The clinical effectiveness and cost-effectiveness of ablative therapies in the management of liver metastases: systematic review and economic evaluation

Background: Many deaths from cancer are caused by metastatic burden. Prognosis and survival rates vary, but survival beyond 5 years of patients with untreated metastatic disease in the liver is rare. Treatment for liver metastases has largely been surgical resection, but this is feasible in only approximately 20–30% of people. Non-surgical alternatives to treat some liver metastases can include various forms of ablative therapies and other targeted treatments.Objectives: To evaluate the clinical effectiveness and cost-effectiveness of the different ablative and minimally invasive therapies for treating liver metastases.Data sources: Electronic databases including MEDLINE, EMBASE and The Cochrane Library were searched from 1990 to September 2011. Experts were consulted and bibliographies checked.Review methods: Systematic reviews of the literature were undertaken to appraise the clinical effectiveness and cost-effectiveness of ablative therapies and minimally invasive therapies used for people with liver metastases. Studies were any prospective study with sample size greater than 100 participants. A probabilistic model was developed for the economic evaluation of the technologies where data permitted.Results: The evidence assessing the clinical effectiveness and cost-effectiveness of ablative and other minimally invasive therapies was limited. Nine studies of ablative therapies were included in the review; each had methodological shortcomings and few had a comparator group. One randomised controlled trial (RCT) of microwave ablation versus surgical resection was identified and showed no improvement in outcomes compared with resection. In two prospective case series studies that investigated the use of laser ablation, mean survival ranged from 41 to 58 months. One cohort study compared radiofrequency ablation with surgical resection and five case series studies also investigated the use of radiofrequency ablation. Across these studies the median survival ranged from 44 to 52 months. Seven studies of minimally invasive therapies were included in the review. Two RCTs compared chemoembolisation with chemotherapy only. Overall survival was not compared between groups and methodological shortcomings mean that conclusions are difficult to make. Two case series studies of laser ablation following chemoembolisation were also included; however, these provide little evidence of the use of these technologies in combination. Three RCTs of radioembolisation were included. Significant improvements in tumour response and time to disease progression were demonstrated; however, benefits in terms of survival were equivocal. An exploratory survival model was developed using data from the review of clinical effectiveness. The model includes separate analyses of microwave ablation compared with surgery and radiofrequency ablation compared with surgery and one of radioembolisation in conjunction with hepatic artery chemotherapy compared with hepatic artery chemotherapy alone. Microwave ablation was associated with an incremental cost-effectiveness ratio (ICER) of £3664 per quality-adjusted life-year (QALY) gained, with microwave ablation being associated with reduced cost but also with poorer outcome than surgery. Radiofrequency ablation compared with surgical resection for solitary metastases < 3 cm was associated with an ICER of –£266,767 per QALY gained, indicating that radiofrequency ablation dominates surgical resection. Radiofrequency ablation compared with surgical resection for solitary metastases ? 3 cm resulted in poorer outcomes at lower costs and a resultant ICER of £2538 per QALY gained. Radioembolisation plus hepatic artery chemotherapy compared with hepatic artery chemotherapy was associated with an ICER of £37,303 per QALY gained.Conclusions: There is currently limited high-quality research evidence upon which to base any firm decisions regarding ablative therapies for liver metastases. Further trials should compare ablative therapies with surgery, in particular. A RCT would provide the most appropriate design for undertaking any further evaluation and should include a full economic evaluation, but the group to be randomised needs careful selection.Source of funding: Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research

Tree phyllospheres are a habitat for diverse populations of CO-oxidizing bacteria

Carbon monoxide (CO) is both a ubiquitous atmospheric trace gas and an air pollutant. While aerobic CO-degrading microorganisms in soils and oceans are estimated to remove ~370 Tg of CO per year, the presence of CO-degrading microorganisms in above-ground habitats, such as the phyllosphere, and their potential role in CO cycling remains unknown. CO-degradation by leaf washes of two common British trees, Ilex aquifolium and Crataegus monogyna, demonstrated CO uptake in all samples investigated. Based on the analyses of taxonomic and functional genes, diverse communities of candidate CO-oxidizing taxa were identified, including members of Rhizobiales and Burkholderiales which were abundant in the phyllosphere at the time of sampling. Based on predicted genomes of phyllosphere community members, an estimated 21% of phyllosphere bacteria contained CoxL, the large subunit of CO-dehydrogenase. In support of this, data mining of publicly available phyllosphere metagenomes for genes encoding CO-dehydrogenase subunits demonstrated that, on average, 25% of phyllosphere bacteria contained CO-dehydrogenase gene homologues. A CO-oxidizing Phyllobacteriaceae strain was also isolated from phyllosphere samples which contains genes encoding both CO-dehydrogenase as well as a ribulose-1,5-bisphosphate carboxylase-oxygenase. These results suggest that the phyllosphere supports diverse and potentially abundant CO-oxidizing bacteria, which are a potential sink for atmospheric CO

