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BACKGROUND: The role of consolidation radiotherapy in primary mediastinal B-cell lymphoma (PMBCL) patients is controversial. METHODS: The IELSG37 trial, a randomized non-inferiority study, aimed to assess whether irradiation can be omitted in PMBCL patients with complete metabolic response (CMR) after induction immunochemotherapy. Primary endpoint was progression-free survival (PFS) at 30 months post-randomization. Patients with CMR were randomly assigned to observation or consolidation radiotherapy (30 Gy). With a non-inferiority margin of 10% (assuming a 30-month PFS of 85% in both arms), a sample size of 540 patients was planned with 376 expected to be randomized. RESULTS: The observed events were considerably lower than expected, therefore, primary endpoint analysis was conducted when ≥95% of patients were followed for ≥30 months. Of 545 patients enrolled, 268 were in CMR after induction and were randomized to observation (n=132) or radiotherapy (n=136). The 30-month PFS was 96.2% in the observation arm and 98.5% in the radiotherapy arm, with a stratified hazard ratio of 1.47 (95%CI, 0.34 to 6.28) and absolute risk difference of 0.68% (95%CI, -0.97% to 7.46%). The 5-year overall survival was 99% in both arms.Non-randomized patients were managed according to local policies. Radiotherapy was the only treatment in 86% of those with Deauville score (DS) 4 and in 57% of those with DS 5. The 5-year PFS and OS of patients with DS 4 (95.8% and 97.5%, respectively) were not significantly different from those of randomized patients. Patients with DS5 had significantly poorer 5-year PFS and OS (60.3% and 74.6%, respectively). CONCLUSIONS: This study, the largest randomized trial of radiotherapy in PMBCL, demonstrated favorable outcomes in patients achieving CMR with no survival impairment for those omitting irradiation.
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BACKGROUND: Radical gastrectomy remains the main treatment for gastric cancer, despite its high mortality. A clinical predictive model of 90-day mortality (90DM) risk after gastric cancer surgery based on the Spanish EURECCA registry database was developed using a matching learning algorithm. We performed an external validation of this model based on data from an international multicenter cohort of patients. METHODS: A cohort of patients from the European GASTRODATA database was selected. Demographic, clinical, and treatment variables in the original and validation cohorts were compared. The performance of the model was evaluated using the area under the curve (AUC) for a random forest model. RESULTS: The validation cohort included 2546 patients from 24 European hospitals. The advanced clinical T- and N-category, neoadjuvant therapy, open procedures, total gastrectomy rates, and mean volume of the centers were significantly higher in the validation cohort. The 90DM rate was also higher in the validation cohort (5.6%) vs. the original cohort (3.7%). The AUC in the validation model was 0.716. CONCLUSION: The externally validated model for predicting the 90DM risk in gastric cancer patients undergoing gastrectomy with curative intent continues to be as useful as the original model in clinical practice.
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Aims: Shoulder arthroplasty is effective in the management of end-stage glenohumeral joint arthritis. However, it is major surgery and patients must balance multiple factors when considering the procedure. An understanding of patients' decision-making processes may facilitate greater support of those considering shoulder arthroplasty and inform the outcomes of future research. Methods: Participants were recruited from waiting lists of three consultant upper limb surgeons across two NHS hospitals. Semi-structured interviews were conducted with 12 participants who were awaiting elective shoulder arthroplasty. Transcribed interviews were analyzed using a grounded theory approach. Systematic coding was performed; initial codes were categorized and further developed into summary narratives through a process of discussion and refinement. Data collection and analyses continued until thematic saturation was reached. Results: Two overall categories emerged: the motivations to consider surgery, and the information participants used to inform their decision-making. Motivations were, broadly, the relief of pain and the opportunity to get on with life and regain independence. When participants' symptoms and restrictions prevented them enjoying life to a sufficient extent, this provided the motivation to proceed with surgery. Younger participants tended to focus on maintaining employment and recreational activities, and older patients were eager to make the most of their remaining lifetime. Participants gathered information from a range of sources and were keen to optimize their recovery where possible. An important factor for participants was whether they trusted their surgeon and were prepared to delegate responsibility for elements of their care. Conclusion: Relief of pain and the opportunity to get on with life were the primary reasons to undergo shoulder arthroplasty. Participants highlighted the importance of the patient-surgeon relationship and the need for accurate information in an accessible format which is relevant to people of different ages and functional demands.
