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BACKGROUND: Elbow stiffness is one of the most common complications after operative fixation of distal humerus fractures; however, there is relatively limited literature assessing which factors are associated with this problem. The purpose of this study is to identify risk factors associated with dysfunctional elbow stiffness in distal humerus fractures after operative fixation. METHODS: A retrospective review of all distal humerus fractures that underwent operative fixation (AO/OTA 13A-C) at a single level 1 trauma center from November 2014 to October 2021. A minimum six-month follow-up was required for inclusion or the outcome of interest. Dysfunctional elbow stiffness was defined as a flexion-extension arc of less than 100° at latest follow-up or any patient requiring surgical treatment for limited elbow range of motion. RESULTS: A total of 110 patients with distal humerus fractures were included in the study: 54 patients comprised the elbow stiffness group and 56 patients were in the control group. Average follow-up of 343 (59 to 2,079) days. Multiple logistic regression showed that orthogonal plate configuration (aOR: 5.70, 95% CI: 1.91-16.99, p=0.002), and longer operative time (aOR: 1.86, 95% CI: 1.11-3.10, p=0.017) were independently associated with an increased odds of elbow stiffness. OTA/AO 13A type fractures were significantly associated with a decreased odds of stiffness (aOR: 0.16, 95% CI: 0.03-0.80, p=0.026). Among 13C fractures, olecranon osteotomy (aOR: 5.48, 95% CI: 1.08-27.73, p=0.040) was also associated with an increased odds of elbow stiffness. There were no significant differences in injury mechanism, Gustilo-Anderson classification, reduction quality, days to surgery from admission, type of fixation, as well as rates of ipsilateral upper extremity fracture, neurovascular injury, nonunion, or infection between the two groups. CONCLUSION: Dysfunctional elbow stiffness was observed in 49.1% of patients who underwent operative fixation of distal humerus fractures in the present study. Orthogonal plate configuration, olecranon osteotomy, and longer operative time were associated with an increased odds of dysfunctional elbow stiffness; however, 13A type fractures were associated with decreased odds of stiffness. Patients with these injuries should be counseled on their risk of stiffness following surgery, and modifiable risk factors like plate positioning and performing an olecranon osteotomy should be considered by surgeons.
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BACKGROUND: Bacteriophage (phage) therapy is a promising alternative antimicrobial approach which has the potential to transform the way we treat bacterial infections. The antibiotic resistance crisis is driving renewed interest in phage therapy. There are currently no licenced phage therapy medicinal products and phage therapy is used in small but growing patient numbers on an unlicensed basis. OBJECTIVES: This article provides guidelines on the assessment of patient suitability for unlicensed phage therapy for clinicians in the United Kingdom. SOURCES: This article builds on Health Improvement Scotland's recommendation for the consideration of phage therapy in difficult-to-treat infection and the experience of the author group who have collectively assessed the suitability of 30 patients for phage therapy. CONTENT: In the UK, unlicensed medicines, including phages, may be considered to meet special clinical needs. The use of unlicensed medicines is governed by national legislation and local NHS Trust policies. Phages can be used in any NHS Trust and decisions about suitability should be made via existing local clinical management pathways. This article sets out guidelines to support local clinical teams in the assessment of patient suitability for phage therapy. Clinical and microbiological considerations are presented, including allergy and pregnancy.
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BACKGROUND: Taxane- based chemotherapy is widely used in patients with platinum- and immunotherapy refractory, metastatic urothelial carcinoma (mUC). Outcomes are poor and biomarkers associated with outcome are lacking. We aim to identify cancer hallmarks associated with survival in patients receiving paclitaxel. METHODS: Whole-transcriptome profiles were generated for a subset of patients enrolled in a randomised phase II study investigating paclitaxel and pazopanib in platinum refractory mUC (PLUTO, EudraCT 2011-001841-34). Estimates of gene expression were calculated and input into the Almac proprietary analysis pipeline and signature scores were calculated using ClaraT V3.0.0. Ten key gene signatures were assessed: Immuno-Oncology, Epithelial to Mesenchymal Transition, Angiogenesis, Proliferation, Cell Death, Genome Instability, Energetics, Inflammation, Immortality and Evading Growth. Hazard ratios were calculated using Cox regression model and Kaplan-Meier methods were used to estimate progression free survival (PFS) and overall survival (OS). RESULTS: 38 and 45 patients treated with paclitaxel or pazopanib were included. Patients with high genome instability expression treated with paclitaxel had significantly improved survival with a HR of 0.29 (95% CI: 0.14-0.61, p=0.001) and HR 0.34 (95% CI: 0.17-0.69, p=0.003) for PFS and OS, respectively. Similarly, patients with high evading growth suppressor expression treated with paclitaxel had improved PFS and OS with a HR of 0.35 (95% CI: 0.19-0.77, p=0.007) and HR 0.46 (95% CI: 0.23-0.91, p=0.026), respectively. No other gene signatures had significant impact on outcome. In both paclitaxel and pazopanib cohorts, angiogenesis activation was associated with worse PFS and OS, and VEGF targeted therapy did not improve outcomes. CONCLUSION: High Genome-instability and Evading-growth suppressor biologies are associated with improved survival in patients with platinum refractory mUC receiving paclitaxel. These may refine mUC risk stratification and guide treatment decision in the future.
