Exploring management and outcomes of elderly patients with glioblastoma using data from two randomised trials (GEINO1401/EX-TEM).

PURPOSE: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. METHODS: Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. RESULTS: Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0-1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months. CONCLUSION: In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.

Individualised, perioperative open-lung ventilation strategy during one-lung ventilation (iPROVE-OLV): a multicentre, randomised, controlled clinical trial.

BACKGROUND: It is uncertain whether individualisation of the perioperative open-lung approach (OLA) to ventilation reduces postoperative pulmonary complications in patients undergoing lung resection. We compared a perioperative individualised OLA (iOLA) ventilation strategy with standard lung-protective ventilation in patients undergoing thoracic surgery with one-lung ventilation. METHODS: This multicentre, randomised controlled trial enrolled patients scheduled for open or video-assisted thoracic surgery using one-lung ventilation in 25 participating hospitals in Spain, Italy, Turkey, Egypt, and Ecuador. Eligible adult patients (age ≥18 years) were randomly assigned to receive iOLA or standard lung-protective ventilation. Eligible patients (stratified by centre) were randomly assigned online by local principal investigators, with an allocation ratio of 1:1. Treatment with iOLA included an alveolar recruitment manoeuvre to 40 cm H2O of end-inspiratory pressure followed by individualised positive end-expiratory pressure (PEEP) titrated to best respiratory system compliance, and individualised postoperative respiratory support with high-flow oxygen therapy. Participants allocated to standard lung-protective ventilation received combined intraoperative 4 cm H2O of PEEP and postoperative conventional oxygen therapy. The primary outcome was a composite of severe postoperative pulmonary complications within the first 7 postoperative days, including atelectasis requiring bronchoscopy, severe respiratory failure, contralateral pneumothorax, early extubation failure (rescue with continuous positive airway pressure, non-invasive ventilation, invasive mechanical ventilation, or reintubation), acute respiratory distress syndrome, pulmonary infection, bronchopleural fistula, and pleural empyema. Due to trial setting, data obtained in the operating and postoperative rooms for routine monitoring were not blinded. At 24 h, data were acquired by an investigator blinded to group allocation. All analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT03182062, and is complete. FINDINGS: Between Sept 11, 2018, and June 14, 2022, we enrolled 1380 patients, of whom 1308 eligible patients (670 [434 male, 233 female, and three with missing data] assigned to iOLA and 638 [395 male, 237 female, and six with missing data] to standard lung-protective ventilation) were included in the final analysis. The proportion of patients with the composite outcome of severe postoperative pulmonary complications within the first 7 postoperative days was lower in the iOLA group compared with the standard lung-protective ventilation group (40 [6%] vs 97 [15%], relative risk 0·39 [95% CI 0·28 to 0·56]), with an absolute risk difference of -9·23 (95% CI -12·55 to -5·92). Recruitment manoeuvre-related adverse events were reported in five patients. INTERPRETATION: Among patients subjected to lung resection under one-lung ventilation, iOLA was associated with a reduced risk of severe postoperative pulmonary complications when compared with conventional lung-protective ventilation. FUNDING: Instituto de Salud Carlos III and the European Regional Development Funds.

A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma.

PURPOSE: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. METHODS: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. RESULTS: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. CONCLUSION: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.

Usefulness of resuscitative endovascular balloon occlusion of the aorta (REBOA) in controlling puerperal bleeding in patients with abnormal placental implantation.

BACKGROUND AND AIMS: Abnormalities of placental implantation, which make up the spectrum of placenta accreta, are associated with high maternal morbidity and mortality due to massive bleeding during delivery. Placing aortic occlusion balloons helps control the bleeding, facilitating surgical intervention. A new device, resuscitative endovascular balloon occlusion of the aorta (REBOA), minimizes the risks and complications associated with the placement of traditional aortic balloons and is also efficacious in controlling bleeding. The aim of this study is to evaluate the usefulness, efficacy, and safety of REBOA in puerperal bleeding due to abnormalities of placental implantation. MATERIAL AND METHODS: Between November 2019 and November 2021, our interventional radiology team placed six REBOA devices in six women scheduled for cesarean section due to placenta accrete. RESULTS: Mean blood loss during cesarean section after REBOA (3507.5 mL) was similar to the amounts reported for other aortic balloons. The mean number of units of packed red blood cells required for transfusion was 3.5. Using REBOA provided the surgical team with adequate conditions to perform the surgery. There were no complications derived from REBOA, and the mean ICU stay was <2 days. CONCLUSION: The technical characteristics of the REBOA device make it a safe and useful alternative for controlling massive bleeding in patients with placenta accreta.

