Clinical characteristic and survival outcomes of patients with advanced NSCLC according to KRAS mutational status in the French real-life ESME cohort.

PURPOSE: The RAS/MEK signaling pathway is essential in carcinogenesis and frequently altered in non-small-cell lung cancer (NSCLC), notably by KRAS mutations (KRASm) that affect 25%-30% of non-squamous NSCLC. This study aims to explore the impact of KRASm subtypes on disease phenotype and survival outcomes. PATIENTS AND METHODS: We conducted a retrospective analysis of the French Epidemiological Strategy and Medical Economics database for advanced or metastatic lung cancer from 2011 to 2021. Patient demographics, histology, KRASm status, treatment strategies, and outcomes were assessed. RESULTS: Of 10 177 assessable patients for KRAS status, 17.6% had KRAS p.G12C mutation, 22.6% had KRAS non-p.G12C mutation, and 59.8% were KRASwt. KRASm patients were more often smokers (96.3%) compared with KRASwt (85.8%). A higher proportion of programmed death-ligand 1 ≥50% was found for KRASm patients: 43.5% versus 38.0% (P < 0.01). KRASm correlated with poorer outcomes. First-line median progression-free survival was shorter in the KRASm than the KRASwt cohort: 4.0 months [95% confidence interval (CI) 3.7-4.3 months] versus 5.1 months (95% CI 4.8-5.3 months), P < 0.001. First-line overall survival was shorter for KRASm than KRASwt patients: 12.6 months (95% CI 11.6-13.6 months) versus 15.4 months (95% CI 14.6-16.2 months), P = 0.012. First-line chemoimmunotherapy offered better overall survival in KRAS p.G12C (48.8 months) compared with KRAS non-p.G12C (24.0 months) and KRASwt (22.5 months) patients. Second-line overall survival with immunotherapy was superior in the KRAS p.G12C subgroup: 12.6 months (95% CI 8.1-18.6 months) compared with 9.4 months (95% CI 8.0-11.4 months) for KRAS non-p.G12C and 9.6 months (8.4-11.0 months) for KRASwt patients. CONCLUSION: We highlighted distinct clinical profiles and survival outcomes according to KRASm subtypes. Notably KRAS p.G12C mutations may provide increased sensitivity to immunotherapy, suggesting potential therapeutic implications for sequencing or combination of therapies. Further research on the impact of emerging KRAS specific inhibitors are warranted in real-world cohorts.

Prognosis of acute heart failure based on clinical data of congestion.

BACKGROUND AND OBJECTIVES: This work aims to assess whether symptoms/signs of congestion in patients with acute heart failure (AHF) evaluated in hospital emergency departments (HED) allows for predicting short-term progress. PATIENTS AND METHODS: The study group comprised consecutive patients diagnosed with AHF in 45 HED from EAHFE Registry. We collected clinical variables of systemic congestion (edema in the lower extremities, jugular vein distention, hepatomegaly) and pulmonary congestion (dyspnea on exertion, paroxysmal nocturnal dyspnea, orthopnea, and pulmonary crackles) and analysed their individual and group association with all-cause 30-day of mortality crudely and adjusted for differences between groups. RESULTS: We analysed 18,120 patients (median = 83 years, interquartile range [IQR] = 76-88; women = 55.7%). Of them, 44.6% had > 3 congestive symptoms/signs. Individually, the 30-day adjusted risk of death increased 14% for jugular vein distention (hazard ratio [HR] = 1.14, 95% confidence interval [95%CI] = 1.01-1.28) and 96% for dyspnea on exertion (HR = 1.96, 95% CI = 1.55-2.49). Assessed jointly, the risk progressively increased with the number of symptoms/signs present; compared to patients without symptoms/signs of congestion, the risk increased by 109%, 123 %, and 156% in patients with 1-2, 3-5, and 6-7 symptoms/signs, respectively. These associations did not show interaction with the final disposition of the patient after their emergency care (discharge/hospitalization) with the exception of edema in the lower extremities, which had a better prognosis in discharged patients (HR = 0.66, 95% CI = 0.49-0.89) than hospitalised patients (HR = 1.01, 95% CI = 0.65-1.57; interaction p < 0.001). CONCLUSION: The presence of a greater number of congestive symptoms/signs was associated with greater all-cause 30-day mortality. Individually, jugular vein distention and dyspnea on exertion were associated with higher short-term mortality.

