Prevalence and clinical implications of germline pathogenic variants in cancer predisposing genes in young patients across sarcoma subtypes.

BACKGROUND: Sarcomas are a rare and diverse group of cancers occurring mainly in young individuals for which an underlying germline genetic cause remains unclear in most cases. METHODS: Germline DNA from 177 children, adolescents and young adults with soft tissue or bone sarcomas was tested using multigene panels with 113 or 126 cancer predisposing genes (CPGs) to describe the prevalence of germline pathogenic/likely pathogenic variants (GPVs). Subsequent testing of a subset of tumours for loss of heterozygosity (LOH) evaluation was performed to investigate the clinical and molecular significance of these variants. RESULTS: GPVs were detected in 21.5% (38/177) of the patients (15.8% in children and 21.6% in adolescents and young adults), with dominant CPGs being altered in 15.2% overall. These variants were found in genes previously associated with the risk of developing sarcomas (TP53, RB1, NF1, EXT1/2) but also in genes where that risk is still emerging/limited (ERCC2, TSC2 and BRCA2) or unknown (PALB2, RAD50, FANCM and others). The detection rates of GPVs varied from 0% to 33% across sarcoma subtypes and GPV carriers were more likely to present more than one primary tumour than non-carriers (21.1%×6.5%; p=0.012). Loss of the wild-type allele was detected in 48% of tumours from GPV carriers, mostly in genes definitively associated with sarcoma risk. CONCLUSION: Our findings reveal that a high proportion of young patients with sarcomas presented a GPV in a CPG, underscoring the urgency of establishing appropriate genetic screening strategies for these individuals and their families.

Prepubertal to adulthood exposure to low doses of glyphosate-based herbicide increases the expression of the Havcr1 (Kim1) biomarker and causes mild kidney alterations.

Glyphosate is a nonselective and postemergent herbicide used to combat weeds in several crops, which raises concerns about risks to human health since residues are detected in urine, human milk, surface water and several types of food. Feces and urine are the major routes of elimination of glyphosate, making the kidney a sensitive target for the development of toxicity. In fact, farmers are at high risk of developing chronic kidney disease. In this sense, this study aims to investigate kidney function by measuring the serum levels of urea and creatinine, examining the histological morphology, and analyzing the mRNA expression of genes related to tubular transport of ions, urea and urates and the biomarker of kidney disease Kim1, and the levels of lead in the kidney in male Wistar rats orally exposed to low levels of glyphosate-based herbicide (GBH: 0, 0.5 or 5 mg/kg) from weaning to adult life by gavage. GBH0.5 showed reduced serum urea concentration, presence of tubulointerstitial swelling and mononuclear cell infiltration into the interstitium, increased gene expression of Kim1 and reduced gene expression of Slc14a1. GBH5 showed reduced serum urea and increased serum creatinine concentrations, tubulointerstitial swelling, interstitial fibrosis, and reduced expression of Trpm6 and Trpv5. Exposure to GBH did not affect the levels of Pb in the kidneys of animals. In conclusion, glyphosate at low doses may cause mild kidney damage. It is necessary to evaluate whether the long-term effects of this constant injury may contribute to the development of chronic kidney disease of uncertain etiology.

Effects of photobiomodulation therapy on the functional performance of healthy individuals: a systematic review with meta-analysis.