[Knowledge of chronic venous disease among healthcare professionals in Spain]. / Conocimiento de la enfermedad venosa crónica en los profesionales sanitarios en España.

INTRODUCTION: Chronic venous disease (CVD) is classified as the most prevalent vascular disease in humans. It has been associated with an increased incidence of cardiovascular diseases and is a strong predictor of all-cause mortality, representing a public health problem of the first magnitude. The objective of this study was to analyze the actions in the management of CVD in the daily clinical practice of health professionals in Spain. MATERIAL AND METHODS: Observational, descriptive and cross-sectional study with data collection through an opinion survey of 22 questions completed electronically through a Google® form for professionals involved in chronic venous disease care. Three hundred surveys were analyzed. The quantitative variables were represented with means and standard deviation and the qualitative ones with percentages and confidence intervals. RESULTS: Three hundred surveys analyzed. 65.3% were women. The most participatory age group was over 55 years of age. 85% of those surveyed considered that CVD is an underdiagnosed and undertreated disease, with an added negative impact in terms of follow-up during the Covid-19 pandemic, since 91.7% considered that it had not been adequate. 47% of the participants did not know the CEAP classification and 56.3% did not know the venous clinical severity scale (VCSS). 92.7% of physicians prescribed compression stockings and 74.7% phlebotonic drugs. Hidrosmine was the best known and most prescribed venoactive drug (51.7%). 73% of the doctors recognized that they did not use any algorithm or protocol for the diagnosis, treatment and monitoring of CVD in their usual clinical practice and 91% stated that they were not trained in their workplaces. 54.3% of the physicians believed that one of the main limitations that made follow-up of the disease difficult was the lack of coordination with the vascular surgeons. CONCLUSIONS: Updating and responding to the training needs of professionals regarding CVD is essential to guarantee quality care continuity in the care of our patients.

Influence of Early Life Factors, including breast milk Composition, on the Microbiome of Infants Born to Mothers with and without Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Herein we analysed the influence of early life factors, including breast milk composition, on the development of the intestinal microbiota of infants born to mothers with and without IBD. METHODS: The MECONIUM [Exploring MEChanisms Of disease traNsmission In Utero through the Microbiome] study is a prospective cohort study consisting of pregnant women with or without IBD and their infants. Longitudinal stool samples were collected from babies and analysed using 16s rRNA sequencing and faecal calprotectin. Breast milk proteomics was profiled using Olink inflammation panel. RESULTS: We analysed gut microbiota of 1034 faecal samples from 294 infants [80 born to mothers with and 214 to mothers without IBD]. Alpha diversity was driven by maternal IBD status and time point. The major influencers of the overall composition of the microbiota were mode of delivery, feeding, and maternal IBD status. Specific taxa were associated with these exposures, and maternal IBD was associated with a reduction in Bifidobacterium. In 312 breast milk samples [91 from mothers with IBD], mothers with IBD displayed lower abundance of proteins involved in immune regulation, such as thymic stromal lymphopoietin, interleukin-12 subunit beta, tumour necrosis factor-beta, and C-C motif chemokine 20, as compared with control mothers [adjusted p = 0.0016, 0.049, 0.049, and 0.049, respectively], with negative correlations with baby´s calprotectin, and microbiome at different time points. CONCLUSION: Maternal IBD diagnosis influences microbiota in their offspring during early life. The proteomic profile of breast milk of women with IBD differs from that of women without IBD, with distinct time-dependent associations with baby's gut microbiome and feacal calprotectin.

An Unexpected Cause of Acute Abdomen Late After Heart Transplantation-A Case Report.

Cytomegalovirus (CMV) infection is a frequent complication after a solid organ transplant, and in 86% of the cases, CMV disease occurred during the first 6 months after transplantation. Invasive CMV infections may be present as ulcerative infections of the upper gastrointestinal tract with esophagitis, gastritis, and ulcerations of the duodenum and the small bowel; however, CMV infections of the pancreatobiliary system, especially papillitis, are rarely observed. We present a case report of a man who underwent a heart transplant 6 years before, with a clinical picture of duodenitis and a simultaneous pseudotumor of major duodenal papilla who developed signs of acute abdomen caused by gastrointestinal CMV infection, successfully treated with medical therapy with valganciclovir. There is an urgent need for developments in CMV and solid organ transplantation to stratify the risk of late-onset CMV disease.

