The Covid-19 pandemic is changing the organization of healthcare and has a direct impact on digestive surgery. Healthcare priorities and circuits are being modified. Emergency surgery is still a ...priority. Functional surgery is to be deferred. Laparoscopic surgery must follow strict rules so as not to expose healthcare professionals (HCPs) to added risk. The question looms large in cancer surgery–go ahead or defer? There is probably an added risk due to the pandemic that must be balanced against the risk incurred by deferring surgery. For each type of cancer–colon, pancreas, oesogastric, hepatocellular carcinoma–morbidity and mortality rates are stated and compared with the oncological risk incurred by deferring surgery and/or the tumour doubling time. Strategies can be proposed based on this comparison. For colonic cancers T1-2, N0, it is advisable to defer surgery. For advanced colonic lesions, it seems judicious to undertake neoadjuvant chemotherapy and then wait. For rectal cancers T3-4 and/or N+, chemoradiotherapy is indicated, short radiotherapy must be discussed (followed by a waiting period) to reduce time of exposure in the hospital and to prevent infections. Most complex surgery with high morbidity and mortality–oesogastric, hepatic or pancreatic–is most often best deferred.
Background
In breast oncologic surgery, 75% of patients receive a postoperative opioid prescription at discharge, and 10%–20% will develop persistent opioid use. To inform future institutional ...guidelines, the objective of this study was to determine baseline opioid prescribing patterns in a single high‐volume, referral‐based breast center. We hypothesized that opioid prescribing practices varied between procedures and operating surgeons.
Methods
A retrospective analysis of all women undergoing breast cancer surgery between January and December 2019. Opioid prescriptions at discharge were converted to morphine milligram equivalents (MME). The primary outcome of interest was MME prescribed at discharge. Multiple linear regression was used to identify factors independently associated with MME prescribed.
Results
392 patients met inclusion criteria; 68.3% underwent partial mastectomy. Median age was 61 (interquartile range IQR 51–70). Median MME prescribed at discharge was 112.5 (IQR 75–150); 83.9% of patients were prescribed co‐analgesia. The prescriber was a trainee in 37.7% of cases. 15 patients (3.8%) required opioid renewal. On multivariate analysis, axillary procedure was associated with increased MME (ß = 17, 95% CI 5.5–28 and ß = 32, 95% CI 17–47, for sentinel node and axillary dissection, respectively). However, the factor with the greatest impact on MME was operating surgeon (ß = 72, 95% CI 58–87). Residents prescribed less MME compared to attending surgeons (ß = 11, 95% CI −22; −0.06).
Conclusion
In a tertiary care center, the operating surgeon had the greatest influence on opioid prescribing practices, and trainees tended to prescribe less MME. These findings support the need for a standardized approach to optimize prescribing and reduce opioid‐related harms after oncologic breast surgery.
Synopsis
In this study of opioid prescribing practices following breast oncologic surgery, the operating surgeon has the greatest impact on opioid prescriptions, and trainees tend to prescribe less than attendings, supporting the need for standardized prescribing practices following breast cancer surgery.
We present the results of observations taken with the X-shooter spectrograph devoted to the study of quasars at z ∼ 6. This paper focuses on the properties of metals at high redshift traced, in ...particular, by the C iv doublet absorption systems. Six objects were observed with resolutions 27 and 34 km s−1 in the visual, and 37.5 and 53.5 km s−1 in the near-infrared. We detected 102 C iv lines in the range: 4.35 < z < 6.2 of which 27 are above z ∼ 5. Thanks to the characteristics of resolution and spectral coverage of X-shooter, we could also detect 25 Si iv doublets associated with the C iv at z 5. The column density distribution function of the C iv line sample is observed to evolve in redshift for z 5.3, with respect to the normalization defined by low-redshift (1.5 < z < 4) C iv lines. This behaviour is reflected in the redshift evolution of the C iv cosmic mass density,
, of lines with column density in the range
, which is consistent with a drop of a factor of ∼2 for z 5.3. Considering only the stronger C iv lines (
),
gently rises by a factor of ∼10 between z 6.2 and z 1.5 with a possible flattening towards z ∼ 0. The increase is well fitted by a power law:
. An insight into the properties of the C iv absorbers and their evolution with redshift is obtained by comparing the observed column densities of associated C iv, Si iv and C ii absorptions with the output of a set of cloudy photoionization models. As already claimed by cosmological simulations, we find that C iv is a good tracer of the metallicity in the low-density intergalactic medium (IGM) gas at z ∼ 5-6 while at z ∼ 3 it arises in gas with overdensity δ ∼ 100.
The 2021 Tajogaite eruption of Cumbre Vieja (La Palma, Spain) was typified by the emission of low viscosity lavas that flowed at high velocities and inundated a large area. We experimentally ...investigated the rheological evolution of melt feeding the eruption through concentric cylinder viscometry to understand the exceptional flowing ability of these lavas and constrain its emplacement dynamics. We conducted a set of cooling deformation experiments at different cooling rates (from 0.1 to 10 °C/min), and isothermal deformation experiments at subliquidus dwell temperatures between 1225 and 1175°C. All experiments were conducted at a shear rate of 10 s−1. Results show that disequilibrium crystallization and its timescale fundamentally control the rheological evolution of the melt, resulting in different rheological response to deformation of the crystal‐bearing magmatic suspension. Integrating rheological data with field observations allows us to shed light on the mechanisms that govern the high flowability of these lavas.
