Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group.

BACKGROUND: Advancements in the field of precision medicine have prompted the European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update the recommendations for the use of tumour next-generation sequencing (NGS) for patients with advanced cancers in routine practice. METHODS: The group discussed the clinical impact of tumour NGS in guiding treatment decision using the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) considering cost-effectiveness and accessibility. RESULTS: As for 2020 recommendations, ESMO recommends running tumour NGS in advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer. Moreover, it is recommended to carry out tumour NGS in clinical research centres and under specific circumstances discussed with patients. In this updated report, the consensus within the group has led to an expansion of the recommendations to encompass patients with advanced breast cancer and rare tumours such as gastrointestinal stromal tumours, sarcoma, thyroid cancer, and cancer of unknown primary. Finally, ESMO recommends carrying out tumour NGS to detect tumour-agnostic alterations in patients with metastatic cancers where access to matched therapies is available. CONCLUSION: Tumour NGS is increasingly expanding its scope and application within oncology with the aim of enhancing the efficacy of precision medicine for patients with cancer.

The AAHKS Clinical Research Award: Extended Postoperative Oral Tranexamic Acid in Total Knee Arthroplasty: A Randomized Controlled Pilot Study.

BACKGROUND: Perioperative tranexamic acid (TXA) use with total knee arthroplasty (TKA) is widely accepted today. Recently, a few international groups have published on the safety and outcomes of extending TXA use in the postoperative period. Through a double-blinded, randomized control trial (RCT), we aimed to investigate the safety and clinical efficacy of extended postoperative oral TXA use in TKA performed in an American, free-standing ambulatory surgery center (ASC). METHODS: Based on a power analysis, 40 patients undergoing primary TKA were randomized into 2 groups: extended oral TXA versus placebo. Both groups received a standard 1g intravenous TXA dose prior to incision and at the time of closure. The extended TXA group received an additional 1.95 g oral TXA dose following ambulation the day of surgery, plus on postoperative days 1,2, and 3. Patients who had a history of venous thromboembolism (VTE) or cancer were excluded. All patients received 81 mg of aspirin twice daily for VTE prophylaxis. Patients were followed on postoperative day 3 and weeks 2 and 6. Paired t-tests determined statistical significance. RESULTS: Extended TXA patients showed significantly increased knee flexion at 6 weeks (116.05 versus 106.5, P = .0308), improved VAS at 2 (2.5 versus 3.85, P = .039) and 6 weeks (1.35 versus 2.8, P = .011), and superior KOOS JR at 2 (66.87 versus 60.63, P = .03) and 6 weeks (73.33 versus 62.47, P = .0019) compared to placebo patients. No significant differences were found for changes in hemoglobin levels at any time points. No significant differences were found at 12 weeks for any clinical endpoints. No adverse events were noted in either cohort. CONCLUSIONS: When compared to placebo, the extended use of oral TXA in the postoperative period may safely result in improved motion, pain, and functional scores. Further investigation into 1-to-2-year outcomes, as well as the duration and dose of postoperative TXA use is warranted.

[Results of the treatment of irreparable rotator cuff ruptures with the use of the subacromial balloon]. / Resultados del tratamiento de roturas irreparables de manguito rotador con el uso del balón subacromial.

INTRODUCTION: arthroscopic surgical treatment of rotator cuff tendon injuries has replaced open surgery as the first treatment option. Different surgical techniques have been described for massive or irreparable ruptures, and recently, a new device that consists of a biodegradable subacromial spacer between the humeral head and the acromion has been used. The present study aims to analyse the results of this implant in our experience. MATERIAL AND METHODS: we conducted an observational and retrospective study of all patients undergoing subacromial spacer implantation at our centre from 2017 to 2019. Patients were assessed pre- and postoperatively using the Constant, DASH and VAS scales. RESULTS: a total of 43 patients met the inclusion criteria and the minimum follow-up of 24 months. The mean DASH scale score went from 53.6 at preoperative assessment to 27.9 at postoperative assessment (p = 0.026). There was also a significant improvement in the Constant scale from a mean of 37.9 to 61.8 (p = 0.037). In terms of pain assessment, the mean VAS went from a mean of 7.44 to 3.38 (p = 0.916). In 90% of patients no complications or need for further interventions were objectified. CONCLUSIONS: the subacromial balloon has shown favorable results in our series of patients, so it could be a valid treatment option in patients with non-repairable rotator cuff tears.