Electroanatomical mapping improves procedural outcomes of cryoballoon pulmonary vein isolation (the Achieve Plus study).

BACKGROUND: Validation of pulmonary vein (PV) isolation (PVI) using only the Achieve catheter following cryoballoon ablation (CBA) is imperfect since pulmonary vein potentials (PVP) can be recorded in only 50-85% of the veins and residual PVP are found in up to 4.3-7.6% of the isolated veins in remapping studies. OBJECTIVE: To study if addition of electroanatomical mapping to Achieve catheter-guided CBA is superior for PVI. METHODS: One hundred patients were randomized between Achieve catheter-guided CBA (control group; N = 50) and Achieve catheter-guided CBA with additional EnSite voltage maps performed pre- and post-CBA (Achieve Plus group; N = 50). Confirmation of PVI was done by circular mapping catheter (CMC) and EnSite mapping by a second blinded operator. RESULTS: Despite apparent PVI in all PVs after CBA, incomplete PVI was present in 0 out of 50 patients (0%) and 0 out of 204 PVs in the Achieve Plus group versus 6 patients out of 50 (12%; P = 0.012) and 6 out of 203 PVs (3%; P = 0.013) in the control group. All 6 non-isolated PVs could be successfully isolated by additional cryoapplications. Procedure time was longer in the Achieve Plus group (75.76 ± 21.65 vs 66.06 ± 16.83 min; P = 0.014) with equal fluoroscopy times (14.85 ± 6.41 vs 14.33 ± 8.55; P = 0.732). CONCLUSION: The addition of electroanatomical EnSite mapping to the Achieve catheter improves the PVI rate of CBA and could be considered for future use. Design and Results of the Achieve Plus study. The Achieve Plus study shows that the addition of electro-anatomical EnSite mapping to the Achieve catheter improves PVI rate of CBA and could be considered for future use. See text for further explanation. ABBREVIATIONS: CBA: cryoballoon ablation; PVI: pulmonary vein isolation.

Similar programmed death ligand 1 (PD-L1) expression profile in patients with mild COPD and lung cancer.

Programmed Death Ligand 1 (PD-L1) is crucial in regulating the immunological tolerance in non-small cell lung cancer (NSCLC). Alveolar macrophage (AM)-derived PD-L1 binds to its receptor, PD-1, on surveilling lymphocytes, leading to lymphocyte exhaustion. Increased PD-L1 expression is associated with cigarette smoke (CS)-exposure. However, the PD-L1 role in CS-associated lung diseases associated with NSCLC, such as chronic obstructive pulmonary disease (COPD), is still unclear. In two different cohorts of ever smokers with COPD or NSCLC, and ever and never smoker controls, we evaluated PD-L1 expression: (1) via cutting-edge digital spatial proteomic and transcriptomic profiling (Geomx) of formalin-fixed paraffin-embedded (FFPE) lung tissue sections (n = 19); and (2) via triple immunofluorescence staining of bronchoalveolar lavage (BAL) AMs (n = 83). PD-L1 mRNA expression was also quantified in BAL AMs exposed to CS extract. PD-L1 expression was increased in the bronchiolar wall, parenchyma, and vascular wall from mild-moderate (GOLD 1-2) COPD patients compared to severe-very severe (GOLD 3-4) COPD patients and controls. Within all the COPD patients, PD-L1 protein expression was associated with upregulation of genes involved in tumor progression and downregulation of oncosuppressive genes, and strongly directly correlated with the FEV1% predicted, indicating higher PD-L1 expression in the milder vs. more severe COPD stages. In bronchioles, PD-L1 levels were strongly directly correlated with the number of functionally active AMs. In BAL, we confirmed that AMs from patients with both GOLD 1-2 COPD and NSCLC had the highest and similar, PD-L1 expression levels versus all the other groups, independently from active cigarette smoking. Intriguingly, AMs from patients with more severe COPD had reduced AM PD-L1 expression compared to patients with mild COPD. Acute CS extract stimulation increased PD-L1 mRNA expression only in never-and not in ever-smoker AMs. Lungs from patients with mild COPD and NSCLC are characterized by a similar strong PD-L1 expression signature in bronchioles and functionally active AMs compared to patients with severe COPD and controls. Active smoking does not affect PD-L1 levels. These observations represent a new resource in understanding the innate immune mechanisms underlying the link between COPD and lung cancer onset and progression and pave the way to future studies focused on the mechanisms by which CS promotes tumorigenesis and COPD.