Contrasting Responses of Rhizosphere Bacterial, Fungal, Protist and Nematode Communities to Nitrogen Fertilisation and Crop Genotype in Field Grown Oilseed Rape (Brassica napus)

© 2021 Picot, Hale, Hilton, Teakle, Schäfer, Huang, Perryman, West and Bending. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/The rhizosphere microbiome is considered to play a key role in determining crop health. However, current understanding of the factors which shape assembly and composition of the microbiome is heavily biased toward bacterial communities, and the relevance for other microbial groups is unclear. Furthermore, community assembly is determined by a variety of factors, including host genotype, environment and agricultural management practices, and their relative importance and interactions remain to be elucidated. We investigated the impact of nitrogen fertilization on rhizosphere bacterial, fungal, nematode and protist communities of 10 contrasting oilseed rape genotypes in a field experiment. We found significant differences in the composition of bacteria, fungi, protist and nematode communities between the rhizosphere and bulk soil. Nitrogen application had a significant but weak effect on fungal, bacterial, and protist community composition, and this was associated with increased relative abundance of a complex of fungal pathogens in the rhizosphere and soil, including Mycosphaerella sp. and Leptosphaeria sp. Network analysis showed that nitrogen application had different effects on microbial community connectivity in the soil and rhizosphere. Crop genotype significantly affected fungal community composition, with evidence for a degree of genotype specificity for a number of pathogens, including L. maculans, Alternaria sp., Pyrenopeziza brassicae, Olpidium brassicae, and L. biglobosa, and also potentially beneficial Heliotales root endophytes. Crop genotype had no significant effect on assembly of bacteria, protist or nematode communities. There was no relationship between genetic distance of crop genotypes and the extent of dissimilarity of rhizosphere microbial communities. Field disease assessment confirmed infection of crops by Leptosphaeria sp., P. brassicae, and Alternaria sp., indicating that rhizosphere microbiome sequencing was an effective indicator of plant health. We conclude that under field conditions soil and rhizosphere nutrient stoichiometry and crop genotype are key factors determining crop health by influencing the infection of roots by pathogenic and mutualistic fungal communities, and the connectivity and stability of rhizosphere microbiome interaction networks.Peer reviewedFinal Published versio

Circadian rhythms in the plant host influence rhythmicity of rhizosphere microbiota

Background Recent studies demonstrated that microbiota inhabiting the plant rhizosphere exhibit diel changes in abundance. To investigate the impact of plant circadian rhythms on bacterial and fungal rhythms in the rhizosphere, we analysed temporal changes in fungal and bacterial communities in the rhizosphere of Arabidopsis plants overexpressing or lacking function of the circadian clock gene LATE ELONGATED HYPOCOTYL (LHY). Results Under diel light–dark cycles, the knock-out mutant lhy-11 and the gain-of-function mutant lhy-ox both exhibited gene expression rhythms with altered timing and amplitude compared to wild-type plants. Distinct sets of bacteria and fungi were found to display rhythmic changes in abundance in the rhizosphere of both of these mutants, suggesting that abnormal patterns of rhythmicity in the plant host caused temporal reprogramming of the rhizosphere microbiome. This was associated with changes in microbial community structure, including changes in the abundance of fungal guilds known to impact on plant health. Under constant environmental conditions, microbial rhythmicity persisted in the rhizosphere of wild-type plants, indicating control by a circadian oscillator. In contrast, loss of rhythmicity in lhy-ox plants was associated with disrupted rhythms for the majority of rhizosphere microbiota. Conclusions These results show that aberrant function of the plant circadian clock is associated with altered rhythmicity of rhizosphere bacteria and fungi. In the long term, this leads to changes in composition of the rhizosphere microbiome, with potential consequences for plant health. Further research will be required to understand the functional implications of these changes and how they impact on plant health and productivity

Comparative genomics across three ensifer species using a new complete genome sequence of the Medicago symbiont Sinorhizobium (Ensifer) meliloti WSM1022

Here, we report an improved and complete genome sequence of Sinorhizobium (Ensifer) meliloti strain WSM1022, a microsymbiont of Medicago species, revealing its tripartite structure. This improved genome sequence was generated combining Illumina and Oxford nanopore sequencing technologies to better understand the symbiotic properties of the bacterium. The 6.75 Mb WSM1022 genome consists of three scaffolds, corresponding to a chromosome (3.70 Mb) and the pSymA (1.38 Mb) and pSymB (1.66 Mb) megaplasmids. The assembly has an average GC content of 62.2% and a mean coverage of 77X. Genome annotation of WSM1022 predicted 6058 protein coding sequences (CDSs), 202 pseudogenes, 9 rRNAs (3 each of 5S, 16S, and 23S), 55 tRNAs, and 4 ncRNAs. We compared the genome of WSM1022 to two other rhizobial strains, closely related Sinorhizobium (Ensifer) meliloti Sm1021 and Sinorhizobium (Ensifer) medicae WSM419. Both WSM1022 and WSM419 species are high-efficiency rhizobial strains when in symbiosis with Medicago truncatula, whereas Sm1021 is ineffective. Our findings report significant genomic differences across the three strains with some similarities between the meliloti strains and some others between the high efficiency strains WSM1022 and WSM419. The addition of this high-quality rhizobial genome sequence in conjunction with comparative analyses will help to unravel the features that make a rhizobial symbiont highly efficient for nitrogen fixation

Plant circadian clock control of Medicago truncatula nodulation via regulation of Nodule Cysteine-Rich peptides

Legumes house nitrogen-fixing endosymbiotic rhizobia in specialized polyploid cells within root nodules, which undergo tightly regulated metabolic activity. By carrying out expression analysis of transcripts over time in Medicago truncatula nodules we found that the circadian clock enables coordinated control of metabolic and regulatory processes linked to nitrogen fixation. This involves the circadian clock-associated transcriptional factor LATE ELONGATED HYPOCOTYL (LHY), with lhy mutants being affected in nodulation. Rhythmic transcripts in root nodules include a subset of Nodule-specific Cysteine Rich peptides (NCRs) that have the LHY-bound conserved Evening Element in their promoters. Until now, studies have suggested that NCRs act to regulate bacteroid differentiation and keep the rhizobial population in check. However, these conclusions came from the study of a few members of this very large gene family that has complex diversified spatio-temporal expression. We suggest that rhythmic expression of NCRs may be important for temporal coordination of bacterial activity with the rhythms of the plant host, in order to ensure optimal symbiosis

Omalizumab for previously treated chronic spontaneous urticaria

Urticaria (also known as hives, welts or nettle rash) is a vascular reactioncharacterised by the transient appearance of raised, itchy lesions ('wheals')on the skin. It occurs when histamine and other chemicals are released from under the surface of the skin, causing tissues to swell. The lifetime prevalence of chronic urticaria in the UK is 0.5 1%, but approximately 15% of people experience urticaria at some time in their lives. For many people with urticaria, the cause of their condition is unknown. Individual wheals can change size rapidly and move around the skin, disappearing in one place and then reappearing somewhere else on the body. They generally appear on the skin for no longer than 24 hours; however, the condition may persist for several months. Angioedema (swelling of lips, hands and feet) may also be present. When symptoms are present for more than 6 weeks, the condition is considered to be chronic. Symptoms may persist for 3 5 years in approximately 50% of people, and for more than 10 years in 20% of people. Initial treatment of chronic spontaneous urticaria is a non-sedating H1- antihistamine (for example, cetirizine, levocetirizine, fexofenadine, loratadine, bilastine, desloratadine). Dose escalation of the antihistamine (2-fold and then 4-fold) may be required if the standard dose is ineffective. Subsequent treatment options for people whose condition does not respond to non- sedating antihistamines include leukotriene receptor antagonists, H2-receptor antagonists, immunosuppressant drugs (such as ciclosporin, mycophenolate mofetil and methotrexate) and tetrahydrofolate dehydrogenase inhibitors (such as dapsone). Oral corticosteroid pulses may be used to treat exacerbations

Cirugía Para La Obesidad

Antecedentes: Se considera la cirugía bariátrica (para la disminución del peso) como un tratamiento de la obesidad cuando han fracasado otros tratamientos. Los efectos de los procedimientos bariátricos disponibles son inciertos comparados con el tratamiento médico y entre ellos. Ésta es una actualización de la revisión sistemática Cochrane publicada por primera vez en 2003 y actualizada en 2005. Objetivo: Evaluar los efectos de la cirugía bariátrica para la obesidad. Estratégia de búsqueda: Los estudios se identificaron en búsquedas electrónicas en múltiples bases de datos bibliográficas, complementadas con búsquedas en listas de referencias y con la consulta con expertos en la investigación sobre la obesidad. Criterios de selección: Ensayos controlados aleatorios (ECA) que compararon diferentes procedimientos quirúrgicos, y ensayos controlados aleatorios (ECA), ensayos clínicos controlados y estudios de cohortes prospectivos que compararon la cirugía con el tratamiento no quirúrgico de la obesidad. Obtención y análisis de datos: Los datos fueron extraídos por un revisor y verificados independientemente por dos revisores. Dos revisores de forma independiente evaluaron la calidad de los ensayos. Resultados principales: Se incluyeron 26 estudios. Tres ensayos controlados aleatorios y tres estudios de cohortes prospectivos compararon la cirugía con el tratamiento no quirúrgico, y 20 ensayos controlados aleatorios compararon diferentes procedimientos bariátricos. El riesgo de sesgo de muchos ensayos fue incierto; y sólo cinco tuvieron una adecuada ocultación de la asignación. No era apropiado un metanálisis. El tratamiento quirúrgico dio como resultado una mayor pérdida de peso que el tratamiento convencional en la obesidad moderada (índice de masa corporal mayor de 30), así como en la grave. Hubo también disminución de las comorbilidades, como la diabetes y la hipertensión. Después de dos años mejoró la calidad de vida relacionada con la salud, pero los efectos a los diez años están menos claros. El tratamiento quirúrgico se asocia con complicaciones, como la embolia pulmonar, y ocurrieron algunas muertes posoperatorias. Se evaluaron cinco procedimientos bariátricos diferentes, pero algunas comparaciones fueron evaluadas sólo en un ensayo. Las limitadas pruebas indican que la pérdida de peso después de la derivación gástrica es mayor que con la gastroplastia en banda vertical o con la banda gástrica regulable, pero similar a la gastrectomía en manga aislada y a la derivación gástrica en banda. La gastrectomía en manga aislada parece que produce mayor pérdida de peso que la banda gástrica regulable. Las pruebas que comparan la gastroplastia en banda vertical con la banda gástrica regulable no son concluyentes. Los datos sobre la seguridad comparativa de los procedimientos bariátricos fueron limitados. La pérdida de peso y la calidad de vida fueron similares entre la cirugía abierta y los procedimientos laparoscópicos. Puede ocurrir que la cirugía laparoscópica termine como una intervención quirúrgica abierta. Conclusiones de los autores: El tratamiento quirúrgico es más efectivo que el tratamiento convencional. Ciertos procedimientos producen mayor pérdida de peso, pero los datos son limitados. Las pruebas sobre la seguridad son aún menos claras. Deben ser interpretados con cuidado la seguridad y la efectividad comparativas, debido a las limitaciones de las pruebas y a la deficiente calidad de los ensayos

Daratumumab in combination with bortezomib and dexamethasone for treating relapsed or refractory multiple myeloma (review of TA573): a single technology appraisal

In this report we provide a critique of the CDF review company’s submission (CS) to NICE for the review of TA5731 on the clinical effectiveness and cost effectiveness of daratumumab with bortezomib and dexamethasone (DBd) for treating relapsed or refractory multiple myeloma following the period of managed access within the Cancer Drugs Fund (CDF)

Oral metastasis of pulmonary adenocarcinoma: diagnosis and treatment

Introduction: Oral metastases are rare and represent 1% oro-facial neoplasms. The lung is the most common primary site for oral metastatic tumors. The diagnosis is based on histological analysis. Oral metastases have been associated with poor prognosis and is no longer a proven treatment. It was found in a 58-year old man diagnosed with lung cancer with a voluminous mandibular tumefaction following dental avulsion. The panoramic X-ray showed an area of ​​osteolysis compared to the extraction site. The histological and immunohistochemistry of the lesion showed a positivity of the marker CK7 and a negativity of TTF1, in favor of a lung origin. The biomolecular analysis revealed a mutation on the BRAF gene confirming the metastasis primitive origin. Treatment by surgical resection was performed palliatively. Comments: The diagnosis of an oral metastasis remains difficult and is based on the histological analysis and finding immune markers. Molecular biology is sometimes required for theranostics. Treatment options include surgical resection, radiotherapy, and/or chemotherapy. They are sometimes limited to preserve the quality of life. The prognosis of patients with oral metastases is very poor. Conclusion: Oral metastases are rare, and the diagnosis remains difficult