INTRODUCCIÓN: el tratamiento mediante cirugía artroscópica de las lesiones del manguito rotador ha desplazado a la cirugía abierta como primera opción de tratamiento. Existen diferentes técnicas quirúrgicas descritas para tratar las roturas masivas o no reparables. Desde hace unos años se viene utilizando un nuevo dispositivo que consiste en un balón subacromial biodegradable que actúa como espaciador entre la cabeza humeral y el acromion. Este trabajo pretende analizar los resultados de este implante. MATERIAL Y MÉTODOS: realizamos un estudio observacional y retrospectivo de todos los pacientes a los que se les implantó un balón subacromial en nuestro centro entre 2017 y 2019. Se evaluó a los pacientes pre y postoperatoriamente mediante las escalas de Constant, DASH y EVA. RESULTADOS: un total de 43 pacientes cumplieron los criterios de inclusión y el seguimiento mínimo de 24 meses. La puntuación media de la escala DASH pasó de 53.6 en la evaluación preoperatoria a 27.9 en la postoperatoria (p = 0.026). También se obtuvo una mejoría significativa en la escala de Constant, que pasó de una media de 37.9 a 61.8 (p = 0.037). En cuanto a la evaluación del dolor, la EVA media pasó de 7.44 a 3.38 (p = 0.916). En 90% de los pacientes no se objetivaron complicaciones ni necesidad de nuevas intervenciones. CONCLUSIONES: el balón subacromial ha mostrado resultados favorables en nuestra serie de pacientes, por lo que podría suponer una opción válida de tratamiento en pacientes con roturas no reparables del manguito rotador.

Perioperative Management of Comorbidities in Spine Surgery.

The number of spinal operations performed in the United States has significantly increased in recent years. Along with these rising numbers, there has been a corresponding increase in the number of patient comorbidities. The focus of this article is to review comorbidities in Spine surgery patients and outline strategies to optimize patients and avoid complications.

Effects of the use of raw or cooked chickpeas and the sausage cooking time on the quality of a lamb-meat, olive-oil emulsion-type sausage.

Reformulation of cooked sausages using high-protein plant-based food such as chickpea as meat extenders and vegetable oils to replace animal fat can be a suitable approach to promote the consumption of smaller portions of meat. The pre-processing of chickpea and the sausage cooking intensity can potentially affect the quality of reformulated sausages. In this study, an emulsion-type sausage made with lamb meat, chickpea and olive oil was prepared in triplicate following three different formulations containing the same targeted levels of protein (8.9%), lipids (21.5%), and starch (2.9%): control sausage (CON; control, without chickpea), and raw (RCP) and cooked chickpea (CCP) sausages (both with 7% chickpea). Sausages were cooked at 85 °C for two heating times (40 min or 80 min) and were analysed for weight loss, emulsion stability, colour, texture, lipid oxidation and volatile composition. Compared to CON sausages, the use of raw chickpea reduced the elasticity and significantly increased lipid oxidation during the sausage-making process resulting in major changes in the volatile composition. The use of previously cooked chickpea, however, resulted in the sausages having greater cooking loss, hardness and chewiness than CON sausages, while there was no difference in lipid oxidation, and differences in volatile compounds were scarce. The reformulation with cooked chickpea could provide a sausage with more similarity to the CON sausage. The extended heating time of 80 min at 85 °C did not significantly affect the quality traits in either CON or reformulated sausages except for a higher cooking loss.

Dietary administration of l-carnitine during the fattening period of early feed restricted lambs modifies lipid metabolism and meat quality.

Early feed restriction of lambs promotes a permanent mitochondrial dysfunction that impairs ß-oxidation of fatty acids along the whole life. Therefore, dietary l-carnitine might help to improve the mitochondrial function of these lambs, thus modifying lipid metabolism and meat quality traits. In order to test this hypothesis an experiment was carried out with 22 Merino lambs that were subjected to an early feed restriction during the suckling period. Once weaned, the lambs were allocated to a control group (CTRL, n = 11) being fed ad libitum a complete pelleted diet during the fattening phase, whereas the second group (CARN, n = 11) received the same diet formulated with 3 g/kg of l-carnitine. Carcass characteristics were not affected (P > 0.05) by treatment. However, lambs fed l-carnitine showed higher amounts of intramuscular fat (26.5 vs. 33.6 g/kg fresh matter; P = 0.047) with a lower ratio between polyunsaturated and saturated fatty acids (0.425 vs 0.333; P = 0.023) and a higher atherogenic (0.507 vs 0.597; P < 0.001) and thrombogenic index (1.23 vs 1.42; P < 0.001). An increase in lightness (P < 0.05) and a tendency to improved oxidative stability in cooked meat (P = 0.066) were also observed in the CARN group. Consequently, dietary l-carnitine supplied during the fattening period of early feed restricted lambs modifies meat quality traits thus increasing lightness, oxidative stability and intramuscular fat content, but worsening the fatty acid profile.

