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.

Efficacy of an aloe vera, chamomile, and thyme cosmetic cream for the prophylaxis and treatment of mild dermatitis induced by radiation therapy in breast cancer patients (the Alantel study).

Objectives: Radiation-induced dermatitis (RD) is one of the most common toxicities in radiation therapy (RT) patients. Corticosteroids, immunosuppressants, and natural products (NPs) have been used as treatment. The objective was to evaluate the efficacy of a NPs-based cream (Alantel®) to reduce the incidence of RD in women with breast cancer undergoing RT treatment. Design: We conducted a controlled, randomized, double-blind clinical trial. Setting: Radiation Oncology Unit of the Reina Sofía Hospital and 5 Primary Care centers of the Cordoba and Guadalquivir Health District (Spain). Interventions: Patients assigned to the experimental group (GTA) were treated with Alantel, while those in the control group (GTE) were treated with a moisturizer and emollient cream. Main outcome measures: The primary outcome variable was the incidence of RD. RD-free time, duration of RD, quality of life, and product safety were also assessed. Results: Seventy patients were included in the study, 35 in the GTA and 35 in the GTE. The incidence of RD was lower in the GTA (71.4%) than in the GTE (91.4%) after 4 weeks of follow-up (RR = 0.78; NNT = 5; p < 0.031). The Skindex-29 questionnaire showed differences in the statement: "My skin condition makes it hard to work or do hobbies" (17.1% in the GTE vs. 2.9% in GTA; p = 0.024). Conclusions: The higher efficacy of Alantel® compared to the control cream in reducing the incidence of RD in women with breast cancer has been demonstrated.

Differences in molecular sensitization profiles between a Spanish and Latin American mite allergic patients.

BACKGROUND AND OBJECTIVE: To analyze the sensitization pattern to Dermatophagoides pteronyssinus and to associate the diagnostic findings and clinical severity in 218 allergic patients from two different continents. METHODS: Mite allergic patients were recruited by the Allergology departments from Latin America (n=88: Colombia, Costa Rica and Guatemala) and Spain (N=130). All patients had allergic rhinitis with or without asthma and positive skin prick test results to D. pteronyssinus. Specific IgE levels to D. pteronyssinus, D. farinae, Der p 1, Der p 2, and Der p 23 were quantified by ImmunoCAP system (ThermoFisher Scientific). Allergenic profile was also determined by western blot. Comparative Statistical analysis was performed by GraphPad software. RESULTS: Patients recognized most frequently Der p 2 (79%) followed by Der p 1 (73%), and Der p 23 (69%) allergens. The percentage of asthmatic patients increases with the number of sensitizations however none statistically significant differences were found. Interestingly, asthmatic patients presented the highest median levels of total IgE and specific IgE levels of D. pteronyssinus and molecular allergens, mainly Der p 2. Analysing the two different populations, Spanish patients were predominantly sensitized to Der p 2 (88.46%) and Der p 1 (83.84%), whereas Latin American population were more sensitized to Der p 23. CONCLUSION: Our data support the relevance of Der p 2 in mite allergy as the major allergen, with the high number of patients sensitized to it and its importance in the development of asthma. Sensitization to Der p 23 was more important in Latin America.

Circulating tumor DNA analysis of the phase III VOYAGER trial: KIT mutational landscape and outcomes in patients with advanced gastrointestinal stromal tumor treated with avapritinib or regorafenib.