The aim of this study is to assess the effect of photobiomodulation therapy (PBMT) on functional performance concerning strength, fatigue, and functional capacity in healthy individuals. This systematic review with meta-analysis involved searches on data platforms and active searches of randomized clinical trials, focusing on PBMT as the sole intervention. Primary outcomes assessed included strength, fatigue, and functional capacity. Three reviewers screened studies by title and abstract using Rayyan, and data were extracted using a specific form. Bias risk was assessed using RoB2, and confidence in the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The RevMan was used for meta-analysis. Sixteen studies were included, totaling 340 individuals (183 males and 157 women). Most articles presented a low risk of bias. Variability was observed in device types and application domains, including wavelengths (655-905 nm), power (10-200 nW), energy (0.6-30 J per point), and time (30-100 s per point). PBMT improved fatigue recovery (mean difference: 5.87; 95% CI 3.83, 7.91). There was no enhancement in strength (peak torque: mean difference 12.40; 95% CI -5.55, 30.55; one-repetition maximum test: mean difference 39.97, 95% CI -2.44, 82.38; isometric and isokinetic strength: mean difference 2.77, 95% CI -14.90, 20.44) nor improvement in short-term (mean difference 0.67, 95% CI -0.58, 1.91) and long-term (mean difference 18.44, 95% CI -55.65, 92.54) functional capacity. PBMT may aid in favoring fatigue recovery in healthy individuals; however, there's no evidence to support PBMT enhancing strength or improving functional capacity.

Development, preliminary validation and reliability of the colourful 'My Feelings Form' self-report for young children.

BACKGROUND: Patient-reported outcome measures place the patient at the centre of his/her care. There are calls to introduce child-reported outcome measures to mental health services. We aimed to (a) develop an age-appropriate patient-reported outcome measure for children's mental health, and (b) validate this in a primary school and Child and Adolescent Mental Health Service (CAMHS). METHODS: A list of items to measure children's mental health was proposed (Draft 1) and revised to 14 items following focus group and user consultation (Draft 2). A colourful, cartoon and emoji version was created in consultation with children (Draft 3); a professional cartoon artist created the final 'My Feelings Form' (MFF), with usability feedback (Draft 4). The MFF was tested by 317 children aged 4-13 years from one mixed-gender primary school at two time points in 1 day, and 25 children aged 4-13 years from CAMHS. Results were analysed using test-retest reliability and exploratory factor analysis; a receiver operator characteristic curve was constructed. RESULTS: The CAMHS group scored significantly higher than the school group for the mean total score (23.5 ± 11.3 vs. 16.1 ± 6.2) and for 10 items. Test-retest reliability was acceptable (correlation = 0.74, p < .001). Exploratory factor analysis using 10 informative items identified two factors - emotional factor (Cronbach's alpha = 0.74) and function factor (Cronbach's alpha = 0.59). The revised 10-item form has a Cronbach's alpha of 0.77; a cut-off of 12 has a sensitivity of 80% and specificity of 60%, indicating that it correctly identified 80% of those who were attending CAMHS and gave 60% of the schoolchildren a negative result. CONCLUSIONS: The colourful MFF was co-produced with children, and preliminary data suggest that it is a useful patient-reported outcome measure for children's mental health.

Efficacy of a hypolipid diet in patients with primary antiphospholipid syndrome with dyslipidemia: a prospective study.

Although dyslipidemia is associated with poorer prognosis in antiphospholipid syndrome (APS), the management of lipid disorders can be challenging. While statins may increase the bleeding risk associated with anticoagulation, the effectiveness of hypolipid diet (HD) has not yet been established in patients with autoimmune disorders. In this study, we evaluated whether HD is associated with decreases in cholesterol levels in patients with thrombotic primary APS (t-PAPS) and dyslipidemia. Nutritional and lipid profiles were assessed before HD was initiated (baseline) and after 3 and 6 months with HD. A 24-h dietary recall was applied to assess the adherence to the diet. Forty-four patients were included, mean age was 43 years (± 12.93) and 65% were female. After HD was started, the intake of carbohydrates, lipids, saturated fats and cholesterol decreased, whereas dietary fiber intake increased. Levels of total cholesterol (TC) and non-high density lipoprotein cholesterol (non-HDL-C) decreased after 3 and 6 months of HD, as compared to baseline (P = 0.007 and P = 0.008). Low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) values did not change during the study period. The mean body mass index (BMI) decreased from 28.4 to 27.8 kg/m2 after six months of HD (p < 0.0001). In subgroup analysis, the effects of HD were more pronounced in patients with high TC, LDL-C or non-HDL-C levels at baseline and in those without obesity or hypertension. Nutritional intervention is feasible among t-PAPS and could be an alternative therapy to modulate lipid metabolism in this population.