A carcinoid tumor of the middle ear masquerading as a glomus tympanicum presenting with temporal lobe hemorrhage in a 70-year-old woman: Case report and review of the literature.

BACKGROUND: Paragangliomas in the central nervous system account for 0.6% of all head and neck neoplasms, with glomus tympanicum being the most common middle ear tumor. Carcinoid tumors are neuroendocrine tumors, representing less than 1% of neuroendocrine neoplasms in the middle ear. Misdiagnoses have been reported in the literature regarding glomus and carcinoid tumors, however, none have been in the central nervous system or middle ear. CASE DESCRIPTION: A 70-year-old female with a history of left temporal lobe tumor underwent unsuccessful resection due to intraoperative bleeding at an outside institution. However, biopsy prior to aborting the case led to the diagnosis of paraganglioma. Eight years postoperatively, the patient presented at our institution with acute confusion, aphasia, and altered mental status. Imaging revealed a 4cm left temporal intraparenchymal hematoma at the known tumor site with concern for intracranial tumor extension. Surgical resection was performed and previous symptoms resolved. Final pathology revealed a Grade II atypical carcinoid tumor with an unusually high Ki-67 of 50%. CONCLUSIONS: Carcinoid tumors of the middle ear constitute a differential diagnosis for patients presenting with temporal lobe hemorrhage. A combination of immunohistochemical staining with electron microscopy can assist in differentiating the tumor types. This atypical presentation for a carcinoid tumor in the middle ear suggests the need to consider carcinoid as the diagnosis in patients with a middle ear tumor invading into the temporal lobe and causing hemorrhage. These tumors may demonstrate an unusually high Ki-67 rate, in which case they should be treated aggressively.

Effectiveness of the MULTIPAP Plus intervention in youngest-old patients with multimorbidity and polypharmacy aimed at improving prescribing practices in primary care: study protocol of a cluster randomized trial.

BACKGROUND: The progressive ageing of the population is leading to an increase in multimorbidity and polypharmacy, which in turn may increase the risk of hospitalization and mortality. The enhancement of care with information and communications technology (ICT) can facilitate the use of prescription evaluation tools and support system for decision-making (DSS) with the potential of optimizing the healthcare delivery process. OBJECTIVE: To assess the effectiveness and cost-effectiveness of the complex intervention MULTIPAP Plus, compared to usual care, in improving prescriptions for young-old patients (65-74 years old) with multimorbidity and polypharmacy in primary care. METHODS/DESIGN: This is a pragmatic cluster-randomized clinical trial with a follow-up of 18 months in health centres of the Spanish National Health System. Unit of randomization: family physician. Unit of analysis: patient. POPULATION: Patients aged 65-74 years with multimorbidity (≥ 3 chronic diseases) and polypharmacy (≥ 5 drugs) during the previous 3 months were included. SAMPLE SIZE: n = 1148 patients (574 per study arm). INTERVENTION: Complex intervention based on the ARIADNE principles with three components: (1) family physician (FP) training, (2) FP-patient interview, and (3) decision-making support system. OUTCOMES: The primary outcome is a composite endpoint of hospital admission or death during the observation period measured as a binary outcome, and the secondary outcomes are number of hospital admission, all-cause mortality, use of health services, quality of life (EQ-5D-5L), functionality (WHODAS), falls, hip fractures, prescriptions and adherence to treatment. Clinical and sociodemographic factors will be explanatory variables. STATISTICAL ANALYSIS: The main result is the difference in percentages in the final composite endpoint variable at 18 months, with its corresponding 95% CI. Adjustments by the main confounding and prognostic factors will be performed through a multilevel analysis. All analyses will be carried out in accordance to the intention-to-treat principle. DISCUSSION: It is important to prevent the cascade of negative health and health care impacts attributable to the multimorbidity-polypharmacy binomial. ICT-enhanced routine clinical practice could improve the prescription process in patient care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04147130 . Registered on 22 October 2019.

Correlation between femoral version and severity of hip dysplasia in patients with advanced osteoarthritis prior to total hip arthroplasty. / Correlación entre versión femoral y gravedad de displasia del desarrollo de cadera en pacientes con artrosis avanzada.