BACKGROUND: The current treatment paradigm of imatinib-resistant metastatic gastrointestinal stromal tumor (GIST) does not incorporate KIT/PDGFRA genotypes in therapeutic drug sequencing, except for PDGFRA exon 18-mutant GIST that is indicated for avapritinib treatment. Here, circulating tumor DNA (ctDNA) sequencing was used to analyze plasma samples prospectively collected in the phase III VOYAGER trial to understand how the KIT/PDGFRA mutational landscape contributes to tyrosine kinase inhibitor (TKI) resistance and to determine its clinical validity and utility. PATIENTS AND METHODS: VOYAGER (N = 476) compared avapritinib with regorafenib in patients with KIT/PDGFRA-mutant GIST previously treated with imatinib and one or two additional TKIs (NCT03465722). KIT/PDGFRA ctDNA mutation profiling of plasma samples at baseline and end of treatment was assessed with 74-gene Guardant360® CDx. Molecular subgroups were determined and correlated with outcomes. RESULTS: A total of 386/476 patients with KIT/PDGFRA-mutant tumors underwent baseline (pre-trial treatment) ctDNA analysis; 196 received avapritinib and 190 received regorafenib. KIT and PDGFRA mutations were detected in 75.1% and 5.4%, respectively. KIT resistance mutations were found in the activation loop (A-loop; 80.4%) and ATP-binding pocket (ATP-BP; 40.8%); 23.4% had both. An average of 2.6 KIT mutations were detected per patient; 17.2% showed 4-14 different KIT resistance mutations. Of all pathogenic KIT variants, 28.0% were novel, including alterations in exons/codons previously unreported. PDGFRA mutations showed similar patterns. ctDNA-detected KIT ATP-BP mutations negatively prognosticated avapritinib activity, with a median progression-free survival (mPFS) of 1.9 versus 5.6 months for regorafenib. mPFS for regorafenib did not vary regardless of the presence or absence of ATP-BP/A-loop mutants and was greater than mPFS with avapritinib in this population. Secondary KIT ATP-BP pocket mutation variants, particularly V654A, were enriched upon disease progression with avapritinib. CONCLUSIONS: ctDNA sequencing efficiently detects KIT/PDGFRA mutations and prognosticates outcomes in patients with TKI-resistant GIST treated with avapritinib. ctDNA analysis can be used to monitor disease progression and provide more personalized treatment.

Influence of HER2 expression on prognosis in metastatic triple-negative breast cancer-results from an international, multicenter analysis coordinated by the AGMT Study Group.

BACKGROUND: Triple-negative breast cancer (TNBC) is associated with poor prognosis, and new treatment options are urgently needed. About 34%-39% of primary TNBCs show a low expression of human epidermal growth factor receptor 2 (HER2-low), which is a target for new anti-HER2 drugs. However, little is known about the frequency and the prognostic value of HER2-low in metastatic TNBC. PATIENTS AND METHODS: We retrospectively included patients with TNBC from five European countries for this international, multicenter analysis. Triple-negativity had to be shown in a metastatic site or in the primary breast tumor diagnosed simultaneously or within 3 years before metastatic disease. HER2-low was defined as immunohistochemically (IHC) 1+ or 2+ without ERBB2 gene amplification. Survival probabilities were calculated by the Kaplan-Meier method, and multivariable hazard ratios (HRs) were estimated by Cox regression models. RESULTS: In total, 691 patients, diagnosed between January 2006 and February 2021, were assessable. The incidence of HER2-low was 32.0% [95% confidence interval (CI) 28.5% to 35.5%], with similar proportions in metastases (n = 265; 29.8%) and primary tumors (n = 425; 33.4%; P = 0.324). The median overall survival (OS) in HER2-low and HER2-0 TNBC was 18.6 and 16.1 months, respectively (HR 1.00; 95% CI 0.83-1.19; P = 0.969). Similarly, in multivariable analysis, HER2-low had no significant impact on OS (HR 0.95; 95% CI 0.79-1.13; P = 0.545). No difference in prognosis was observed between HER2 IHC 0/1+ and IHC 2+ tumors (HR 0.89; 95% CI 0.69-1.17; P = 0.414). CONCLUSIONS: In this large international dataset of metastatic TNBC, the frequency of HER2-low was 32.0%. Neither in univariable nor in multivariable analysis HER2-low showed any influence on OS.

Spanish multidisciplinary consensus on the characteristics of severe asthma patients on biologic treatment who are candidates for at-home administration.