Germline-focused analysis of tumour-detected variants in 49,264 cancer patients: ESMO Precision Medicine Working Group recommendations.

BACKGROUND: The European Society for Medical Oncology Precision Medicine Working Group (ESMO PMWG) was reconvened to update its 2018/19 recommendations on follow-up of putative germline variants detected on tumour-only sequencing, which were based on an analysis of 17 152 cancers. METHODS: We analysed an expanded dataset including 49 264 paired tumour-normal samples. We applied filters to tumour-detected variants based on variant allele frequency, predicted pathogenicity and population variant frequency. For 58 cancer-susceptibility genes, we then examined the proportion of filtered tumour-detected variants of true germline origin [germline conversion rate (GCR)]. We conducted subanalyses based on the age of cancer diagnosis, specific tumour types and 'on-tumour' status (established tumour-gene association). RESULTS: Analysis of 45 472 nonhypermutated solid malignancy tumour samples yielded 21 351 filtered tumour-detected variants of which 3515 were of true germline origin. 3.1% of true germline pathogenic variants were absent from the filtered tumour-detected variants. For genes such as BRCA1, BRCA2 and PALB2, the GCR in filtered tumour-detected variants was >80%; conversely for TP53, APC and STK11 this GCR was <2%. CONCLUSION: Strategic germline-focused analysis can prioritise a subset of tumour-detected variants for which germline follow-up will produce the highest yield of most actionable true germline variants. We present updated recommendations around germline follow-up of tumour-only sequencing including (i) revision to 5% for the minimum per-gene GCR, (ii) inclusion of actionable intermediate penetrance genes ATM and CHEK2, (iii) definition of a set of seven 'most actionable' cancer-susceptibility genes (BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6 and RET) in which germline follow-up is recommended regardless of tumour type.

Prediction of patients with idiopathic generalized epilepsy from healthy controls using machine learning from scalp EEG recordings.

Epilepsy detection is essential for patients with epilepsy and their families, as well as for researchers and medical staff. The use of electroencephalogram (EEG) as a tool to support the diagnosis of patients with epilepsy is fundamental. Today, machine learning (ML) techniques are widely applied in neuroscience. The main objective of our study is to differentiate patients with idiopathic generalized epilepsy from healthy controls by applying machine learning techniques on interictal electroencephalographic recordings. Our research predicts which patients have idiopathic generalized epilepsy from a scalp EEG study. In addition, this study focuses on using the extreme gradient boosting (XGB) method applied to scalp EEG. XGB is one of the variants of gradient boosting and is a supervised learning algorithm. This type of system is developed to increase performance and processing speed. Through this proposed method, an attempt is made to recognize patterns from scalp EEG recordings that would allow the detection of IGE with high accuracy and differentiate IGE patients from healthy controls, creating an additional tool to support clinicians in their decision-making. Among the ML methods applied, the proposed XGB method achieves a better prediction of the distinct features in EEG signals from patients with IGE. XGB was 6.26% more accurate than the k-Nearest Neighbours method and was more accurate than the support vector machine (10.61%), decision tree (9.71%) and Gaussian Naïve Bayes (11.83%). Besides, the proposed XGB method showed the highest area under the curve (AUC 98%) and balanced accuracy (98.13%) of all methods tested. Application of ML technique in EEG of patients with epilepsy is very recent and is emerging with promising results. In this research work, we showed the usefulness of ML techniques to identify and predict generalized epilepsy from healthy controls in scalp EEG studies. These findings could help develop automated tools that integrate these ML techniques to assist clinicians in differentiating between patients with IGE from healthy controls in daily practice.

Incidence and Severity of Community- and Hospital-Acquired Hyponatremia in Pediatrics.

Hyponatremia is the most common electrolyte disturbance in hospitalized children, with a reported incidence of 15-30%, but its overall incidence and severity are not well known. The objective of our study was to determine the incidence, severity, and associated risk factors of community- and hospital-acquired hyponatremia on a general pediatric ward. Data of 5550 children admitted from June 2012 to December 2019 on plasma sodium and discharge diagnosis were analyzed by logistic regression model. Clinically relevant diagnostic groups were created. Hyponatremia was classified as mild, moderate, and severe. The incidence of community- and hospital-acquired hyponatremia was 15.8% and 1.4%, respectively. Most of the cases were mild (90.8%) to moderate (8.6%), with only two cases of severe community-acquired hyponatremia. There were no clinical complications in any of the hyponatremic children. Age and diagnosis at discharge were principal factors significantly correlated with hyponatremia. Community-acquired hyponatremia is more common than hospital-acquired hyponatremia in clinical practice. Severe cases of both types are rare. Children from 2 to 11 years of age presenting with infections, cardiovascular disorders, and gastrointestinal disorders are at risk of developing hyponatremia.