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BACKGROUND: Dislocated IOL exchange conventionally involves manipulation within the anterior chamber which risks secondary injury to anterior chamber structures. We describe and evaluate a 4-haptic IOL rescue technique that avoids entering the anterior chamber and thus minimizes post operative inflammation, astigmatism and recovery time relative to conventional IOL explantation and replacement techniques. METHODS: Retrospective, non-randomized, interventional study of all patients undergoing 4-haptic IOL rescue performed by two independent vitreoretinal surgeons at a single UK centre over two years. SURGICAL TECHNIQUE: A limited peritomy is performed with four 25-gauge scleral ports placed to enable use of two forceps, an infusion and a chandelier. A further four 27-gauge sclerotomies are symmetrically placed on the nasal and temporal sclera at 3 mm from the limbus with a 5 mm vertical separation on either side. A pars plana vitrectomy is performed followed by chandelier illuminated, bimanual cleaning of the dislocated IOL using 27-gauge serrated forceps. Gore-tex sutures are threaded through the IOL islets within the vitreous cavity and externalized through the sclerotomies for scleral re-fixation followed by conjunctival closure. RESULTS: Seven patients underwent IOL recycling with Gore-Tex suture scleral re-fixation. All procedures were successful in repositioning the IOLs, with all patients satisfied with post-operative outcome. Mean (standard deviation) time to IOL dislocation was 13 (3) years. Median visual acuity significantly improved post-operatively from 0.85 logMAR (Interquartile Range [IQR]: 0.2-2.1) to 0.07 (0.02-0.60) logMAR (p = 0.02). No significant post-operative complications were noted apart from persistent cystoid macular oedema in one patient non-compliant with post-operative treatment. CONCLUSIONS: Transscleral refixation using Gore-Tex suture is an effective, safe and practical approach in the management of dislocated 4-piece IOLs.
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BACKGROUND: Clinicians regularly prescribe opioids to manage acute and chronic cancer pain, frequently to address acute postoperative pain, and occasionally to manage chronic non-cancer pain. Clinical efficacy may be suboptimal in some patients due to side effects and/or poor response, and opioid rotation/switching (conversions) is frequently necessary. Despite the widespread practice, opioid conversion ratios are inconsistent between clinicians, practices, and countries. Therefore, we performed a scoping systematic review of opioid conversion studies to inform an international eDelphi guideline. METHODS: To ensure a comprehensive review, we conducted a systematic search across multiple databases (OVID Medline, PsycINFO, Embase, EBM-Cochrane Database of Systematic Reviews and Registered Trials, LILACS, IMEMR, AIM, WPRIM) using studies published up to June 2022. Additionally, we performed hand and Google Scholar searches to verify the completeness of our findings. Our inclusion criteria encompassed randomized and non-randomized studies with no age limit, with only a few pediatric studies identified. We included studies on cancer, non-cancer, acute, and chronic pain. The level and grade of evidence were determined based on the Multinational Supportive Care in Cancer (MASCC) criteria. RESULTS: Our search yielded 21,118 abstracts, including 140 randomized (RCT) and 68 non-randomized (NRCT) clinical trials. We compared these results with recently published conversion ratios. Modest correlations were noted between published reviews and the present scoping systematic review. CONCLUSION: The present scoping systematic review found low-quality evidence to support an opioid conversion guideline. We will use these data, including conversion ratios and type and route of administration, to inform an eDelphi guideline.