Neutrophil activation and circulating neutrophil extracellular traps are increased in venous thromboembolism patients for at least one year after the clinical event.

Neutrophil activation and neutrophil extracellular traps (NETs) have been associated with the pathogenesis of venous thromboembolism (VTE). Considering VTE-associated chronic sequelae, which suggest that some pathological mechanisms remain after the acute episode, we investigated whether neutrophil activation is increased in patients with a prior VTE at least one year before this investigation. Thirty-seven patients with prior VTE and 37 individuals with no history of VTE were included. Neutrophil activity was evaluated by the expression of the adhesive molecule activation-specific epitopes LFA-1 (CD11a) and MAC-1 (CD11b), chemotaxis, reactive oxygen species (ROS) and by MPO-DNA complexes as markers of NETs. The adhesive molecules sICAM-1 and sVCAM-1, involved in the cross talk between neutrophil and endothelial cells, were also evaluated. Patient neutrophils presented increased CD11a expression before and after TNF-α stimulus, whereas increased CD11b expression was observed only after TNF-α stimulus, as compared to controls. Neutrophil chemotaxis on both, basal state and after IL-8 stimulus, on circulating levels of sICAM-1 and sVCAM-1, and on MPO-DNA complexes were also increased in VTE patients. ROS release was similar between patients and controls. This is, to our knowledge, the first study to investigate neutrophil inflammatory activity in VTE patients a long period after an acute event (approximately 2 years). The results showed altered neutrophil activation patterns in these patients. While activated neutrophils can cause endothelial activation and injury, the activated endothelium can induce the release of NETs with consequent endothelial cytotoxicity, creating a vicious cycle of activation between neutrophils and endothelium that can lead to thrombosis. VTE patients (approximately 2 years after the clinical event) present an altered neutrophil activation state evidenced by increased activity of the LFA-1 and Mac-1 adhesive molecules, as well as increased chemotaxis and circulating levels of NETs remnants. Circulating levels of ICAM-1 and VCAM-1, which are endothelial adhesive molecules, are also increased in VTE patients, suggesting not only an exacerbated endothelial activation and dysfunction, but also an interaction of the neutrophil adhesive molecules with their endothelial ligands, favoring the migration process of neutrophil.

Encapsulation of safflower oil in nanostructured lipid carriers for food application.

Safflower oil (SO) is mainly rich in linoleic acid (ω-6), oleic acid (ω-9), and other bioactives with potential antioxidant, antidiabetic, thermogenic, anti-inflammatory, cardioprotective and anticancer activities. The reduced aqueous solubility and high susceptibility to oxidative degradation are undesirable for food applications and can be overcome by incorporation in lipid nanoparticles. Thus, the main goal was to develop and characterize SO-loaded nanostructured lipid carriers (NLC-SO) and to evaluate their potential for protection of the antioxidant activity of the bioactive. NLC-SO showed average size of 222 ± 2.0 nm, zeta potential of  43 ± 3.5 mV and the encapsulation efficiency was 49.0 ± 2.8%, combined with high thermal compatibility (up to 228 °C) and physical stability for up to 60 days in aqueous dispersion. Besides, the NLC-SO showed threefold reduction in the DPPH radical scavenge activity after encapsulation, indicating protection of the antioxidant components of the SO and preservation of the bioactives. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05078-5.

Prognostic impact of platinum sensitivity in ovarian carcinoma patients with brain metastasis.