BACKGROUND AND OBJECTIVE: Biologic therapies are known to reduce exacerbations and improve severe uncontrolled asthma management. The at-home administration of biologics has increased during the COVID-19 pandemic, but the characteristics of severe uncontrolled asthma patients who may benefit from at-home administration of biologic therapy have yet to be identified. MATERIALS AND METHODS: This project is based on the Delphi method, designed to reach an expert consensus through a multidisciplinary scientific committee addressing the following questions: clinical characteristics, treatment adherence, patient or caregiver administration ability, patient self-care, relationship with the healthcare professional, patient preference, and access to the hospital. RESULTS: One hundred and thirty-one healthcare professionals (pulmonologists, allergists, nurses, and hospital pharmacists) completed two Delphi consensus questionnaires. Fourteen items were identified as priority characteristics, the first five being: 1. The patient follows the healthcare team's indications/recommendations to control their disease, 2. The patient is capable of detecting any deterioration in their disease and of identifying exacerbation triggers, 3. The patient receives biologic therapy and has stable disease with no vital risk, 4. The patient takes responsibility for their self-care, 5. The patient has occupational/educational obligations that prevent them from going to the hospital regularly. CONCLUSION: Disease stability and control plus the ability to identify exacerbation triggers are the most important characteristics when opting for at-home administration for a patient with severe uncontrolled asthma on biologic therapy. These recommendations could be applicable in clinical practice.

[Trifid median nerve. A rare anatomical variant in sonographic evaluation of carpal tunnel]. / Nervio mediano trífido. Una variante anatómica infrecuente en la exploración ecográfica del túnel del carpo.

The ultrasound study for the diagnosis of carpal tunnel syndrome can reveal different anatomical variants. A rare variant is the presence of a trifid median nerve. The visualization of this anatomical variant may be of importance in the surgical planning of carpal tunnel syndrome. Fifty-two-year-old male, with a clinic compatible with bilateral carpal tunnel syndrome. In the ultrasound examination, a bifid median nerve appears as a finding in the right wrist and a trifid median nerve in the left wrist as anatomical variants. It is important to distinguish a trifid median nerve from a persistent median artery at the level of the carpal tunnel, much more frequent than the first. For this, the ultrasound visualization of the study area using the Doppler function is essential.

Psychosocial risk in healthcare workers after one year of COVID-19.

BACKGROUND: The COVID-19 pandemic overwhelmed the capacity of the healthcare system, affecting the volume of demands and the care tasks of healthcare workers. AIMS: To examine the health indicators and exposure to psychosocial risks of Spanish healthcare workers 1 year into the COVID-19 pandemic and compare them with the results of the first wave. METHODS: We conducted a cross-sectional study using an online questionnaire (April-May 2020 and 2021). The data stem from the COTS 1 project database, corresponding to the first wave of COVID-19 (n = 1989) and COTS 2 (n = 1716) corresponding to 1 year later. The samples were independent. The prevalence of exposure to psychosocial risks and adverse health indicators was estimated for every occupational group, segregating the data by sex. RESULTS: Professionals of all types presented worse perception of health. In general, the results were worse for women, while geriatric assistants presented the greatest exposure to psychosocial risk in COTS 2 compared to COTS 1. Sleep problems, high quantitative demands and high concern about becoming infected and spreading COVID-19 were cross-disciplinary in COTS 1, while worse perception of health, high pace of work, high work-life conflict and low development opportunities stood out in COTS 2. CONCLUSIONS: Exposure to psychosocial risks was already high during the first wave and a significant decline in working conditions was observed. The prolongation of the pandemic exacerbated these results and seems to have multiplied the pre-existing inequalities between the axes of segregation in the labour market.

Bilateral pericapsular nerves group (PENG) block for analgesia in pediatric hip surgery.