INTRODUCTION: Developmental dysplasia of the hip (DDH) is a condition which comprises a number of joint abnormalities, including modifications in femoral version and neck-shaft angle (CCD), as well as a probable progression to osteoarthritis in certain cases. The main objective of this research was to find a correlation between femoral version and severity of DDH in patients with advanced osteoarthritis prior to joint replacement, which has not been previously reported. A secondary aim was to describe the modification of CCD as the severity of DDH increases. MATERIALS AND METHOD: Patients over the age of 15 with dysplastic hips and severe osteoarthritis prior to total hip arthroplasty were assessed between March 2018 and February 2019. Cases with any previous hip surgery were excluded. Anteroposterior pelvis X rays and femoral computed tomography (CT) were performed; femoral version was measured in CT and CCD was evaluated both in X rays (2 observers: A and B) and CT (one observer: musculoskeletal radiologist). Severity of DDH was defined by observers A and B according to Crowe classification in X rays. Statistical analysis was performed on SPSS v.21. Shapiro-Wilk test was used to confirm a normal data distribution. Intraclass correlation coefficient (ICC) determined the level of agreement between observers A and B. Pearson test assessed the correlation between femoral version and Crowe classification (positive if >0.5). Student's t test evaluated the statistical significance, which was defined as P<0.05. RESULTS: One-year assessment; 42 patients (54 hips), 76% women. Mean age 52.7 years. 45 hips completed the imaging set, 9 hips were assessed only with X rays. 48%, 16%, 7% and 28% were classified as Crowe I, II, III and IV (100% interobserver agreement). Crowe classes were grouped as I, II/III and IV due to a low number of cases classified as II and III. Mean femoral version was 21.73°, 26.8° and 43.58°, respectively. ICC between observers A and B for CCD measured in X rays was 0.96. Mean CCD measured in X rays for each group (I, II/III and IV) was 148.11°, 147.7° and 147°, and in CT was 131.21°, 127.9° and 122.14°, respectively. A significant difference was found in femoral version between groups I and IV (P=0.0002) and II/III and IV (P=0.042). Pearson correlation between femoral version and severity of DDH was positive (r=0.52; P=0.0002). A significant difference between CCD measured in CT was found between groups I and IV (P=0.003). CONCLUSIONS: A significant increase in femoral version related to severity of DDH and a positive correlation between these 2features were found. Furthermore, a significant decrease in CCD between groups I and IV measured in CT was revealed. These findings would be helpful for preoperative planning of total hip replacement in osteoarthritis secondary to DDH, because once the surgeon has assessed the severity of DDH on X rays or CT, an increased femoral version could be expected. Therefore, availability of specific implants such as conic, modular or cemented stems is critical, in order to modify the femoral anteversion to normal values in the most severe cases.

Increased levels of soluble fms-like tyrosine kinase-1 are associated with adverse outcome in pregnant women with COVID-19.

OBJECTIVE: In addition to the lungs, the placenta and the endothelium can be affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are markers of endothelial dysfunction and could potentially serve as predictors of severe coronavirus disease 2019 (COVID-19). We aimed to investigate the association of serum concentrations of sFlt-1 and PlGF with the severity of COVID-19 in pregnancy. METHODS: This was a prospective cohort study carried out in a tertiary care hospital in Mexico City, Mexico. Symptomatic pregnant women with a positive reverse-transcription quantitative polymerase chain reaction test for SARS-CoV-2 infection who fulfilled the criteria for hospitalization were included. The primary outcome was severe pneumonia due to COVID-19. Secondary outcomes were intensive care unit (ICU) admission, viral sepsis and maternal death. sFlt-1 levels were expressed as multiples of the median (MoM). The association between sFlt-1 and each adverse outcome was explored by logistic regression analysis, adjusted for gestational age for outcomes occurring in more than five patients, and the predictive performance was assessed by receiver-operating-characteristics-curve analysis. RESULTS: Among 113 pregnant women with COVID-19, higher sFlt-1 MoM was associated with an increased probability of severe pneumonia (adjusted odds ratio (aOR), 1.817 (95% CI, 1.365-2.418)), ICU admission (aOR, 2.195 (95% CI, 1.582-3.047)), viral sepsis (aOR, 2.318 (95% CI, 1.407-3.820)) and maternal death (unadjusted OR, 5.504 (95% CI, 1.079-28.076)). At a 10% false-positive rate, sFlt-1 MoM had detection rates of 45.2%, 66.7%, 83.3% and 100% for severe COVID-19 pneumonia, ICU admission, viral sepsis and maternal death, respectively. PlGF values were similar between women with severe and those with non-severe COVID-19 pneumonia. CONCLUSION: sFlt-1 MoM is higher in pregnant women with severe COVID-19 and has the capability to predict serious adverse pregnancy events, such as severe pneumonia, ICU admission, viral sepsis and maternal death. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Benefica chirurgia. A global surgery project focusing on hernia surgery.