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Analgésicos Opioides , Dolor en Cáncer , Humanos , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Dolor en Cáncer/tratamiento farmacológico , Dolor Crónico/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Relación Dosis-Respuesta a Droga , Dolor Agudo/tratamiento farmacológicoRESUMEN
Methane is a powerful greenhouse gas, more potent than carbon dioxide, and emitted from a variety of natural sources including wetlands, permafrost, mammalian guts and termites. As increases in global temperatures continue to break records, quantifying the magnitudes of key methane sources has never been more pertinent. Over the last 40 years, the contribution of termites to the global methane budget has been subject to much debate. The most recent estimates of termite emissions range between 9 and 15 Tg CH4 year-1, approximately 4% of emissions from natural sources (excluding wetlands). However, we argue that the current approach for estimating termite contributions to the global methane budget is flawed. Key parameters, namely termite methane emissions from soil, deadwood, living tree stems, epigeal mounds and arboreal nests, are largely ignored in global estimates. This omission occurs because data are lacking and research objectives, crucially, neglect variation in termite ecology. Furthermore, inconsistencies in data collection methods prohibit the pooling of data required to compute global estimates. Here, we summarise the advances made over the last 40 years and illustrate how different aspects of termite ecology can influence the termite contribution to global methane emissions. Additionally, we highlight technological advances that may help researchers investigate termite methane emissions on a larger scale. Finally, we consider dynamic feedback mechanisms of climate warming and land-use change on termite methane emissions. We conclude that ultimately the global contribution of termites to atmospheric methane remains unknown and thus present an alternative framework for estimating their emissions. To significantly improve estimates, we outline outstanding questions to guide future research efforts.
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Isópteros , Metano , Isópteros/fisiología , Isópteros/metabolismo , Metano/análisis , Metano/metabolismo , Animales , Cambio Climático , Gases de Efecto Invernadero/análisisRESUMEN
PURPOSE: Many patients living beyond cancer experience significant unmet needs, although few of these patients are currently reviewed by specialist palliative care teams (SPCTs). The aim of this narrative review was to explore the current and potential role of SPCTs in this cohort of patients. METHODS: A search strategy was developed for Medline, and adapted for Embase, CINAHL, and PsycInfo. Additionally, websites of leading oncology, cancer survivorship, and specialist palliative care organisations were examined. The focus of the search was on individuals living beyond cancer rather than other groups of cancer survivors. RESULTS: 111 articles were retrieved from the search for full text review, and 101 other sources of information were identified after hand searching the reference lists of the full text articles, and the aforesaid websites. The themes of the review encompass the definition of palliative care/specialist palliative care, current models of specialist palliative care, core activities of SPCTs, relevant expertise of SPCTs, and potential barriers to change in relation to extending their support and expertise to individuals living beyond cancer. The review identified a paucity of evidence to support the role of SPCTs in the management of patients living beyond cancer. CONCLUSIONS: Individuals living beyond cancer have many unmet needs, and specific services are required to manage these problems. Currently, there is limited evidence to support the role of specialist palliative care teams in the management of this cohort of people, and several potential barriers to greater involvement, including limited resources, and lack of relevant expertise.
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Cuidados Paliativos , Humanos , Cuidados Paliativos/métodos , Cuidados Paliativos/organización & administración , Supervivientes de Cáncer/psicología , Neoplasias/terapia , Grupo de Atención al Paciente/organización & administraciónRESUMEN
PURPOSE: Audible upper airway secretions ("death rattle") is a common problem in cancer patients at the end-of-life. However, there is little information about its clinical features. METHODS: This is a secondary analysis of a cluster randomised trial of clinically-assisted hydration in cancer patients in the last days of life. Patients were assessed 4 hourly for end-of-life problems (including audible secretions), which were recorded as present or absent, excepting restlessness/agitation, which was scored using the modified Richmond Agitation and Sedation Scale. Patients were followed up until death. RESULTS: 200 patients were recruited, and 186 patients died during the study period. Overall, 54.5% patients developed audible secretions at some point during the study, but only 34.5% patients had audible secretions at the time of death. The prevalence of audible secretions increased the closer to death, with a marked increase in the last 12-16 h of life (i.e. the prevalence of audible secretions was highest at the time of death). Of those with audible secretions at the time of death, 24 had had a previous episode that had resolved. Development of audible secretions was not associated with use of clinically-assisted hydration, but there was an association between audible secretions and restlessness/agitation, and audible secretions and pain. However, most patients with audible secretions were not restless/agitated, or in pain, when assessed. CONCLUSION: Audible secretions ("death rattle") are common in cancer patients at the end-of-life, but their natural history is extremely variable, with some patients experiencing multiple episodes during the terminal phase (although not necessarily experiencing an episode at the time of death).