Effective management and control of peri- and postoperative pain in hip surgery is essential in order to minimize the use of opioids and their adverse effects. Effective regional analgesia for hip pain is made particularly challenging by the complex innervation of the hip joint. Standard regional techniques can be associated with complications, including incomplete anesthesia, hypotension, or lower limb weakness. We present the case of a 5-year-old girl with a history of infantile cerebral palsy who underwent bilateral varus derotation osteotomy and adductor tenotomy due to paralytic dislocation. She received bilateral PENG block and femoral cutaneous nerve block-a simple technique that covers all the nerves involved in the sensory innervation of the joint capsule without the need for multiple injections.

Increased frequency of CD14+HLA-DR-/low cells in type 2 diabetes patients with poor glycemic control.

AIMS: Type 2 diabetes (T2DM) is associated with alterations of the immune response and T2DM patients have an increased risk for infections and certain sorts of cancers. Although CD14+HLA-DR-/low cells have emerged as important mediators of immunosuppression in several pathologies, including cancer and non-malignant diseases, the presence of these cells in T2DM is not fully characterized. METHODS: In this study, we evaluated the frequency of CD14+HLA-DR-/low cells in non-obese T2DM patients and their association with glycemic control. Peripheral blood mononuclear cells were isolated from healthy controls (HC, n = 24) and non-obese T2DM patients (n = 25), the population was evaluated by flow cytometry, and an analysis of correlation between cell frequencies and clinical variables was performed. RESULTS: CD14+HLA-DR-/low monocytes were expanded in patients with T2DM compared to HC regardless of weight. Among the subjects with T2DM, the frequency of CD14+HLA-DR-/low was higher in patients with poor glycemic control (HbA1c > 9%) compared to those with better glycemic control (HbA1c < 9%) and, positively correlated with the years since the diagnosis of T2DM, the age of the patients and the glycemic index. CONCLUSIONS: An increased frequency of CD14+HLA-DR-/low cells in the blood of T2DM patients was recorded. The influence of hyperglycemia seems to be independent of obesity, but related to glycemic control and age.

Nutritional management and clinical outcome of critically ill patients with COVID-19: A retrospective study in a tertiary hospital.

BACKGROUND & AIMS: Severe COVID-19 infection is characterized by an inflammatory response and lung injury that can evolve into an acute respiratory distress syndrome that needs support treatment in intensive care unit. Nutritional treatment is an important component of the management of critically ill patients and should be started in the first 48 h of ICU admission to avoid malnutrition. This study describes the characteristics of the patients treated in a tertiary hospital in Madrid during the months of March-May 2020 (first wave), the medical nutrition treatment employed and its influence in the clinical outcome of these patients. METHODS: This is a retrospective study including COVID-19 patients admitted in ICU that needed medical nutrition treatment (MNT). Collected variables included sex, age, BMI, underlying diseases, time from hospitalisation to ICU admission, type of respiratory support (invasive mechanical ventilation (IMV) or high flow nasal cannula (HFNC) or non-invasive ventilation (non-IMV)), caloric and protein requirements (25 kcal/kg adjusted body weight (ABW), 1.3 g/kg ABW/day), MNT type (enteral nutrition (EN), parenteral nutrition (PN), mixed EN + PN), total calories (including propofol) and proteins administered, percentage of caloric and protein goal in ICU day 4th and 7th, metabolic complications, acute kidney failure (AKF), length of stay (LOS) and mortality. Data are expressed as mean ± SD, median (IQR) or frequencies. Statistical analysis was performed with the IBM SPSS Statistics for Windows, Version 25.0. p < 0.05 were considered statistically significant. RESULTS: A total of 176 patients were included (72.7% male), 60.1 ± 13.5 years, BMI 29.9 ± 5.4 kg/m2. Underlying diseases included 47.4% overweight, 39.8% obesity, 49.1% hypertension, 41.4% dyslipidaemia. 88.6% of patients needed IMV, 89.1% prone position, 2.9% ECMO. Time to ICU admission: 2 (4.75) days. Estimated caloric and protein requirements were 1775 ± 202 kcal and 92.4 ± 10.3 g. Calories and proteins administered at days 4th and 7th were 1425 ± 577 kcal and 66 ± 26 g and 1574 ± 555 and 74 ± 37, respectively. Most of the patients received PN (alone or complementary to EN) to cover nutritional requirements (82.4% at day 4th and 77.9% at day 7th). IVM patients received more calories and proteins during the first week of ICU admission. Complications included 77.8% hyperglycaemia, 13.2% hypoglycaemia, 83.8% hypertriglyceridemia, and 35.1% AKF. ICU LOS was 20.5 (26) days. The mortality rate was 36.4%. CONCLUSIONS: In our series, the majority of patients reached energy and protein requirements in the first week of ICU admission due to the use of PN (total or complementary to EN). Patients with HFNC or non-IMV may be at risk of malnutrition if total or complementary PN to oral diet/ONS/tube feeding is not used to cover nutritional requirements. Therefore, if EN is not possible or insufficient, PN can be safely used in critically ill patients with COVID-19 with a close monitoring of metabolic complications.