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The landscape of the management of renal cell carcinoma has evolved substantially in the last decade, leading to improved survival in localised and advanced disease. We review the epidemiology, pathology, and diagnosis of renal cell carcinoma and discuss the evidence for current management strategies from localised to metastatic disease. Developments in adjuvant therapies are discussed, including use of pembrolizumab-the first therapy to achieve overall survival benefit in the adjuvant setting. The treatment of advanced disease, including landmark trials that have established immune checkpoint inhibition as a standard of care, are also reviewed. We also discuss the current controversies that exist surrounding the management of metastatic renal cell carcinoma, including the use of risk assessment models for disease stratification and treatment selection for frontline therapy. Management of non-clear cell renal cell carcinoma subtypes is also reviewed. Future directions of research, including a discussion of ongoing clinical trials and the need for reliable biomarkers to guide treatment in kidney cancer, are also highlighted.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/terapia , Carcinoma de Células Renales/epidemiología , Neoplasias Renales/terapia , Neoplasias Renales/patología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Quimioterapia AdyuvanteRESUMEN
Endometrial cancer (EC) is a devastating and common disease affecting women's health. The NCI Surveillance, Epidemiology, and End Results Program predicted that there would be >66,000 new cases in the United States and >13,000 deaths from EC in 2023, and EC is the sixth most common cancer among women worldwide. Regulation of mitochondrial metabolism plays a role in tumorigenesis. In proliferating cancer cells, mitochondria provide the necessary building blocks for biosynthesis of amino acids, lipids, nucleotides, and glucose. One mechanism causing altered mitochondrial activity is mitochondrial DNA (mtDNA) mutation. The polyploid human mtDNA genome is a circular double-stranded molecule essential to vertebrate life that harbors genes critical for oxidative phosphorylation plus mitochondrial-derived peptide genes. Cancer cells display aerobic glycolysis, known as the Warburg effect, which arises from the needs of fast-dividing cells and is characterized by increased glucose uptake and conversion of glucose to lactate. Solid tumors often contain at least one mtDNA substitution. Furthermore, it is common for cancer cells to harbor mixtures of wild-type and mutant mtDNA genotypes, known as heteroplasmy. Considering the increase in cancer cell energy demand, the presence of functionally relevant carcinogenesis-inducing or environment-adapting mtDNA mutations in cancer seems plausible. We review 279 EC tumor-specific mtDNA single nucleotide variants from 111 individuals from different studies. Many transition mutations indicative of error-prone DNA polymerase γ replication and C to U deamination events were present. We examine the spectrum of mutations and their heteroplasmy and discuss the potential biological impact of recurrent, non-synonymous, insertion, and deletion mutations. Lastly, we explore current EC treatments, exploiting cancer cell mitochondria for therapy and the prospect of using mtDNA variants as an EC biomarker.
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Antibody-drug conjugates have transformed treatment for urothelial cancer (UC). Enfortumab vedotin is the new standard of care in the first-line setting for advanced UC. A personalised approach targeting HER2 in UC is currently being explored.
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Anticuerpos Monoclonales , Carcinoma de Células Transicionales , Moléculas de Adhesión Celular , Receptor ErbB-2 , Humanos , Receptor ErbB-2/metabolismo , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Anticuerpos Monoclonales/uso terapéutico , Moléculas de Adhesión Celular/metabolismo , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/patología , Inmunoconjugados/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , NectinasRESUMEN
Upper tract urothelial carcinoma (UTUC) is an aggressive and difficult malignancy to treat. Owing to its rarity and the lack of specific high-level data, management mirrors that of urothelial cancer of the bladder (UCB). Over the past decade, UTUC has shown minimal improvement in survival rates. Its location makes the diagnosis and staging of UTUC more complex. Moreover, surgery often leads to a decline in renal function, rendering a proportion of patients ineligible for cisplatin. There is debate as to how best manage locally advanced UTUC perioperatively. Although immune checkpoint inhibitors (ICIs) have changed the treatment landscape for UCB, the response to ICIs in UTUC has been variable. With new technologies, our understanding of the molecular biology of UTUC has grown, helping to identify key molecular differences from UCB. This review summarises the evidence available on UTUC as a disease entity, discusses treatment in perioperative and metastatic settings, and considers future directions for the management of patients diagnosed with UTUC.