BACKGROUND: Brain metastasis (BM) is a rare event in ovarian cancer patients. The current prognostic scores that have been used for other tumors do not account for specific characteristics of ovarian cancer, such as platinum sensitivity. METHODS: This retrospective cohort study examined patients with ovarian carcinoma and BM who were treated at a single institution from January 2007 to December 2017. Clinical data on the diagnosis of BM and follow-up were collected. Cox regression was used to evaluate prognostic factors for overall survival (OS). RESULTS: Of 560 patients, 26 presented with BM. Eight patients were treated with surgery, 15 with whole-brain radiotherapy (RT), and 5 with stereotactic RT, and 4 patients received systemic treatment at the diagnosis of BM. The median OS was 10.8 months. The following factors were associated with OS: platinum-sensitive recurrence (HR 0.34, 95% CI 0.12-0.99; p = 0.049), higher number of previous treatment lines (HR 1.57, 95% CI 1.12-2.19; p = 0.008), ECOG performance status (HR 2.52, 95% CI 1.24-5.09; p = 0.010), and longer interval from initial diagnosis to BM (p = 0.025). Notably, the number of brain metastasis, the largest tumor size, and progression outside of the CNS were not related to survival. Platinum sensitivity was not associated with any of the classic prognostic factors in brain metastasis patients such as number or size of brain metastasis or disease progression outside the CNS strengthening the hypothesis of the importance of platinum sensitivity to the prognosis of ovarian cancer patients with BM. CONCLUSIONS: The factors related to the biological behavior of the ovarian cancer such as platinum sensitivity at the time of BM diagnosis, fewer number of previous treatment lines and interval from initial diagnosis were associated with survival in ovarian cancer patients with BM, while factors that are usually related to survival in BM in other cancers were not associated with survival in this cohort of ovarian cancer patients. The small number of patients did not allow us to exclude the prognostic role of these former factors that were not associated with survival in the present cohort.

Screening Veterans for Syphilis: Implementation of the Reverse Sequence Algorithm.

We evaluated the syphilis reverse sequence algorithm (RSA) in a Veteran Affairs facility, finding 5.5% reactive Treponema pallidum enzyme immunoassay (EIA) tests. In a subset of EIA+/VDRL-/TP-PA+ cases, 48% were previously treated. Of veterans with unknown/no prior therapy, only 45% had documentation of subsequent treatment, suggesting suboptimal interpretation of RSA results.

Effect of the injectable contraceptive depot-medroxyprogesterone acetate on coagulation parameters in new users.

AIM: The aim of this study was to assess the effects of the injectable depot-medroxyprogesterone acetate (DMPA) contraceptive on selected blood coagulation parameters in young, healthy new users. METHODS: The prospective study included 39 healthy women aged 20-39 years, with a body mass index (BMI; kg/m2 ) < 30, who were never users of DMPA, and who opted to use DMPA (21 women) or a copper intrauterine device (IUD; 18 women). The women in the two groups were matched for age (±1 year) and BMI (±1). Blood samples were obtained from all participants at baseline and at 6 and 12 months. Activated partial thromboplastin time, D-dimer, protein C, antithrombin, protein S, and thrombin generation test (lag time, endogenous thrombin potential, time to peak, and velocity index of thrombin generation) were analyzed. Repeated-measures analysis of variance was used to compare the groups. RESULTS: There were no significant differences between the groups at baseline with respect to any of the parameters evaluated; however, in the DMPA group, D-dimer levels were lower and the time to peak thrombin generation was longer than in the IUD group at 12 months of evaluation. CONCLUSION: Lower D-dimer and longer time to peak thrombin generation in new users of DMPA suggest a positive profile against hypercoagulability.

Polymeric Nanoparticles of Enoxaparin as a Delivery System: In Vivo Evaluation in Normal Rats and in a Venous Thrombosis Rat Model.

Enoxaparin is an anticoagulant widely used in the treatment and prophylaxis of deep vein thrombosis (DVT). The subcutaneous route of administration, sometimes in repeated doses during 24 hours, represents a limitation to its use. Thus, the development of a product that can be administered either subcutaneously, in a smaller number of applications becomes a major challenge, with interesting clinical applications. The use of a system for sustained release of drugs can help to meet that goal, by protecting and enabling a gradual released of the agent. This study consisted of the evaluation of in vivo anticoagulant and antithrombotic activity of biodegradable nanoparticles of poly (ε-caprolactone) (PCL) with enoxaparin after subcutaneous injection. The nanoparticles were prepared by the method of double emulsion (w/o/w) and solvent evaporation. Subcutaneous enoxaparin encapsulated in PCL nanoparticles (1000 IU/kg) showed a sustained release in vivo for up to 12 hours (Cmax 0.62 IU/mL) a significantly longer period (P < 0.01) when compared to free enoxaparin (1000 IU/Kg) that disappeared after 9 hours (Cmax 1.50 IU/mL), however with lower anti-Xa activity. The antithrombotic action of enoxaparin-nanoparticles was tested in a DVT model by stasis in rats. There were virtually no formation of venous thrombosis in any of the rats that received enoxaparin encapsulated in nanoparticles (0.03 mg), with a significant difference when compared to groups that received saline (17.2 mg, P < 0.001) and free enoxaparin (2.87 mg, P = 0.001). In summary, enoxaparin-encapsulated in polymeric nanoparticles showed a sustained release for a greater period than that of enoxaparin, and with excellent antithrombotic action. These results corroborate the promising use of pharmacological nanoparticles in clinical practice.

Widespread dissemination of CTX-M-15 genotype extended-spectrum-ß-lactamase-producing enterobacteriaceae among patients presenting to community hospitals in the southeastern United States.

Extended-spectrum-ß-lactamase (ESBL)-producing organisms are increasingly prevalent. We determined the characteristics of 66 consecutive ESBL-producing isolates from six community hospitals in North Carolina and Virginia from 2010 to 2012. Fifty-three (80%) ESBL-producing isolates contained CTX-M enzymes; CTX-M-15 was found in 68% of Escherichia coli and 73% of Klebsiella isolates. Sequence type 131 (ST131) was the commonest type of E. coli, accounting for 48% of CTX-M-15-producing and 66% of CTX-M-14-producing isolates. In conclusion, the CTX-M genotype and ST131 E. coli were common among ESBL isolates from U.S. community hospitals.

Endocannabinoid System Changes throughout Life: Implications and Therapeutic Potential for Autism, ADHD, and Alzheimer's Disease.

The endocannabinoid system has been linked to various physiological and pathological processes, because it plays a neuromodulator role in the central nervous system. In this sense, cannabinoids have been used off-label for neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHA), as well as in Alzheimer's disease (AD), a more prevalent neurodegenerative disease. Thus, this study aims, through a comprehensive literature review, to arrive at a better understanding of the impact of cannabinoids in the therapeutic treatment of patients with ASD, ADHD, and Alzheimer's disease (AD). Overall, cannabis products rich in CBD displayed a higher therapeutic potential for ASD children, while cannabis products rich in THC have been tested more for AD therapy. For ADHD, the clinical studies are incipient and inconclusive, but promising. In general, the main limitations of the clinical studies are the lack of standardization of the cannabis-based products consumed by the participants, a lack of scientific rigor, and the small number of participants.

Anodal tDCS over the motor cortex improves pain but not physical function in chronic chikungunya arthritis: Randomized controlled trial.