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Neoplasias , Cuidado Terminal , Humanos , Masculino , Femenino , Anciano , Cuidado Terminal/métodos , Persona de Mediana Edad , Anciano de 80 o más Años , Factores de Tiempo , Adulto , Fluidoterapia/métodos , Secreciones CorporalesRESUMEN
The incidence of gastric cancer (GC) is expected to increase to 1.77 million cases by 2040. To improve treatment outcomes, GC patients are increasingly treated with neoadjuvant chemotherapy (NAC) prior to curative-intent resection. Although NAC enhances locoregional control and comprehensive patient care, survival rates remain poor, and further investigations should establish outcomes assessment of current clinical pathways. Individually assessed parameters have served as benchmarks for treatment quality in the past decades. The Outcome4Medicine Consensus Conference underscores the inadequacy of isolated metrics, leading to increased recognition and adoption of composite measures. One of the most simple and comprehensive is the "All or None" method, which refers to an approach where a specific set of criteria must be fulfilled for an individual to achieve the overall measure. This narrative review aims to present the rationale for the implementation of a novel composite measure, Textbook Neoadjuvant Outcome (TNO). TNO integrates five objective and well-established components: Treatment Toxicity, Laboratory Tests, Imaging, Time to Surgery, and Nutrition. It represents a desired, multidisciplinary care and hospitalization of GC patients undergoing NAC to identify the treatment- and patient-related data required to establish high-quality oncological care further. A key strength of this narrative review is the clinical feasibility and research background supporting the implementation of the first and novel composite measure representing the "ideal" and holistic care among patients with locally advanced esophago-gastric junction (EGJ) and GC in the preoperative period after NAC. Further analysis will correlate clinical outcomes with the prognostic factors evaluated within the TNO framework.
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ABSTRACT: Posttransplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation, and cytotoxic chemotherapy is associated with treatment-related morbidity and mortality. Current treatment takes a sequential, risk-stratified approach, and patients with low-risk disease after initial immunotherapy can avoid escalation to immunochemotherapy. TIDaL is a prospective, single-arm phase 2 trial investigating the activity and tolerability of ibrutinib combined with risk-stratified therapy for first-line treatment of PTLD. Eligible patients were adults with newly diagnosed CD20+ B-cell PTLD after solid organ transplant and performance status 0 to 2. Initial treatment comprised 49 days of ibrutinib 560 mg once daily, with 4 doses of weekly rituximab. Treatment response on interim scan and baseline International Prognostic Index were used to allocate patients to either a low-risk arm (who continued ibrutinib, alongside 4 further doses of 3-weekly rituximab) or high-risk (escalation to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] immunochemotherapy, with ibrutinib continuing in patients aged <65 years). The primary outcome was complete response on interim scan, achieved by 11 of 38 patients (29%; 95% confidence interval [CI], 15-46). This did not reach the prespecified threshold for clinically significant activity. Secondary outcomes included allocation to the low-risk arm (41% of patients), 2-year progression-free survival (58%; 95% CI, 44-76), and 2-year overall survival (76%; 95% CI, 63-91). Adverse events were mostly hematological, gastrointestinal, and infective. Although TIDaL does not support adding ibrutinib into first-line treatment of PTLD, increasing the proportion of patients who can be treated without cytotoxic chemotherapy remains an important aim of future research. This trial was registered at www.clinicaltrials.gov as #ISRCTN32667607.