BACKGROUND: The aim of international health cooperation projects is to alleviate the deficiencies in the area of health in low resource settings. Hernia surgery is a procedure that is well suited to these missions, due to its low morbidity, the fact that it can be performed on an outpatient basis, and the improvement in quality of life that it provides. OBJECTIVE: To describe the results of Benefica Chirurgia (BC), a Spanish non-profit humanitarian association in hernia pathology. METHODS: Five one-week surgical campaigns were carried out in Ecuador between 2015 and 2019, involving anesthetists, general and pediatric surgeons. Surgical and medical equipment was provided and transported by BC. ASA I/II patients underwent surgery. RESULTS: Surgery was performed on 240 patients with hernia pathology on 27 days. Sixty-three per cent of patients were male and the mean age was 48.2 years (range: 1-83). Hernia location was inguinal in 113 patients, umbilical in 101, and other in 26. The anesthetic technique used was spinal in 185 patients (77.1%), local plus intravenous sedation in 31 (12.9%), and general in 24 (10%). The surgical technique used was hernioplasty in 191 patients, herniorrhaphy in 31, incisional hernia repair in 15 and herniotomy in three. Surgery was performed on an outpatient basis in 98.4% of cases. Morbidity was 2%. Long-term postoperative evaluation is very complex. CONCLUSION: These campaigns make a significant contribution to health in low resource settings and provide great personal satisfaction for those involved. Standards achieved in the immediate postoperative period were similar to those obtained at the surgeons' centers in Europe. However, it is difficult to establish the rates of recurrence and chronic pain.

Comprehensive management of risk factors in peripheral vascular disease. Expert consensus.

INTRODUCTION: There is currently a degree of divergence among the main clinical practice guidelines on the management of risk factors for peripheral arterial disease (PAD). This project aims to gain understanding of the management of PAD risk factors in clinical practice and to reach a multidisciplinary consensus on the strategies to be followed in order to optimize its identification, treatment, and follow-up. METHODOLOGY: A multidisciplinary consensus following the Delphi methodology. RESULTS: Professionals (n = 130) with extensive experience in PAD participated in this consultation. The results suggest that in order to optimize the control of risk factors, efforts should be aimed at: (1) promoting the involvement and awareness of all specialists in the identification of and screening for the disease; (2) guaranteeing the possibility of evaluating the ankle-brachial index (ABI) in all the medical specialties involved; (3) promoting strategies for patients to quit smoking through the use of drugs, programs, or referrals to specialized units; (4) promoting an appropriate Mediterranean-based diet and the prescription of daily exercise; (5) raising awareness of the importance of ensuring LDL cholesterol values below 70 mg/dL, especially in symptomatic but also in asymptomatic patients (<55 mg/dL following the publication of the ESC/EAS guide); (6) recommending the use of antiplatelet therapy in asymptomatic patients with diabetes mellitus (DM) and/or a pathological ABI; and (7) protocolizing the annual evaluation of ABI in high-risk patients. CONCLUSION: This document presents the 22 agreed-upon strategies which are intended to help professionals optimize multidisciplinary management of PAD risk factors.

Impact of Cadmium Mediated by Tobacco Use in Musculoskeletal Diseases.

Tobacco use has a negative impact on health due to its relationship with the development of high-mortality diseases, such as pulmonary cancer. However, the effect of cadmium (Cd), present in tobacco smoke, on the development of joint diseases has been scarcely studied. The objective of this review is to discuss the evidence regarding the mechanisms by which Cd exposure, through tobacco smoke, may lead to the development of osteoarthritis (OA), osteoporosis (OP), and rheumatoid arthritis (RA). There's evidence suggesting a string association between moderate to severe OA development and tobacco use, and that a higher blood concentration of Cd can trigger oxidative stress (OS) and inflammation, favoring cartilage loss. At the bone level, the Cd that is inhaled through tobacco smoke affects bone mineral density, resulting in OP mediated by a decrease in the antioxidant enzymes, which favors the bone resorption process. In RA, tobacco use promotes the citrullination process through Cd exposure and increases OS and inflammation. Understanding how tobacco use can increase the damage at the articular level mediated by a toxic metal, i.e., Cd, is important. Finally, we propose prevention, control, and treatment strategies for frequently disabling diseases, such as OA, OP, and RA to reduce its prevalence in the population.

A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial.

BACKGROUND: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. PATIENTS AND METHODS: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). RESULTS: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. CONCLUSIONS: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination.