Among men, few factors were identified that influence BMI trajectories in late life, whereas for women type 2 diabetes mellitus and dementia were associated with a steeper decrease in BMI after the age of 65 years. CONCLUSIONS: There are two turning points in BMI in late adulthood, one at the age of 65 years and one at the age 80 years. Factors associated with an increase in BMI in midlife were not associated with an increase in BMI after the age of 65 years. These findings indicate that the causes and consequences of change in BMI differ across the lifespan. Current health recommendations need to be adjusted accordingly.