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Adenina , Protocolos de Quimioterapia Combinada Antineoplásica , Trastornos Linfoproliferativos , Piperidinas , Rituximab , Humanos , Piperidinas/uso terapéutico , Piperidinas/efectos adversos , Piperidinas/administración & dosificación , Persona de Mediana Edad , Femenino , Masculino , Adenina/análogos & derivados , Adenina/uso terapéutico , Trastornos Linfoproliferativos/tratamiento farmacológico , Trastornos Linfoproliferativos/etiología , Anciano , Adulto , Rituximab/efectos adversos , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trasplante de Órganos/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Ciclofosfamida/efectos adversos , Vincristina/administración & dosificación , Vincristina/efectos adversos , Vincristina/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Prednisona/administración & dosificación , Prednisona/efectos adversos , Prednisona/uso terapéutico , Estudios Prospectivos , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Pirazoles/administración & dosificaciónRESUMEN
Aims: Metal and ceramic humeral head bearing surfaces are available choices in anatomical shoulder arthroplasties. Wear studies have shown superior performance of ceramic heads, however comparison of clinical outcomes according to bearing surface in total shoulder arthroplasty (TSA) and hemiarthroplasty (HA) is limited. This study aimed to compare the rates of revision and reoperation following metal and ceramic humeral head TSA and HA using data from the National Joint Registry (NJR), which collects data from England, Wales, Northern Ireland, Isle of Man and the States of Guernsey. Methods: NJR shoulder arthroplasty records were linked to Hospital Episode Statistics and the National Mortality Register. TSA and HA performed for osteoarthritis (OA) in patients with an intact rotator cuff were included. Metal and ceramic humeral head prostheses were matched within separate TSA and HA groups using propensity scores based on 12 and 11 characteristics, respectively. The primary outcome was time to first revision and the secondary outcome was non-revision reoperation. Results: A total of 4,799 TSAs (3,578 metal, 1,221 ceramic) and 1,363 HAs (1,020 metal, 343 ceramic) were included. The rate of revision was higher for metal compared with ceramic TSA, hazard ratio (HR) 3.31 (95% confidence interval (CI) 1.67 to 6.58). At eight years, prosthesis survival for ceramic TSA was 98.7% (95% CI 97.3 to 99.4) compared with 96.4% (95% CI 95.2 to 97.3) for metal TSA. The majority of revision TSAs were for cuff insufficiency or instability/dislocation. There was no significant difference in the revision rate for ceramic compared with metal head HA (HR 1.33 (95% CI 0.76 to 2.34)). For ceramic HA, eight-year prosthetic survival was 92.8% (95% CI 86.9 to 96.1), compared with 91.6% (95% CI 89.3 to 93.5) for metal HA. The majority of revision HAs were for cuff failure. Conclusion: The rate of all-cause revision was higher following metal compared with ceramic humeral head TSA in patients with OA and an intact rotator cuff. There was no difference in the revision rate for HA according to bearing surface.
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Artroplastía de Reemplazo de Hombro , Cerámica , Hemiartroplastia , Diseño de Prótesis , Falla de Prótesis , Reoperación , Prótesis de Hombro , Humanos , Reoperación/estadística & datos numéricos , Hemiartroplastia/métodos , Masculino , Femenino , Artroplastía de Reemplazo de Hombro/métodos , Anciano , Persona de Mediana Edad , Osteoartritis/cirugía , Sistema de Registros , Cabeza Humeral/cirugía , Anciano de 80 o más Años , MetalesRESUMEN
PURPOSE: The provision of clinically assisted hydration (CAH) in patients with advanced cancer is controversial, and there is a paucity of specific guidance and so a diversity in clinical practice. Consequently, the Palliative Care Study Group of the Multinational Association of Supportive Care in Cancer (MASCC) formed a sub-group to develop evidence-based guidance on the use of CAH in patients with advanced cancer. METHODS: This guidance was developed in accordance with the MASCC Guidelines Policy. A search strategy for Medline was developed, and the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were explored for relevant reviews/trials, respectively. RESULTS: Due to the paucity of evidence, the sub-group was not able to develop a prescribed guideline, but was able to generate a number of "expert opinion statements": these statements relate to assessment of patients, indications for CAH, contraindications for CAH, procedures for initiating CAH, and reassessment of patients. CONCLUSIONS: This guidance provides a framework for the use of CAH in advanced cancer, although every patient requires individualised management.