Bilateral pericapsular nerves group (PENG) block for analgesia in pediatric hip surgery. / Bloqueo bilateral del grupo de nervios pericapsulares (PENG) como analgesia en cirugía de cadera infantil.

Effective management and control of peri- and postoperative pain in hip surgery is essential in order to minimize the use of opioids and their adverse effects. Effective regional analgesia for hip pain is made particularly challenging by the complex innervation of the hip joint. Standard regional techniques can be associated with complications, including incomplete anesthesia, hypotension, or lower limb weakness. We present the case of a 5-year-old girl with a history of infantile cerebral palsy who underwent bilateral varus derotation osteotomy and adductor tenotomy due to paralytic dislocation. She received bilateral PENG block and femoral cutaneous nerve block - a simple technique that covers all the nerves involved in the sensory innervation of the joint capsule without the need for multiple injections.

Analysis of outcomes of emergency general and gastrointestinal surgery during the COVID-19 pandemic.

BACKGROUND: Few surgical studies have provided adjusted comparative postoperative outcome data among contemporary patients with and without COVID-19 infection and patients treated before the pandemic. The aim of this study was to determine the impact of performing emergency surgery in patients with concomitant COVID-19 infection. METHODS: Patients who underwent emergency general and gastrointestinal surgery from March to June 2020, and from March to June 2019 in 25 Spanish hospitals were included in a retrospective study (COVID-CIR). The main outcome was 30-day mortality. Secondary outcomes included postoperative complications and failure to rescue (mortality among patients who developed complications). Propensity score-matched comparisons were performed between patients who were positive and those who were negative for COVID-19; and between COVID-19-negative cohorts before and during the pandemic. RESULTS: Some 5307 patients were included in the study (183 COVID-19-positive and 2132 COVID-19-negative during pandemic; 2992 treated before pandemic). During the pandemic, patients with COVID-19 infection had greater 30-day mortality than those without (12.6 versus 4.6 per cent), but this difference was not statistically significant after propensity score matching (odds ratio (OR) 1.58, 95 per cent c.i. 0.88 to 2.74). Those positive for COVID-19 had more complications (41.5 versus 23.9 per cent; OR 1.61, 1.11 to 2.33) and a higher likelihood of failure to rescue (30.3 versus 19.3 per cent; OR 1.10, 0.57 to 2.12). Patients who were negative for COVID-19 during the pandemic had similar rates of 30-day mortality (4.6 versus 3.2 per cent; OR 1.35, 0.98 to 1.86) and complications (23.9 versus 25.2 per cent; OR 0.89, 0.77 to 1.02), but a greater likelihood of failure to rescue (19.3 versus 12.9 per cent; OR 1.56, 95 per cent 1.10 to 2.19) than prepandemic controls. CONCLUSION: Patients with COVID-19 infection undergoing emergency general and gastrointestinal surgery had worse postoperative outcomes than contemporary patients without COVID-19. COVID-19-negative patients operated on during the COVID-19 pandemic had a likelihood of greater failure-to-rescue than prepandemic controls.

Modelling of photosynthesis, respiration, and nutrient yield coefficients in Scenedemus almeriensis culture as a function of nitrogen and phosphorus.