Plain Language Summary
Understanding and modeling the mechanisms controlling the inundation ability of lava flows is pivotal for hazard assessment and mitigation of related risk. Lavas flowing across the Earth's surface experience different cooling conditions. These conditions are related to the thermal gradients generated at various levels within the flow's thickness. Especially for extremely fluid magmas such as those erupted at Cumbre Vieja, the different cooling paths (and different disequilibrium conditions) that lava flows experience strongly influence the crystallization processes. Both cooling and crystallization produce an increase of lava viscosity, hindering lava flowability. If crystallization occurs over timescales shorter than those of cooling, the presence of crystals may give rise to more complex flow behavior and emplacement style, including flow rupture and separation. Such conditions may favor the development of flow decoupling and lava tunnel formation. In this study we experimentally investigate the viscosity evolution of the Tajogaite lavas and the transition from pure viscous flow to more complex responses to deformation. Then, we use our data set in concert with field observation to constrain the dynamics governing the emplacement style of these lavas.
Key Points
High‐T deformation experiments characterize the rheology of Cumbre Vieja lavas under both disequilibrium and equilibrium conditions
Two different rheological responses are observed in relation to the increased disequilibrium conditions at which the melt is subjected
Integration of experimental and field data permits to understand the mechanisms that enhance the flowing ability of these lavas
The predictive value of KRAS mutation in metastatic colorectal cancer (MCRC) patients treated with cetuximab plus chemotherapy has recently been suggested. In our study, 59 patients with a ...chemotherapy-refractory MCRC treated with cetuximab plus chemotherapy were included and clinical response was evaluated according to response evaluation criteria in solid tumours (RECIST). Tumours were screened for KRAS mutations using first direct sequencing, then two sensitive methods based on SNaPshot and PCR-ligase chain reaction (LCR) assays. Clinical response was evaluated according to gene mutations using the Fisher exact test. Times to progression (TTP) were calculated using the Kaplan-Meier method and compared with log-rank test. A KRAS mutation was detected in 22 out of 59 tumours and, in six cases, was missed by sequencing analysis but detected using the SNaPshot and PCR-LCR assays. Remarkably, no KRAS mutation was found in the 12 patients with clinical response. KRAS mutation was associated with disease progression (P=0.0005) and TTP was significantly decreased in mutated KRAS patients (3 vs 5.5 months, P=0.015). Our study confirms that KRAS mutation is highly predictive of a non-response to cetuximab plus chemotherapy in MCRC and highlights the need to use sensitive molecular methods, such as SNaPshot or PCR-LCR assays, to ensure an efficient mutation detection.
Open‐conduit conditions characterize several of the most hazardous and active volcanic systems of basaltic composition worldwide, persistently refilled by magmatic inputs. Eruptive products with ...similar bulk compositions, chemically buffered by continual mafic inputs, nevertheless exhibit heterogeneous glass compositions in response to variable magma mixing, crystallization, and differentiation processes within different parts of the plumbing system. Here, we document how multivariate statistics and magma differentiation modeling based on a large data set of glass compositions can be combined to constrain magma differentiation and plumbing system dynamics. Major and trace elements of matrix glasses erupted at Stromboli volcano (Italy) over the last 20 years provide a benchmark against which to test our integrated petrological approach. Principal component analysis, K‐means cluster analysis, and kernel density estimation reveal that trace elements define a multivariate space whose eigenvectors are more readily interpretable in terms of petrological processes than major elements, leading to improved clustering solutions. Comparison between open‐ and closed‐system differentiation models outlines that steady state magma compositions at constantly replenished and erupting magmatic systems approximate simple fractional crystallization trends, due to short magma residence times. Open‐system magma evolution is associated with magma storage crystallinities that are lower than those associated with closed‐system scenarios. Accordingly, open‐system dynamics determine the efficient crystal‐melt separation toward the top of the reservoir, where eruptible melts continuously supply the ordinary activity. Conversely, a mush‐like environment constitutes the bottom of the reservoir, where poorly evolved magmas result from mixing events between mush residual melts and primitive magmas injected from deeper crustal levels.
Plain Language Summary
Volcanoes characterized by continuous eruptive activity are typified by constant replenishment of new magma, rising from deeper regions of the crust. The volcanic glass (supercooled silicate melt), represents the residual liquid of magma crystallization, and is found as the intracrystalline matrix of eruptive products. The study of its chemical composition may provide insight into the processes occurring at depths beneath the volcanic vent, where magma compositional changes result from crystallization and mixing with new magma rising from depth. We combine statistical analyses and analytical equations based on the chemical composition of the matrix glasses from Stromboli volcano, in order to constrain the processes which produce their chemical variations, identifying different environments where magmas are stored at depth. Our results also show that when magma is stored for a short period of time, the chemical changes to which the magma is subjected in a constantly replenished system are similar to those occurring in a system which is closed to new inputs of magma.