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Fluidoterapia , Neoplasias , Cuidados Paliativos , Humanos , Neoplasias/terapia , Neoplasias/complicaciones , Cuidados Paliativos/métodos , Fluidoterapia/métodosRESUMEN
BACKGROUND: We have previously reported our experience of the effect of complete excision of Hoffa's fat pad on patella height post TKR. In this study, we compared the change of patellar height post TKR before and after the senior author changed his practice to preserving Hoffa's fat pad. METHODS: This was a retrospective analysis of a prospective series of TKRs performed or directly supervised by the senior author. In Group 1 were 72 patients performed before April 2011 who had complete excision of Hoffa's fat pad to maximise exposure during the procedure. In Group 2 were 138 patients performed after April 2011 who had the minimum excision of Hoffa's fat pad to allow adequate surgical exposure. The surgical technique and rehabilitation protocol were identical in all other respects. Patellar height was assessed using the Caton-Deschamps Index both immediately postoperative and at a minimum follow up of 1 year. RESULTS: Group 1 included 28 males, 44 females with mean age 68.36 years. The mean CDI in this group changed from 0.54 immediately post-operatively to 0.46 at minimum one year follow-up (P = 0.001) indicating progressive patella baja. Group 2 included 56 males, 82 females with mean age 65 years. The mean CDI changed from 0.67 immediately post-operative to 0.68 at minimum one year post follow-up (P = 0.32) indicating no statistically or clinically relevant post-operative change in patellar height. CONCLUSION: Total excision of Hoffa's fat pad is associated with progressive post-operative patella baja. This can be avoided by resecting the minimum amount of fat pad to allow adequate exposure during the procedure.
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Tejido Adiposo , Artroplastia de Reemplazo de Rodilla , Rótula , Humanos , Masculino , Femenino , Rótula/cirugía , Anciano , Estudios Retrospectivos , Artroplastia de Reemplazo de Rodilla/métodos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Persona de Mediana Edad , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Total shoulder arthroplasty (TSA) and hemiarthroplasty (HA) are used in the management of end-stage glenohumeral arthritis. Improvement in shoulder function and resolution of symptoms are high priorities for patients. The aim of this study was to compare patient-reported outcome measures (PROMs) following TSA and HA. METHODS: Records from the National Joint Registry of England, Wales, Northern Ireland, and the Isle of Man were linked to the PROMs data set. The study included anatomic shoulder arthroplasties performed for osteoarthritis in patients with an intact rotator cuff. Patients with preoperative and postoperative Oxford Shoulder Scores (OSSs) were included. The improvement in OSS at 6 months and 5 years and the trend in scores over time were analyzed for each prosthesis. A cohort of 2002 patients were matched on 10 variables using propensity scores. OSSs at 6 months following TSA vs. HA were compared in the matched sample. RESULTS: There was a significant improvement in the OSS in both groups (P < .001). At 6 months, the OSSs were superior following TSA compared with HA (median 42 vs. 36, P < .001). The median score at 5 years was 44 following TSA and 35 following HA. Score distributions were skewed toward the maximum score. The highest possible score (48) was achieved in 28% (134 of 478) of TSAs and 9% (20 of 235) of HAs at 5 years. The improvement in the preoperative to 6-month OSS reached the minimal clinically important difference of 5.5 in 92% (1653 of 1792) of TSAs and in 80% (416 of 523) of HAs. At 5 years, this improvement was maintained in 91% (339 of 374) of TSAs and 78% (136 of 174) of HAs. CONCLUSION: TSA resulted in superior OSSs at 6 months in patients with osteoarthritis. The median OSS improved from 6 months to 5 years following TSA; however, there was a small decline in scores following HA. A ceiling effect was shown in the OSS following TSA at 5 years.
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OBJECTIVE: High-fat diets cause obesity in male mice; however, the underlying mechanisms remain controversial. Here, three contrasting ideas were assessed: hedonic overdrive, reverse causality, and passive overconsumption models. METHODS: A total of 12 groups of 20 individually housed 12-week-old C57BL/6 male mice were exposed to 12 high-fat diets with varying fat content from 40% to 80% (by calories), protein content from 5% to 30%, and carbohydrate content from 8.4% to 40%. Body weight and food intake were monitored for 30 days after 7 days at baseline on a standard low-fat diet. RESULTS: After exposure to the diets, energy intake increased first, and body weight followed later. Intake then declined. The peak energy intake was dependent on both dietary protein and carbohydrate, but not the dietary fat and energy density, whereas the rate of decrease in intake was only related to dietary protein. On high-fat diets, the weight of food intake declined, but despite this average reduction of 14.4 g in food intake, they consumed, on average, 357 kJ more energy than at baseline. CONCLUSIONS: The hedonic overdrive model fit the data best. The other two models were not supported.