Photo-respirometric tecniques are applied for evaluating photosynthetic activity in phototrophic organisms. These methods allow to evaluate photosynthetic response under different conditions. In this work, the influence of nutrient availability (nitrate, ammonium, and phosphate) on the photosynthesis and respiration of Scenedesmus almeriensis was studied using short photo-respirometric measurements. Both photosynthesis and respiration increasing until saturation value and consecutively diminishing, presenting inhibition by high concentrations. Regarding the influence of phosphorus concentration in microalgae cells, a similar hyperbolic trend was observed but no inhibition was observed at high concentration. Based on these experimental data, the respiration, and the photosynthesis rate of S. almeriensis were modelled using Haldane equation for nitrate and ammonium data, and Monod equation for phosphate data. In addition, experiments were performed to determine the yield coefficients for both nitrogen and phosphorus in S. almeriensis cultures. The data showed that the nitrogen and phosphorous coefficient yields are not constant, being modified as a function of nutrients concentration, presenting the luxury uptake phenomena. Finally, the proposed models were incorporated into a simulation tool to evaluate the photosynthetic activity and the nutrient yield coefficients of S. almeriensis when different culture media and wastewaters are used as a nitrogen and phosphorous source for its growth. Key points • Microalgal photosynthesis/respiration vary as a function of nutrients availability. • Photosynthesis inhibition appears at high N-NO 3 - and N-NH4+ concentrations. • Nutrient yield coefficients are influenced by luxury uptake phenomenon.

Thermography for the differential diagnosis of vascular malformations.

Vascular malformations classification may pose a diagnostic challenge for physicians. In the early stages, they are diagnosed clinically mainly by visual inspection. For a deeper analysis, Doppler ultrasonography is the preferred technique to determine the haemodynamic behaviour of the anomaly. However, this imaging method is not always available and it requires trained operators to acquire and interpret the images. There is a lack of portable and user-friendly systems that may help physicians in the assessment of vascular malformations. We propose a new diagnostic procedure, more affordable and easier to use, based on a portable thermal camera. This technique provides information about temperature, which has been found to be correlated with the flow rate of the lesion. In our study, > 60 vascular malformations of previously diagnosed patients were analysed with a thermal camera to classify them into low-flow and high-flow malformations. The value was 1 for both sensitivity and specificity of this technique.

COVID-19 and the forgotten pandemic: follow-up of neurocognitive disorders during lockdown in Argentina. / COVID-19 y la pandemia olvidada: el seguimiento de las enfermedades neurocognitivas durante la cuarentena en Argentina.

INTRODUCTION: Health systems in numerous countries around the world are suffering a serious burden as a consequence of the COVID-19 pandemic. As a result of this situation, the follow-up of such chronic diseases as dementia may be at risk. Similarly, neuropsychiatric complications related to lockdown measures may also be neglected; Argentina's lockdown has been the longest implemented in Latin America. This study aims to determine the frequency of the different types of medical consultations for neurocognitive disorders and the predictors for requiring consultation since the beginning of the lockdown. METHODS: We performed a descriptive, observational, cross-sectional study based on data collected through an online survey. RESULTS: Data were collected on 324 participants, with 165 (50.9%) having had at least one medical consultation. Consultations were held by telephone in 109 cases (33.6%), by e-mail in 62 (19.1%), by video conference in 30 (9.3%), and at the emergency department in 23 (7.1%). Predictors of requiring consultation were Clinical Dementia Rating scores ≥1 (P<.001) and diagnosis of Alzheimer disease (P=.017). Higher Neuropsychiatric Inventory scores were found in the group of respondents who did require medical consultation (P<.001), but no significant differences were found between groups for Zarit Burden Interview scores. CONCLUSION: We identified a high prevalence of behavioural disorders and caregiver burden during lockdown. Nevertheless, only 50% of respondents had sought medical consultation (by telephone or email in 52.7% of cases). Care of people with dementia must be emphasised, guaranteeing follow-up of these patients.