Severity of COVID-19 cases in the months of predominance of the Alpha and Delta variants.

New SARS-CoV-2 may pose problems in controlling the COVID-19 pandemic for public health. We aimed to assess and compare the symptoms and severity of cases due to the Alpha and Delta variant dominance periods, taking into account the effect of COVID-19 vaccination. A prospective epidemiological study of SARS-CoV-2 in Lleida was made to determine differences between Alpha and Delta variants periods. We assessed symptoms, specific comorbidities, sociodemographic information and vaccination status. Bivariate and logistic regression analyses were used to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CI) to investigate the relationship between symptoms and severity and the variants. Alpha variant period compared to the Delta showed an increased risk of ICU admission (aOR 2.0; 95% CI 1.2-2.3) and death (aOR 2.6; 95% CI 1.8-3.9) and cases were associated with people aged > 85 years (aOR 2.1; 95% CI 1.7-2.6) and partially vaccinated (aOR 5.6; 95% CI 3.2-9.9) and unvaccinated people (aOR 27.8; 95% CI 19.7-40.5). Fever, cough and vomiting were significantly associated with the Alpha variant compared to the Delta (aOR 1.6 (95% CI 1.5-1.7), 2.0 (95% CI 1.9-2.2) and 2.5 (95% CI 2.2-2.9, respectively). Our results show that the severity and profile of clinical symptoms varied according to the variant. The risk of ICU admission and death was higher in the Alpha period compared to the Delta as it affected the elderly and cases were less vaccinated.

Mortality predictors in patients with COVID-19 pneumonia: a machine learning approach using eXtreme Gradient Boosting model.

Recently, global health has seen an increase in demand for assistance as a result of the COVID-19 pandemic. This has prompted many researchers to conduct different studies looking for variables that are associated with increased clinical risk, and find effective and safe treatments. Many of these studies have been limited by presenting small samples and a large data set. Using machine learning (ML) techniques we can detect parameters that help us to improve clinical diagnosis, since they are a system for the detection, prediction and treatment of complex data. ML techniques can be valuable for the study of COVID-19, especially because they can uncover complex patterns in large data sets. This retrospective study of 150 hospitalized adult COVID-19 patients, of which we established two groups, those who died were called Case group (n = 53) while the survivors were Control group (n = 98). For analysis, a supervised learning algorithm eXtreme Gradient Boosting (XGBoost) has been used due to its good response compared to other methods because it is highly efficient, flexible and portable. In this study, the response to different treatments has been evaluated and has made it possible to accurately predict which patients have higher mortality using artificial intelligence, obtaining better results compared to other ML methods.

Effect of using a flax seed enriched concentrate on the fatty acid composition of omental fat in Pramenka lambs reared indoors.

This study was intended to determine the effect of adding flax seeds to a concentrate for lamb fattening on the fatty acid composition of the omental fat depot in Pramenka lambs reared indoors. A total of 63 lambs (10±3 kg of live body weight, 30±7 days of age, 30 males and 33 females) were used. They were divided into two groups: a control (CON) fed on hay, ewe's milk, and a 300-g daily ration of a commercial concentrate, and an experimental group (FS) fed on hay, ewe's milk and 300 g/day of the concentrate enriched with 5% of flax seeds. After a 60-day fattening period for each group, 10 lambs (5 males and 5 females) were selected and omental fat samples were analysed for fatty acid composition. Highly significant differences (p⟨0.001) were found between CON and FS in α-linolenic acid, the sum of n-3 fatty acids, and the ratio n-6/n-3 fatty acids. The effect of sex on the fatty acid content in the fat depot was only significant for C20:0 fatty acid (p⟨0.05).

Prevention of venous thromboembolism in hematologic neoplasms: an expert consensus from SEHH–SETH

Venous thromboembolism (VTE) is a serious complication in hematologic neoplasms, so finding adequate prevention strategies is an urgent requirement. However, prospective studies with large enough cohorts are scarce, limiting the development of evidence-based thromboprophylaxis guidelines. The present position paper is addressed to all hematologists treating patients affected by hematologic neoplasms with the aim to provide clinicians with a useful tool for the prevention of VTE.