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Dieta Alta en Grasa , Carbohidratos de la Dieta , Masculino , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Carbohidratos de la Dieta/metabolismo , Ratones Endogámicos C57BL , Obesidad/etiología , Obesidad/metabolismo , Grasas de la Dieta/metabolismo , Ingestión de Energía , Proteínas en la DietaRESUMEN
MYC translocation occurs in 8-14% of diffuse large B-cell lymphoma (DLBCL), and may concur with BCL2 and/or BCL6 translocation, known as double-hit (DH) or triple-hit (TH). DLBCL-MYC/BCL2-DH/TH are largely germinal centre B-cell like subtype, but show variable clinical outcome, with IG::MYC fusion significantly associated with inferior survival. While DLBCL-MYC/BCL6-DH are variable in their cell-of-origin subtypes and clinical outcome. Intriguingly, only 40-50% of DLBCL with MYC translocation show high MYC protein expression (>70%). We studied 186 DLBCLs with MYC translocation including 32 MYC/BCL2/BCL6-TH, 75 MYC/BCL2-DH and 26 MYC/BCL6-DH. FISH revealed a MYC/BCL6 fusion in 59% of DLBCL-MYC/BCL2/BCL6-TH and 27% of DLBCL-MYC/BCL6-DH. Targeted NGS showed a similar mutation profile and LymphGen genetic subtype between DLBCL-MYC/BCL2/BCL6-TH and DLBCL-MYC/BCL2-DH, but variable LymphGen subtypes among DLBCL-MYC/BCL6-DH. MYC protein expression is uniformly high in DLBCL with IG::MYC, but variable in those with non-IG::MYC including MYC/BCL6-fusion. Translocation breakpoint analyses of 8 cases by TLC-based NGS showed no obvious genomic configuration that enables MYC transactivation in 3 of the 4 cases with non-IG::MYC, while a typical promoter substitution or IGH super enhancer juxtaposition in the remaining cases. The findings potentially explain variable MYC expression in DLBCL with MYC translocation, and also bear practical implications in its routine assessment.
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Linfoma de Células B Grandes Difuso , Humanos , Activación Transcripcional , Proteínas Proto-Oncogénicas c-bcl-6/genética , Linfoma de Células B Grandes Difuso/patología , Translocación Genética , Genómica , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismoRESUMEN
BACKGROUND AND PURPOSE: Total shoulder arthroplasty (TSA) and hemiarthroplasty (HA) are used in the management of osteoarthritis of the glenohumeral joint. We aimed to determine whether TSA or HA resulted in a lower risk of adverse outcomes in patients of all ages with osteoarthritis and an intact rotator cuff and in a subgroup of patients aged 60 years or younger. PATIENTS AND METHODS: Shoulder arthroplasties recorded in the National Joint Registry, UK, between April 1, 2012 and June 30, 2021, were linked to Hospital Episode Statistics in England. Elective TSAs and HAs were matched on propensity scores based on 11 variables. The primary outcome was all-cause revision. Secondary outcomes were combined revision/non-revision reoperations, 30-day inpatient complications, 1-year mortality, and length of stay. 95% confidence intervals (CI) were reported. RESULTS: 11,556 shoulder arthroplasties were included: 7,641 TSAs, 3,915 HAs. At 8 years 95% (CI 94-96) of TSAs and 91% (CI 90-92) of HAs remained unrevised. The hazard ratio (HR) varied across follow-up: 4-year HR 2.7 (CI 1.9-3.5), 8-year HR 2.0 (CI 0.5-3.5). Rotator cuff insufficiency was the most common revision indication. In patients aged 60 years or younger prosthesis survival at 8 years was 92% (CI 89-94) following TSA and 84% (CI 80-87) following HA. CONCLUSION: The risk of revision was higher following HA in patients with osteoarthritis and an intact rotator cuff. Patients aged 60 years and younger had a higher risk of revision following HA.