BACKGROUND: Chikungunya virus (CHIKV) is a globally prevalent pathogen, with outbreaks occurring in tropical regions. Chronic pain is the main symptom reported and is associated with decreased mobility and disability. Transcranial direct current stimulation (tDCS) is emerging as a new therapeutic tool for chronic arthralgia. OBJECTIVE: To evaluate the effectiveness of 10 consecutive sessions of anodal tDCS on pain (primary outcome) in participants with chronic CHIKV arthralgia. Secondary outcomes included functional status, quality of life, and mood. METHODS: In this randomized, double-blind, placebo-controlled trial, 30 participants with chronic CHIKV arthralgia were randomly assigned to receive either active (n = 15) or sham (n = 15) tDCS. The active group received 10 consecutive sessions of tDCS over M1 using the C3/Fp2 montage (2 mA for 20 min). Visual analog scale of pain (VAS), health assessment questionnaire (HAQ), short-form 36 health survey (SF-36), pain catastrophizing scale, Hamilton anxiety scale (HAS), timed up and go (TUG) test, lumbar dynamometry, 30-s arm curl and 2-min step test were assessed at baseline, day 10 and at 2 follow-up visits. RESULTS: There was a significant interaction between group and time on pain (p = 0.03; effect size 95 % CI 0.9 (-1.67 to -0.16), with a significant time interaction (p = 0.0001). There was no interaction between time and group for the 2-minute step test (p = 0.18), but the groups differed significantly at day 10 (p = 0.01), first follow-up (p = 0.01) and second follow-up (p = 0.03). HAQ and SF-36 improved but not significantly. There was no significant improvement in mental health, and physical tests. CONCLUSION: tDCS appears to be a promising intervention for reducing pain in participants with chronic CHIKV arthralgia, although further research is needed to confirm these findings and explore potential long-term benefits. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC): RBR-245rh7.

Matrix structure selection in the microparticles of essential oil oregano produced by spray dryer.

The goal of this work was to select the best combination of encapsulants for the microencapsulation of oregano essential oil by spray dryer with the addition of Arabic gum (AG), modified starch (MS) and maltodextrin (MA). The simplex-centroid method was used to obtain an optimal objective function with three variables. Analytical methods for carvacrol quantification, water activity, moisture content, wettability, solubility, encapsulation efficiency (ME) and oil retention (RT) were used to evaluate the best combination of encapsulants. The use of AG as a single wall material increased ME up to 93%. Carvacrol is the major phenolic compound existent in the oregano essential oil. Carvacrol exhibits a maximum concentration of 57.8% in the microparticle with the use of 62.5% AG and 37.5% MA. A greater RT (77.39%) was obtained when 74.5% AG; MS 12.7% and 12.7% MA were applied, and ME (93%) was improved with 100% of gum.

Total Healing of a Partial Rupture of the Supraspinatus Tendon Using Barbotage Technique Associated with Platelet-Rich Plasma: A Randomized, Controlled, and Double-Blind Clinical Trial.

The prevalence of partial rotator cuff tears (PRCTs) is high in the general population. Our hypothesis is that barbotage, when associated with platelet-rich plasma (PRP), is an effective method for healing these tears. The aim of this study was to compare the effects of barbotage with or without PRP on the healing of partial supraspinatus tendon tears (PSTTs). This study assessed the Western Ontario Rotator Cuff Index score and ultrasound (US) images at 6 weeks and 6 months after treatment. Patients in both groups showed clinical improvement, with no significant difference in scores at 6 weeks. However, at 6 months, the PRP group exhibited significant improvement (p = 0.019). Both groups experienced a reduction in ST tear size, but the PRP group demonstrated a significant enhancement at 6 weeks and 6 months. In conclusion, the US-guided barbotage technique, whether associated with PRP or saline solution, proved to be an effective treatment for clinical improvement and reduction in the size of PSTT. Better clinical improvement results were observed with PRP at 6 months. The combination of PRP with barbotage was superior in reducing the size of the ST tear at both 6 weeks and 6 months, resulting in complete healing in 79.3% of the tears.

Incidence of Abnormalities of the Gastric Tube Following Sleeve Gastrectomy and Its Role on Esophagitis Progression.