Alcohol, health and cardiovascular disease.

Recent epidemiological studies have shown that alcohol consumption can increase the risk of arterial hypertension, atrial fibrillation and gastrointestinal and breast cancer. Various sectors are therefore promoting abstinence from alcohol. However, light alcohol consumption has once again been shown to reduce the risk of myocardial infarction and diabetes but with an unclear effect on cerebrovascular disease. The decision to consume alcohol should therefore be an individual one based on personal factors. A level of consumption <100 g/week for men (less for women) appears not to increase all-cause mortality, while high consumption or binge drinking significantly increases mortality risk. All measures to prevent this type of consumption, especially among the younger population, should therefore be applied. There are data indicating an advantage of wine over other beverages, but they are not conclusive.

Consensus on improving the comprehensive care of patients with acute heart failure.

The latest acute heart failure (AHF) consensus document from the Spanish Society of Cardiology (SEC, for its initials in Spanish), Spanish Society of Internal Medicine (SEMI), and Spanish Society of Emergency Medicine (SEMES) was published in 2015, which made an update covering the main novelties regarding AHF from the last few years necessary. These include publication of updated European guidelines on HF in 2016, new studies on the pharmacological treatment of patients during hospitalization, and other recent developments regarding AHF such as early treatment, intermittent treatment, advanced HF, and refractory congestion. This consensus document was drafted with the aim of updating all aspects related to AHF and to create a document that comprehensively describes the diagnosis, treatment, and management of this disease.

Current status and needs for changes in critical care training: the voice of the young cardiologists.

AIMS: The implementation of the 2013 European Society of Cardiology (ESC) Core Curriculum guidelines for acute cardiovascular care (acc) training among European countries is unknown. We aimed to evaluate the current status of acc training among cardiology trainees and young cardiologists (<40 years) from ESC countries. METHODS AND RESULTS: The survey (March-July 2019) asked about details of cardiology training, self-confidence in acc technical and non-technical skills, access to training opportunities, and needs for further training in the field. Overall 614 young doctors, 31 (26-43) years old, 55% males were surveyed. Place and duration of acc training differed between countries and between centres in the same country. Although the majority of the respondents (91%) had completed their acc training, the average self-confidence to perform invasive procedures and to manage acc clinical scenarios was low-44% (27.3-70.4). The opportunities for simulation-based learning were scarce-18% (5.8-51.3), as it was previous leadership training (32%) and knowledge about key teamwork principles was poor (48%). The need for further acc training was high-81% (61.9-94.3). Male gender, higher level of training centres, professional qualifications of respondents, longer duration of acc/intensive care training, debriefings, and previous leadership training as well as knowledge about teamwork were related to higher self-confidence in all investigated aspects. CONCLUSIONS: The current cardiology training program is burdened by deficits in acc technical/non-technical skills, substantial variability in programs across ESC countries, and a clear gender-related disparity in outcomes. The forthcoming ESC Core Curriculum for General Cardiology is expected to address these deficiencies.

Consensus on improving the comprehensive care of patients with acute heart failure. / Consenso para la mejora de la atención integral de los pacientes con insuficiencia cardíaca aguda.

The latest acute heart failure consensus document from the Spanish Society of Cardiology, Spanish Society of Internal Medicine, and Spanish Society of Emergency Medicine was published in 2015, which made an update covering the main novelties regarding acute heart failure from the last few years necessary. These include publication of updated European guidelines on heart failure in 2016, new studies on the pharmacological treatment of patients during hospitalization, and other recent developments regarding acute heart failure such as early treatment, intermittent treatment, advanced heart failure, and refractory congestion. This consensus document was drafted with the aim of updating all aspects related to acute heart failure and to create a document that comprehensively describes the diagnosis, treatment, and management of this disease.

Alcohol, health and cardiovascular disease. / Alcohol, salud y enfermedad cardiovascular.

Recent epidemiological studies have shown that alcohol consumption can increase the risk of arterial hypertension, atrial fibrillation and gastrointestinal and breast cancer. Various sectors are therefore promoting abstinence from alcohol. However, light alcohol consumption has once again been shown to reduce the risk of myocardial infarction and diabetes but with an unclear effect on cerebrovascular disease. The decision to consume alcohol should therefore be an individual one based on personal factors. A level of consumption <100g/week for men (less for women) appears not to increase all-cause mortality, while high consumption or binge drinking significantly increases mortality risk. All measures to prevent this type of consumption, especially among the younger population, should therefore be applied. There are data indicating an advantage of wine over other beverages, but they are not conclusive.

First hospital admission due to heart failure: In-hospital mortality and patient profile. / Primera hospitalización por insuficiencia cardiaca: mortalidad hospitalaria y perfil del paciente.

OBJECTIVES: We evaluated the patient profile and outcomes of first heart failure (HF) related hospital admission patients in the 2010-2014 period. DESIGN: Retrospective, single-centre, cohort study. SETTING: We used administrative data from a tertiary care hospital (Hospital Universitari de Bellvitge, Barcelona, Spain). PARTICIPANTS: All patients with primary diagnosis of HF registered at the hospital discharge database from 2010 to 2014 were included, ruling out that HF was present 10 years prior to the current episode. INTERVENTION: Primary care HF diagnosis status was assessed in order to distinguish new onset from no-new onset patients. MAIN MEASURES: Descriptive, bivariate and multivariate analysis were performed using age, previous primary care HF diagnosis and in-hospital death as grouping variables. Significant variables were fitted into a Linear logistic regression model for each outcome. RESULTS: We selected 3,868 first HF-related admissions (56.8% of all HF episodes). In 1,220 patients (31.7%) HF was diagnosed by their primary care physician. Main pattern was a woman (OR=2.4), with higher prevalence of hypertension (OR=1.7), atrial fibrillation (OR=1.3), chronic kidney disease (OR=1.6) and mortality rate (9.8%). In-hospital death rate was 5.8%, age over 85 (OR=5.57), chronic kidney disease (OR=1.44) and length of stay over 7 days (OR=1.90) being the main contributors. CONCLUSIONS: First HF related admissions account for 56.7% of all HF episodes. Roughly one third of patients were already diagnosed by the time of their first hospital admission. Elderly women were the most frequent, but not the only, group of patients. Age, hospital stay and chronic kidney disease were the main contributors for in-hospital death.

Acute heart failure and cardiogenic shock: a multidisciplinary practical guidance.

PURPOSE: Acute heart failure (AHF) causes high burden of mortality, morbidity, and repeated hospitalizations worldwide. This guidance paper describes the tailored treatment approaches of different clinical scenarios of AHF and CS, focusing on the needs of professionals working in intensive care settings. RESULTS: Tissue congestion and hypoperfusion are the two leading mechanisms of end-organ injury and dysfunction, which are associated with worse outcome in AHF. Diagnosis of AHF is based on clinical assessment, measurement of natriuretic peptides, and imaging modalities. Simultaneously, emphasis should be given in rapidly identifying the underlying trigger of AHF and assessing severity of AHF, as well as in recognizing end-organ injuries. Early initiation of effective treatment is associated with superior outcomes. Oxygen, diuretics, and vasodilators are the key therapies for the initial treatment of AHF. In case of respiratory distress, non-invasive ventilation with pressure support should be promptly started. In patients with severe forms of AHF with cardiogenic shock (CS), inotropes are recommended to achieve hemodynamic stability and restore tissue perfusion. In refractory CS, when hemodynamic stabilization is not achieved, the use of mechanical support with assist devices should be considered early, before the development of irreversible end-organ injuries. CONCLUSION: A multidisciplinary approach along the entire patient journey from pre-hospital care to hospital discharge is needed to ensure early recognition, risk stratification, and the benefit of available therapies. Medical management should be planned according to the underlying mechanisms of various clinical scenarios of AHF.

Can meteorological factors forecast asthma exacerbation in a paediatric population?

BACKGROUND: Asthma exacerbations attended in emergency departments show a marked seasonality in the paediatric age. This seasonal pattern can change from one population to another and the factors involved are poorly understood. OBJECTIVES: To evaluate the association between meteorological factors and schooling with asthma exacerbations in children attended in the paediatric emergency department of a district hospital. METHODS: We conducted a retrospective review of the medical records of children 5-14 years of age attended for asthma exacerbations during a 4-year period (2007-2011). Climatic data were obtained from a weather station located very close to the population studied. The number of asthma exacerbations was correlated to temperature, barometric pressure, relative humidity, rainfall, wind speed, wind distance, solar radiation, water vapour pressure and schooling, using regression analyses. RESULTS: During the study period, 371 children were attended for asthma exacerbations; median age was eight years (IQR: 6-11), and 59% were males. Asthma exacerbations showed a bimodal pattern with peaks in spring and summer. Maximum annual peak occurred in week 39, within 15 days from school beginning after the summer holidays. A regression model with mean temperature, water vapour pressure, relative humidity, maximum wind speed and schooling could explain 98.4% (p<0.001) of monthly asthma exacerbations. CONCLUSIONS: The combination of meteorological factors and schooling could predict asthma exacerbations in children attended in a paediatric emergency department.

Solar radiation and water vapor pressure to forecast chickenpox epidemics.

The clear seasonality of varicella infections in temperate regions suggests the influence of meteorologic conditions. However, there are very few data on this association. The aim of this study was to determine the seasonal pattern of varicella infections on the Mediterranean island of Mallorca (Spain), and its association with meteorologic conditions and schooling. Data on the number of cases of varicella were obtained from the Network of Epidemiologic Surveillance, which is composed of primary care physicians who notify varicella cases on a compulsory basis. From 1995 to 2012, varicella cases were correlated to temperature, humidity, rainfall, water vapor pressure, atmospheric pressure, wind speed, and solar radiation using regression and time-series models. The influence of schooling was also analyzed. A total of 68,379 cases of varicella were notified during the study period. Cases occurred all year round, with a peak incidence in June. Varicella cases increased with the decrease in water vapor pressure and/or the increase of solar radiation, 3 and 4 weeks prior to reporting, respectively. An inverse association was also observed between varicella cases and school holidays. Using these variables, the best fitting autoregressive moving average with exogenous variables (ARMAX) model could predict 95 % of varicella cases. In conclusion, varicella in our region had a clear seasonality, which was mainly determined by solar radiation and water vapor pressure.

Are hospitalizations for rotavirus gastroenteritis associated with meteorologic factors?

Local climatic factors might explain seasonal patterns of rotavirus infections, but few models have been proposed to determine the effects of weather conditions on rotavirus activity. Here, we study the association of meteorologic factors with rotavirus activity, as determined by the number of children hospitalized for rotavirus gastroenteritis on the Mediterranean island of Mallorca (Spain). We conducted a retrospective review of the medical records of children aged 0-5 years admitted for rotavirus gastroenteritis between January 2000 and December 2010. The number of rotavirus hospitalizations was correlated to temperature, humidity, rainfall, atmospheric pressure, water vapor pressure, wind speed, and solar radiation using regression and time-series techniques. A total of 311 patients were hospitalized for rotavirus gastroenteritis in the 11-year study period, with a seasonal pattern from December to June, and a peak incidence in February. After multiple regressions, weekly rotavirus activity could be explained in 82 % of cases (p < 0.001) with a one-week lag meteorologic model. Rotavirus activity was negatively associated to temperature and positively associated to atmospheric pressure, solar radiation, and wind speed. Temperature and solar radiation were the factors that contributed most to the model, with a peak rotavirus activity at 9 °C and 800 10KJ/m(2), respectively. In conclusion, hospitalization for rotavirus was strongly associated with mean temperature, but an association of rotavirus activity with solar radiation, atmospheric pressure, and wind speed was also demonstrated. This model predicted more than 80 % of rotavirus hospitalizations.

Trends in death attributed to myocardial infarction, heart failure and pulmonary embolism in Europe and Canada over the last decade.

BACKGROUND: Worldwide, cardiovascular diseases and cancer account for ∼40% of deaths. Certain reports have shown a progressive decrease in mortality. Our main objective was to assess mortality trends related to myocardial infarction (MI), heart failure (HF) and pulmonary embolism (PE). METHODS: MI, HF and PE were studied as cause of death based on the analysis of death certificates in Canada (C), England and Wales (E), France (F) and Sweden (S). We also used a multiple cause approach. Age-standardized death rates (SDR) were calculated. RESULTS: The SDR for MI, HF or PE as the underlying cause of death, all decreased during the last decade. The decrease in SDR secondary to MI exceeded that for HF or PE. Concerning multiple cause of death, a greater decrease was also found for MI, compared with HF or PE. CONCLUSIONS: We confirm the beneficial trends in SDR with MI, HF or PE both as underlying or multiple causes in the studied countries. For HF and PE, multiple cause approach seems more accurate to describe the burden of these two pathologies. Our study also suggests that more efforts should be dedicated to HF and PE in order to achieve similar trends than in MI.

SEOM clinical guidelines for the treatment of small-cell lung cancer 2013.

In this updated SCLC guidelines the authors have reviewed the "SEOM recommendation" for diagnosis and treatment of patients, including consideration for elderly and unfit patients. We hope the SCLC guidelines will be useful for residents and oncology teams.

Prognostic implications of tissue oxygen saturation in human septic shock.

PURPOSE: To analyze the prognostic value of tissue oxygen saturation (StO(2)) in septic shock patients with restored mean arterial pressure (MAP). METHODS: This was a prospective observational study of patients admitted to the ICU in the early phase of septic shock, after restoration of MAP. Demographic data, severity score, hemodynamics, blood lactate, acid-base status, and StO(2) were measured at inclusion followed by a transient vascular occlusion test (VOT) to obtain the StO(2)-deoxygenation (DeOx) and StO(2)-reoxygenation (ReOx) rates. Sequential organ failure assessment (SOFA) score was measured at inclusion and after 24 h. RESULTS: Thirty-three patients were studied. StO(2) was 76 ± 10%, DeOx -12.2 ± 4.2%/min, and ReOx 3.02 ± 1.70%/s. MAP showed a significant correlation with VOT-derived slopes (r = -0.4, p = 0.04 for DeOx; and r = 0.55, p < 0.01 for ReOx). After 24 h, 17 patients (52%) had improved SOFA scores. Patients who did not improve their SOFA showed less negative DeOx values at inclusion. The association between DeOx and SOFA evolution was not affected by MAP. Both DeOx and ReOx impairment correlated with longer ICU stay (r = 0.44, p = 0.05; and r = -0.43, p = 0.05, respectively). CONCLUSIONS: In a population of septic shock patients with restored MAP, impaired DeOx was associated with no improvement in organ failures after 24 h. Decrements in DeOx and ReOx were associated with longer ICU stay. DeOx and ReOx were linked to MAP, and thus, their interpretation needs to be made relative to MAP.

Peripheral venous blood gases and pulse-oximetry in acute cardiogenic pulmonary oedema.

BACKGROUND: The role of venous blood gases as an alternative to arterial blood gases in patients with severe acute heart failure has not been established. OBJECTIVE: To assess the correlation between arterial and peripheral venous blood gases together with pulse-oximetry (SpO2), as well as to estimate arterial values from venous samples in the first hours upon admission of patients with acute cardiogenic pulmonary oedema. METHODS: Simultaneous venous and arterial blood samples were extracted on admission and over the next 1, 2, 3, 4, and 10 hours. SpO2 was also registered at the same intervals. RESULTS: A total of 178 pairs of samples were obtained from 34 consecutive patients with acute cardiogenic pulmonary oedema. Arterial and venous blood gases followed a parallel course in the first hours, showing high correlation rates at all time intervals. Venous samples underestimated pH (mean difference -0.028) and overestimated CO2 (+5.1 mmHg) and bicarbonate (+1 mEq/l). Conversely, SpO2 tended to underestimate SaO2 (mean±SD: 93.1±9.1 vs. 94.2±8.4). Applying simple mathematical formulae based on these differences, arterial values were empirically calculated from venous samples, showing acceptable agreement in the Bland-Altman test. Likewise, a venous pH <7.32, pCO2 >51.3 mmHg, and bicarbonate <22.8 mEq/l could fairly identify arterial acidosis, either respiratory or metabolic, with a test accuracy of 92, 68, and 91%, respectively. CONCLUSIONS: In patients with cardiogenic pulmonary oedema, arterial blood gas disturbances may be estimated from peripheral venous samples. By monitoring SpO2 simultaneously, arterial punctures could often be avoided.

[Objectives of hemodynamic resuscitation]. / Objetivos de la reanimación hemodinámica.

Cardiovascular failure or shock, of any etiology, is characterized by ineffective perfusion of body tissues, inducing derangements in the balance between oxygen delivery and consumption. Impairment in oxygen availability on the cellular level causes a shift to anaerobic metabolism, with an increase in lactate and hydrogen ion production that leads to lactic acidosis. The degree of hyperlactatemia and metabolic acidosis will be directly correlated to the development of organ failure and poor outcome of the individuals. The amount of oxygen available at the tissues will depend fundamentally on an adequate level of perfusion pressure and oxygen delivery. The optimization of these two physiologic parameters can re-establish the balance between oxygen delivery and consumption on the cellular level, thus, restoring the metabolism to its aerobic paths. Monitoring variables such as lactate and oxygen venous saturations (either central or mixed) during the initial resuscitation of shock will be helpful to determine whether tissue hypoxia is still present or not. Recently, some new technologies have been developed in order to evaluate local perfusion and microcirculation, such as gastric tonometry, near-infrared spectroscopy and videomicroscopy. Although monitoring these regional parameters has demonstrated its prognostic value, there is a lack of evidence regarding to its usefulness during the resuscitation process. In conclusion, hemodynamic resuscitation is still based on the rapid achievement of adequate levels of perfusion pressure, and then on the modification of oxygen delivery variables, in order to restore physiologic values of ScvO(2)/SvO(2) and resolve lactic acidosis and/or hyperlactatemia.

Non-invasive pressure support ventilation versus conventional oxygen therapy in acute cardiogenic pulmonary oedema: a randomised trial.

BACKGROUND: Non-invasive pressure support ventilation (NIPSV) is an effective treatment for acute respiratory failure in patients with chronic obstructive pulmonary disease. We assessed the efficacy of this therapy in acute cardiogenic pulmonary oedema in a randomised comparison with conventional oxygen therapy. METHODS: 40 patients were randomly assigned conventional oxygen therapy or NIPSV supplied by a standard ventilator through a face mask, with adjustment of tidal volume and pressure support in addition to a positive end-expiratory pressure of 5 cm water. Physiological measurements were obtained in the first 2 h and at 3 h, 4 h, and 10 h. The main endpoints were intubation rate and resolution time. Analyses were by intention to treat. FINDINGS: Three patients were withdrawn on the basis of clinical and chest radiography results. Endotracheal intubation was required in one (5%) of 19 patients assigned NIPSV and in six (33%) of 18 assigned conventional oxygen therapy (p=0.037). Resolution time (defined as a clinical improvement with oxygen saturation of 96% or more and respiratory rate less than 30 breaths/min) was significantly shorter in the NIPSV group (median 30 [IQR 15-53] vs 105 [50-230] min, p=0.002). NIPSV led to a rapid improvement in oxygenation in the first 2 h. There were no differences in hospital length of stay or mortality. INTERPRETATION: In this study of acute cardiogenic pulmonary oedema, NIPSV was superior to conventional oxygen therapy. Further studies should compare NIPSV with continuous positive airway pressure.

Diffuse pulmonary hemorrhage after fibrinolytic therapy for acute myocardial infarction.

We report a patient with diffuse pulmonary hemorrhage after streptokinase therapy for acute myocardial infarction. Hemoptysis, anemia, fever, jaundice, progressive bilateral pulmonary infiltrates and severe acute respiratory failure were observed. The patient required mechanical ventilation and recovered successfully. An immunological reaction to a highly antigenic agent such as streptokinase is considered in the pathogenesis of this complication.