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BACKGROUND: Molecular syndromic panels can improve rapidity of results and ease clinical laboratory workflow, although caution has been raised for potential false-positive results. Upon implementation of a new panel for infectious diarrhea (BioFire® FilmArray® Gastrointestinal [GI] Panel, bioMérieux) in our clinical laboratory, a higher than expected number of stool samples with norovirus were detected. OBJECTIVES: The goal of this study was to investigate positive percent agreement and the false-positive rate of norovirus detected by the multiplex BioFire GI panel compared to a singleplex commercial assay. STUDY DESIGN: From October 2023 to January 2024, all prospective stool samples with a positive norovirus result by BioFire had melting curves reviewed manually using the BioFire FilmArray Torch System. Stool samples further underwent testing by a supplementary real-time RT-PCR assay (Xpert® Norovirus, Cepheid) for comparative analysis. RESULTS: Of the 50 stool samples with norovirus detected by BioFire, 18 (36 %) tested negative by Xpert (deemed "false-positives"). Furthermore, melting curve analysis revealed nearly all of these samples had atypical melting curve morphologies for the "Noro-1" target on BioFire (16/18, 89 %), which was statistically significant (Odds Ratio 173.2, 95 % CI [22.2, 5326.9], p < 0.0001). Stool samples with multiple pathogens detected by BioFire including norovirus were not more likely to produce false-positive norovirus results (Odds Ratio 1, 95 % CI [0.3, 3.3], p = 1). CONCLUSIONS: Although not described in the manufacturer's Instructions for Use, we propose routine manual review of melting curves for the BioFire GI panel prior to reporting, to mitigate potential false-positive norovirus results.
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Infecciones por Caliciviridae , Heces , Gastroenteritis , Norovirus , Norovirus/aislamiento & purificación , Norovirus/genética , Humanos , Infecciones por Caliciviridae/diagnóstico , Infecciones por Caliciviridae/virología , Reacciones Falso Positivas , Heces/virología , Estudios Prospectivos , Gastroenteritis/virología , Gastroenteritis/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Temperatura de Transición , Adulto , Masculino , Femenino , Diarrea/virología , Diarrea/diagnóstico , Persona de Mediana Edad , Preescolar , Niño , Anciano , Adolescente , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Sensibilidad y Especificidad , LactanteRESUMEN
Recent years have seen increased attention given to identifying and describing the levels of gambling participation that confer a risk of harm in order to generate public health advice regarding lower-risk gambling. However, most of the existing literature has failed to explicitly assess these limits in a prospective manner. The purpose of this study is to employ a methodology consistent with prior investigations to evaluate the level of gambling participation associated with an increased risk of future gambling-related harm. Using data from the Alberta Gambling Research Institute's National Project Online Panel Survey, risk ratios and Receiver Operating Characteristic (ROC) analyses were used to determine the relative risk of gambling-related harm associated with participating in a greater number of gambling formats, gambling more days per month, and spending a greater proportion of income gambling. Prospective lower-risk limits were largely consistent with those identified in previous cross-sectional analyses (e.g., no more than two gambling formats, no more than once a week), with the exception that higher limits were found for the percent of household income spent gambling (3.4-6.4% vs. 1%). We advise that future research on lower-risk gambling limits consider the use of more granular assessment instruments and prospective methods to more closely evaluate the association between gambling participation and gambling harm.
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Management of metastatic bladder cancer has historically been challenging. However, enfortumab vedotin plus pembrolizumab (EV/P) has recently been accepted as a new standard of care, replacing platinum-based chemotherapy, because of improvements in survival and response rates. The benefits of the EV/P combination and some of the questions that arise in this new treatment landscape are discussed.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Metástasis de la Neoplasia , Predicción , Antineoplásicos Inmunológicos/uso terapéuticoRESUMEN
BACKGROUND: Reliable biomarkers in renal cell carcinoma (RCC) remain elusive. While several markers have been shown to be associated with prognosis, and may aid in risk assessment, predictive biomarkers of response to immune checkpoint inhibitors (ICIs) have not been established. Previous studies have shown that a high pretreatment neutrophil-lymphocyte ratio (NLR) is a negative prognostic factor in RCC. However, a clinically useful cut-off for the predictive and prognostic value of NLR has not been well defined. METHODS: We conducted a retrospective analysis of 132 patients with previously untreated metastatic clear cell RCC (ccRCC) who received first line ICI-based therapy. ICI-based therapy included anti-PD-1/PD-L1 alone or in combination with anti-CTLA-4 or VEGF-TKI. Platelet, haemoglobin, neutrophil and lymphocyte counts were collected prior to treatment and at 12-weeks after treatment initiation. Radiologic response at 12-weeks and overall survival (OS) data was also collected. RESULTS: Low haemoglobin, high platelet count, and NLR ≥3 were statistically significant negative predictive biomarkers when assessed at 12-weeks, but not at baseline. Median OS was shorter in patients with low haemoglobin (20.3 months vs. 51.6 months, P = .009), high platelet count (14.3 months vs. 43.8 months, P = .003), and NLR ≥ 3 (17.5 months vs. 40.3 months, P < .001) at 12-weeks. In an IMDC-risk adjusted analysis, only NLR ≥3 at 12-weeks remained statistically significant (OR of 2.11, P = .003) A dynamic change towards lower absolute NLR overtime was associated with longer OS. In patients who had baseline NLR ≥ 3, those who achieved NLR < 3 at 12-weeks demonstrated significant longer median OS compared to those whose NLR remained persistently ≥ 3 (40.3 months vs. 14.7 months, P = .004). CONCLUSION: NLR ≥3, low haemoglobin and elevated platelet count after 12-weeks of ICI-based first line therapy were negatively prognostic and predictive in patients with metastatic RCC. Normalization of NLR in patients with baseline elevation was associated with longer median OS and response to therapy. These results suggest that monitoring of routine haematologic biomarkers during therapy may provide important predictive and prognostic information, beyond what is available with baseline risk assessment scoring systems.
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Carcinoma de Células Renales , Hemoglobinas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Renales , Neutrófilos , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/sangre , Carcinoma de Células Renales/secundario , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/sangre , Neoplasias Renales/patología , Recuento de Plaquetas , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Pronóstico , Anciano , Hemoglobinas/análisis , Linfocitos , Biomarcadores de Tumor/sangre , Recuento de Linfocitos , Adulto , Anciano de 80 o más AñosRESUMEN
Listeriosis has more than a 50% mortality when the central nervous system is involved, necessitating rapid diagnosis and treatment. We present four patients with brain abscesses in the setting of diagnosed neurolisteriosis, all of which demonstrated an odd presentation of multiple small, contiguous tubular lesions with rim enhancement on magnetic resonance imaging. Our review of published cases of neurolisteriosis suggests that this may be a useful pattern to identify neurolisteriosis abscesses, allowing earlier detection and therapy.
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Background: Ankle sprains are a common musculoskeletal injury among the general population and often involve the lateral ligament complex. Although the majority of ankle sprains are treated successfully with nonsurgical conservative measures, an estimated 5% to 20% of ankle injuries ultimately develop chronic lateral ankle instability (CAI). Multiple surgical treatment modalities for the lateral ankle complex exist, such as anatomical and nonanatomical reconstruction. The current gold standard for primary surgical repair is the Broström-Gould procedure. This is the first article to provide PROMIS scores following BG and the largest study with 5-year outcomes for an open BG. Methods: This was a descriptive study of a retrospective cohort of patients undergoing a BG with a minimum follow-up of 5 years. Patient-reported outcome instruments collected postoperatively were PROMIS Pain, Physical Function, Depression, and FAAM. Further preoperative clinic characteristics were analyzed to correlate with the final outcome. The electronic medical record was queried for Current Procedural Terminology (CPT) code 27698 (Broström-Gould) from January 2010 to June 2017. Surveys were conducted in the clinic and through phone interviews. Patient charts were reviewed to obtain basic patient demographic information including sex, age, race, and body mass index (BMI). The following preoperative variables were recorded: history of prior CAI procedures, history of major trauma, duration of symptoms, number of diagnosed ankle sprains, other collagen pathologies, generalized ligament laxity, participation in sports/activity level, peroneal subluxation, clinically diagnosed peroneus longus or brevis tendinopathy, deltoid ligament injury, anterior ankle impingement, and posterior ankle impingement. The PROMIS and Foot and Ankle Ability Measure (FAAM) scores were obtained with a combination of clinic and phone interviews. Data were aggregated in Microsoft Excel and entered in R (version 4.2.0) for statistical analysis. Results: Our results show that the minimum 5-year patient-reported PROMIS scores for patients following a Broström-Gould procedure are as follows: PROMIS physical function, 50.5; PROMIS pain interference, 48.2; and PROMIS depression, 38.2. This indicates, at a minimum, that patients 5 years removed from the procedure are within 1 SD of the general population in regard to PROMIS physical function and pain. Our patient-reported FAAM, activities of daily living, and FAAM sports scores were 59.6 and 13.0 respectively. Preoperative magnetic resonance imaging (MRI) findings were recorded. Arthroscopic examination was performed before lateral ligaments reconstruction for patients with intra-articular pathologies confirmed on MRI. Conclusion: The findings from our study offer evidence supporting the effectiveness of the Broström-Gould procedure to be associated with normal physical function, even 5 years after surgery. Furthermore, our research identified specific factors such as tobacco use, diabetes, and sports participation that independently correlated with reported outcome measures. These insights enable physicians to better manage patient expectations and tailor treatment strategies accordingly. Our study establishes a foundation for future prospective research endeavors that aim to leverage the PROMIS system for comprehensive outcome assessments. Level of Evidence: Level III, retrospective cohort study.
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BACKGROUND: Whether Inuit in Canada experience disparities in lung cancer survival remains unknown. When requiring investigation and treatment for lung cancer, all residents of Nunavik, the Inuit homeland in Quebec, are sent to the McGill University Health Centre (MUHC), in Montréal. We sought to compare survival among patients with lung cancer at the MUHC, who were residents of Nunavik and Montréal, Quebec, respectively. METHODS: We conducted a retrospective cohort study. Using lung cancer registry data, we identified Nunavik residents with histologically confirmed lung cancer diagnosed between 2005 and 2017. We aimed to match 2 Montréal residents to each Nunavik resident on sex, age, calendar year of diagnosis, and histology (non-small cell lung cancer v. small cell lung cancer). We reviewed medical records for data on additional patient characteristics and treatment, and obtained vital status from a provincial registry. We compared survival using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: We included 95 residents of Nunavik and 185 residents of Montréal. For non-small cell lung cancer, median survival times were 321 (95% confidence interval [CI] 184-626) days for Nunavik (n = 71) and 720 (95% CI 536-1208) days for Montréal residents (n = 141). For small cell lung cancer, median survival times were 190 (95% CI 159-308) days for Nunavik (n = 24) and 270 (95% CI 194-766) days for Montréal residents (n = 44). Adjusting for matching variables, stage, performance status, and comorbidity, Nunavik residents had a higher hazard of death (hazard ratio 1.68, 95% CI 1.17-2.41). INTERPRETATION: Nunavik residents experience disparities in survival after lung cancer diagnosis. Although studies in other Inuit Nunangat regions are needed, our findings point to an urgent need to ensure that interventions aimed at improving lung cancer survival, including lung cancer screening, are accessible to Inuit Nunangat residents.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Estudios Retrospectivos , Neoplasias Pulmonares/epidemiología , Carcinoma Pulmonar de Células Pequeñas/terapia , Detección Precoz del Cáncer , Estudios de Cohortes , Quebec/epidemiologíaRESUMEN
Introduction. BK polyomavirus (BKPyV) quantitative testing is an important screening tool post-transplantation, although interpretation can be challenging due to lack of standardization, assay heterogeneity and variability of BKPyV DNA over time (in urine).Methods. Remnant clinical EDTA plasma and urine samples were tested by the cobas BKV test and a validated laboratory-developed test (LDT). Accuracy [positive and negative percent agreement (PPA and NPA), Pearson's correlation, Bland-Altman analysis] and reproducibility were evaluated. To assess BKPyV DNA stability in urine, prospective urine samples were maintained at two different storage temperatures and tested in triplicate over 7 days.Results. Overall PPA was 95.6 % (43/45) and NPA was 94.4 % (170/180). For plasma, Pearson's correlation (0.950) and Bland-Altman analysis (0.113±0.22 log10 IU ml-1) showed high agreement. For neat urine, Pearson's correlation (0.842) and Bland-Altman analysis (0.326±0.80 log10 IU ml-1) showed somewhat higher variability. Reproducibility was high for the cobas BKV versus the LDT. BKPyV DNA levels in neat urine remained relatively stable over 7 days at both storage temperatures, although outlier results were intermittently detected.Conclusion. The cobas BKV test showed high agreement and reproducibility compared to the reference LDT. BKPyV viral load testing in urine has known limitations, but neat urine can be processed by the cobas BKV.
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Virus BK , Ácidos Nucleicos , Estudios Prospectivos , Reproducibilidad de los Resultados , ADNRESUMEN
BACKGROUND: As normal cells transform into cancers, their cell state changes, which may drive cancer cells into a stem-like or more primordial, foetal, or embryonic cell state. The transcriptomic profile of this final state may encode information about cancer's origin and how cancers relate to their normal cell counterparts. METHODS: Here, we used single-cell atlases to study cancer transformation in transcriptional terms. We utilised bulk transcriptomes across a wide spectrum of adult and childhood cancers, using a previously established method to interrogate their relationship to normal cell states. We extend and validate these findings using single-cell cancer transcriptomes and organ-specific atlases of colorectal and liver cancer. RESULTS: Our bulk transcriptomic data reveals that adult cancers rarely return to an embryonic state, but that a foetal state is a near-universal feature of childhood cancers. This finding was confirmed with single-cell cancer transcriptomes. CONCLUSIONS: Our findings provide a nuanced picture of transformation in human cancer, indicating cancer-specific rather than universal patterns of transformation pervade adult epithelial cancers.
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Neoplasias Hepáticas , Adulto , Humanos , Neoplasias Hepáticas/genética , Desarrollo Embrionario , Feto , Perfilación de la Expresión Génica , TranscriptomaRESUMEN
BACKGROUND: Low-Risk Alcohol Drinking Guidelines (LRDGs) aim to reduce the harms caused by alcohol. However, considerable discrepancies exist in the 'low-risk' thresholds employed by different countries. ARGUMENT/ANALYSIS: Drawing upon Canada's LRDGs update process, the current paper offers the following propositions for debate regarding the establishment of 'low-risk' thresholds in national guidelines: (1) as an indicator of health loss, years of life lost (YLL) has several advantages that could make it more suitable for setting guidelines than deaths, premature deaths or disability adjusted years of life (DALYs) lost. (2) Presenting age-specific guidelines may not be the most appropriate way of providing LRDGs. (3) Given past overemphasis on the so-called protective effects of alcohol on health, presenting cause-specific guidelines may not be appropriate compared with a 'whole health' effect derived from a weighted composite risk function comprising conditions that are causally related to alcohol consumption. (4) To help people reduce their alcohol use, presenting different risk zones associated with alcohol consumption instead of a single low risk threshold may be advantageous. CONCLUSIONS: National LRDGs should be based on years of life lost and should be neither age-specific nor cause-specific. We recommend using risk zones rather than a single drinking threshold to help people assess their own risk and encourage the adoption of behaviours with positive health impacts across the alcohol use spectrum.
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Consumo de Bebidas Alcohólicas , Personas con Discapacidad , Humanos , Riesgo , Mortalidad Prematura , Recolección de DatosRESUMEN
BACKGROUND: Mechanobiology can help optimize spinal fusion by providing insights into the mechanical environment required for bone healing and fusion. This includes understanding the optimal loading conditions, the mechanical properties of implanted materials, and the effects of mechanical stimuli on the cells involved in bone formation. The present article reviews the evidence for surface technologies and implant modification of spinal cages in enhancing spinal fusion. METHODS: Databases used included Embase, MEDLINE, Springer, and Cochrane Library. Relevant articles were identified using specific keywords and search fields. Only systematic reviews, meta-analyses, review articles, and original research articles in English were included. Two researchers independently performed the search and selection process. A flowchart of the search strategy and study selection method is provided in the article. RESULTS: The studies indicate that surface modification can significantly enhance osseointegration and interbody fusion by promoting cellular adhesion, proliferation, differentiation, and mineralization. Various surface modification techniques such as coating, etching, nanotopography, and functionalization achieve this. Similarly, implant material modification can improve implant stability, biocompatibility, and bioactivity, leading to better fusion outcomes. Mechanobiology plays a vital role in this process by influencing the cellular response to mechanical cues and promoting bone formation. CONCLUSIONS: The studies reviewed indicate that surface technologies and implant material modification are promising approaches for improving the success of spinal cage fusion. Mechanobiology is critical in this process by influencing the cellular response to mechanical signals and promoting bone growth.