PURPOSE: The purpose of this study is to determine the incidence of gastric tube abnormalities after SG and its relationship with esophagitis progression. METHODS: Retrospective study which included 459 patients in the postoperative period of SG who underwent an esophagogastroduodenoscopy in both pre- and postoperative periods. The main studied variables were presence of gastric tube abnormalities (dilation, neofundus, twist, and hiatal hernia) and esophagitis progression. RESULTS: Among the 459 patients who underwent SG, 393 (85.6%) were women, and 66 (14.4%) men, with mean age of 40.4 years. Mean preoperative BMI was 39.70 kg/m2. In total, 20.3% of the sample presented progression of esophagitis after surgery. Among the whole sample, 130 (28.3%) presented with an abnormality of the remnant gastric tube. The most common alteration was gastric dilation, which occurred in 16.1% of the patients, followed by gastric twist (10.7%), neofundus (7.4%), and hiatal hernia (0.2%). Patients who presented with any abnormality of the gastric tube were significantly prone to presenting esophagitis progression (p = 0.013). When analyzing each morphological abnormality isolated, there was no statistically significant correlation. CONCLUSION: Abnormalities of the gastric tube are not uncommon after SG and seems to contribute partially to the relevant rates of GERD and esophagitis after this surgery.

Thrombosis Occurrence in COVID-19 Compared With Other Infectious Causes of ARDS: A Contemporary Cohort.

Thrombosis occurrence in coronavirus disease 2019 (COVID-19) has been mostly compared to historical cohorts of patients with other respiratory infections. We retrospectively evaluated the thrombotic events that occurred in a contemporary cohort of patients hospitalized between March and July 2020 for acute respiratory distress syndrome (ARDS) according to the Berlin Definition and compared those with positive and negative real-time polymerase chain reaction results for wild-type severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) using descriptive analysis. The association between COVID-19 and thrombotic risk was evaluated using logistic regression. 264 COVID-19-positive (56.8% male, 59.0 years [IQR 48.6-69.7], Padua score on admission 3.0 [2.0-3.0]) and 88 COVID-19-negative patients (58.0% male, 63.7 years [51.2-73.5], Padua score 3.0 [2.0-5.0]) were included. 10.2% of non-COVID-19 and 8.7% of COVID-19 patients presented ≥ 1 clinically relevant thrombotic event confirmed by imaging exam. After adjustment for sex, Padua score, intensive care unit stay, thromboprophylaxis, and hospitalization length, the odds ratio for thrombosis in COVID-19 was 0.69 (95% CI, 0.30-1.64). We, therefore, conclude that infection-induced ARDS carries an inherent thrombotic risk, which was comparable between patients with COVID-19 and other respiratory infections in our contemporary cohort.

Management of patients with recurrent/metastatic endometrial cancer: Consensus recommendations from an expert panel from Brazil.

Background: Endometrial cancer is of increasing concern in several countries, including Brazil, in part because of an ageing population, declines in fertility, and the increasing prevalence of obesity. Although endometrial tumors had lagged behind other cancer types in terms of treatment improvements, molecular characterization of these tumors is paving the way for novel therapies and an expansion of the therapeutic arsenal. We aimed to help medical oncologists who manage patients with recurrent or metastatic endometrial cancer in the Brazilian healthcare setting. Methods: The panel, composed of 20 medical oncologists, convened in November 2021 to address 50 multiple-choice questions on molecular testing and treatment choices. We classified the level of agreement among panelists as (1) consensus (≥75% choosing the same answer), (2) majority vote (50% to <75%), or (3) less than majority vote (<50%). Results: Consensus was present for 25 of the 50 questions, whereas majority vote was present for an additional 23 questions. Key recommendations include molecular testing for every patient with recurrent/metastatic endometrial cancer; choice of first-line treatment according to microsatellite instability and HER2, with the addition of programmed death ligand 1 (PD-L1) and hormone receptors (HRs) for second-line therapy; carboplatin and paclitaxel as the preferred option in first-line treatment of HER2-negative disease, with the addition of trastuzumab in HER2-positive disease; pembrolizumab plus lenvatinib as a key option in second line, regardless of HER2, PD-L1 or HRs; and various recommendations regarding treatment choice for patients with distinct comorbidities. Conclusion: Despite the existing gaps in the current literature, the vast majority of issues addressed by the panel provided a level of agreement sufficient to inform clinical practice in Brazil and in other countries with similar healthcare environments.