Key Points
The combination of multivariate statistics with geochemical modeling provides new constraints on magma differentiation processes
Multivariate statistics based on trace elements allow better retrieval of petrological information than those based on major elements
Magma differentiation in open systems approximates that occurring in closed systems when magma residence timescales are short
Small bowel adenocarcinoma (SBA) is a rare tumour with a poor prognosis. Molecular biology data on SBA carcinogenesis are lacking.
Expression of HER2, β-catenin, p53 and mismatch repair (MMR) protein ...was assessed by immunohistochemistry. KRAS, V600E BRAF mutations and microsatellite instability were investigated.
We obtained samples from 63 SBA patients (tumour stages: I-II: 30%; III: 35%; IV: 32%; locally advanced: 3%). HER2 overexpression (3+) was observed in 2 out of 62 patients, overexpression of p53 in 26 out of 62, abnormal expression of β-catenin in 12 out of 61, KRAS mutation in 21 out of 49, BRAF V600E mutation in 1 out of 40 patients, MMR deficiency (dMMR) in 14 out of 61 and was consistent with Lynch syndrome in 9 out of 14 patients. All of the dMMR tumours were in the duodenum or jejunum and only one was stage IV. Median overall survival (OS) was 36.6 months (95% CI, 26.9-72.2). For all patients, in univariate analysis, stages I-II (P<0.001), WHO PS 0-1 (P=0.01) and dMMR phenotype (P=0.02) were significantly associated with longer OS. In multivariate analysis, disease stage (P=0.01) and WHO PS 0-1 (P=0.001) independently predicted longer OS. For stage IV patients, median OS was 20.5 months (95% CI: 14.6; 36.6 months). In multivariate analysis, WHO PS 0-1 (P=0.0001) and mutated KRAS status (P=0.02) independently predicted longer OS.
This large study suggests that molecular alterations in SBA are closer to those in colorectal cancer (CRC) than those in gastric cancer, with low levels of HER 2 overexpression and high frequencies of KRAS mutations. The seemingly higher frequency of dMMR than in CRC may be explained by the higher frequency of Lynch syndrome in SBA patients. A dMMR phenotype was significantly associated with a non-metastatic tumour (P=0.02). A trend for a good prognosis and a duodenum or jejunum primary site was associated with dMMR.
The well-being of dogs can be affected by changes in human lifestyle, eating habits and increased stressors that lead to behavioural disorders including fear, hyperactivity and anxiety, followed by ...negative affective moods and poor welfare. This randomised, controlled clinical evaluation involved 69 dogs, 38 males and 31 females, of different breeds, with behavioural disorders related to anxiety and chronic stress. They were fed a control diet or a nutraceutical diet (ND group) for 45 days. Neuroendocrine (serotonin, dopamine, β-endorphins, noradrenaline and cortisol) and stress (derivatives of reactive oxygen metabolites (dROMs) and biological antioxidant potential (BAP)) parameters related to behavioural disorders were evaluated at the beginning and end of the study period. Results showed a significant increase in serotonin, dopamine and β-endorphins plasma concentrations (*P<0.05, *P<0.05 and **P<0.01, respectively) and a significant decrease in noradrenaline and cortisol plasma concentrations in the ND group (*P<0.05). dROMs significantly decreased in the ND group (*P<0.05) while BAP was not affected. This study demonstrated for the first time that a specific diet significantly and positively affected neuroendocrine parameters and dROMs. These results open significant perspectives concerning the use of diet and nutraceuticals in the treatment of behavioural disorders.
Since 2004, the clinical impact of monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR) on patients with metastatic colorectal cancer (MCRC) has been clearly ...established. The combination of these biological agents with conventional chemotherapy has led to a significant improvement in response rate, progression-free survival and overall survival in first-line as well as in second- or third-line treatment of MCRC. However, the high variability of response and outcome in MCRC patients treated with these anti-EGFR mAbs has highlighted the need of identifying clinical and/or molecular predictive markers to ensure appropriate use of targeted therapies. The presence of somatic KRAS mutations has been clearly identified as a predictive marker of resistance to anti-EGFR in MCRC, and the use of anti-EGFR mAbs is now restricted to patients with no detectable KRAS mutation. Several studies have indicated that amplification of EGFR, overexpression of the EGFR ligands and inactivation of the anti-oncogene TP53 are associated with sensitivity to anti-EGFR mAbs, whereas mutations of BRAF and PIK3CA and loss of PTEN expression are associated with resistance. Besides these somatic variations, germline polymorphisms such as those affecting genes involved in the EGFR pathway or within the immunoglobulin receptors may also modulate response to anti-EGFR mAbs. Until now, all these markers are not completely validated and only KRAS genotyping is mandatory in routine practice for use of the anti-EGFR mAbs in MCRC.
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