Factors intervening in the childbirth experience: a mixed-methods study.

OBJECTIVE: To analyze the childbirth experience focusing on the intervening factors and on the delivery method. METHOD: A sequential and explanatory mixed-methods study guided by the World Health Organization document for positive childbirth experiences. The participants were puerperal women in a maternity teaching hospital from inland São Paulo (Brazil). The first quantitative stage involved descriptive analysis with Poisson regression of 265 answers to the "Termômetro da Iniciativa Hospital Amigo da Mulher e da Criança" ("Women- and Baby-Friendly Hospital Initiative Thermometer") questionnaire. The second stage, qualitative, thematically analyzed the interviews conducted with 44 puerperal women who took part in the first stage. Data integration was by connection. THE RESULTS AND DISCUSSION: The analysis by connection showed that among the factors that restricted the positive experience, C-section was predominant (61.9%), understood as an option due to fear of pain, the treatment modality and previous traumas. Restrictions referring to the presence of a companion (99.6%), not having privacy (83%), disrespectful situations (69.5%), too many touches (56.9%) and the absence of skin-to-skin contact (55%), among others, potentiated fear, loneliness, concern, shame, the perception of disrespect and insecurity with the assistance provided. The promoting factors were as follows: choosing the companion (95.4%) for collaborating in the safety perception, not having infections (83.9%), having continuous team monitoring (82.2%) and pain relief methods (78.9%), which were valued by the women. CONCLUSION: The intervening factors that promoted positive experiences were related to clinical and protocol-related issues and to service availability. The restrictive factors were associated with excess interventions, deprivation of rights and of choice, absence of privacy and restriction referring to the presence of a companion. Women with a normal postpartum period felt more insecure and disrespected when compared to those subjected to C-sections, whose choices were considered, although they had lower prevalence of skin-to-skin contact. There is an urgent need to apprehend women's experiences and turn them into actions that guarantee their lives in a safe and respectful way.

High frequency of non-susceptibility to ciprofloxacin in nontyphoid Salmonella recovered from Brazilian broiler chicken.

1. This study evaluated the minimal inhibitory concentration (MIC) of ciprofloxacin and the presence of plasmid-mediated quinolone resistance (PMQR) mechanisms in 97 nontyphoidal Salmonella spp. isolated from broilers and carcases from three different regions in Brazil. The presence of mutations in quinolone resistance determination regions (QRDRS) was investigated in the ciprofloxacin-resistant strain by DNA sequencing.2. Most of the Salmonella spp. (85.6%) had intermediate resistance to ciprofloxacin and only one isolate was resistant. MIC breakpoints ranged from ≤0.03 to 1 µg/ml and 67.0% of the strains had a MIC of 0.25 µg/ml (n=65). Thirteen strains (13.4%) were susceptible to ciprofloxacin with MIC ≤0.06 µg/ml. The qnrB gene was detected in eight isolates with intermediate resistance and in two susceptible strains. The other PMQR genes, qnrA, qnrC, qnrD, qnrS, qnrVC, aac(6')-Ib, qepA, oqxAB and mutations in QRDR were not detected in any strain.3. There was a high frequency of ciprofloxacin intermediate resistant Salmonella from broiler and broiler carcases from Brazil. The presence of these strains in poultry and derived products poses a risk to public health.

Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189.

BACKGROUND: In the phase III KEYNOTE-189 study (NCT02578680), pembrolizumab plus pemetrexed and platinum-based chemotherapy (pemetrexed-platinum) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC) versus placebo plus pemetrexed-platinum. We report updated efficacy outcomes from the protocol-specified final analysis, including outcomes in patients who crossed over to pembrolizumab from pemetrexed-platinum and in patients who completed 35 cycles (∼2 years) of pembrolizumab. PATIENTS AND METHODS: Eligible patients were randomized 2 : 1 to receive pembrolizumab 200 mg (n = 410) or placebo (n = 206) every 3 weeks (for up to 35 cycles, ∼2 years) plus four cycles of pemetrexed (500 mg/m2) and investigators' choice of cisplatin (75 mg/m2) or carboplatin (area under the curve 5 mg·min/ml) every 3 weeks, followed by pemetrexed until progression. Patients assigned to placebo plus pemetrexed-platinum could cross over to pembrolizumab upon progression if eligibility criteria were met. The primary endpoints were OS and PFS. RESULTS: After a median follow-up of 31.0 months, pembrolizumab plus pemetrexed-platinum continued to improve OS [hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.46-0.69] and PFS (HR, 0.49; 95% CI, 0.41-0.59) over placebo plus pemetrexed-platinum regardless of programmed death-ligand 1 expression. Objective response rate (ORR) (48.3% versus 19.9%) and time to second/subsequent tumor progression on next-line treatment (PFS2; HR, 0.50; 95% CI, 0.41-0.61) were improved in patients who received pembrolizumab plus pemetrexed-platinum. Eighty-four patients (40.8%) from the placebo plus pemetrexed-platinum group crossed over to pembrolizumab on-study. Grade 3-5 adverse events occurred in 72.1% of patients receiving pembrolizumab plus pemetrexed-platinum and 66.8% of patients receiving placebo plus pemetrexed-platinum. Fifty-six patients completed 35 cycles (∼2 years) of pembrolizumab; ORR was 85.7% and 53 (94.6%) were alive at data cut-off. CONCLUSIONS: Pembrolizumab plus pemetrexed-platinum continued to show improved efficacy outcomes compared with placebo plus pemetrexed-platinum, with manageable toxicity. These findings support first-line pembrolizumab plus pemetrexed-platinum in patients with previously untreated metastatic nonsquamous NSCLC.

Comparison of antimicrobial resistance in thermophilic Campylobacter strains isolated from conventional production and backyard poultry flocks.

1. The aim of this study was to compare the resistance pattern of thermophilic Campylobacter spp. isolated from conventional production (n = 34) and backyard poultry flocks (n = 36) from Rio de Janeiro State, Brazil. The disc diffusion method and statistical tests were used for investigation and analysis of the resistance pattern of Campylobacter spp. isolated from different rearing systems.2. Antimicrobial resistance percentages to amoxycillin with clavulanic acid (AMC), ampicillin (AMP), ceftiofur (CTF), ciprofloxacin (CIP), enrofloxacin (ENO), erythromycin (ERI), gentamicin (GEN) and tetracycline (TET) were 32.4%, 44.1%, 67.6%, 97.1%, 82.4%, 26.5%, 5.9% and 38.2% in conventional production flocks respectively, while the backyard flock's resistance levels were 0.0%, 13.9%, 69.4%, 100.0%, 91.7%, 5.6%, 0.0% and 16.7%, respectively.3. Campylobacter spp. from conventional poultry production was more resistant to AMC, AMO, ERI and TET (P > 0.05) when compared to strains from backyard poultry. A higher frequency of resistance to fluoroquinolones (FLQ), CIP and ENO, was observed in strains from both systems, demonstrating the spread of resistant strains among poultry production environments.

Cardiovascular disease and high blood pressure trend analyses from 2002 to 2016: after the implementation of a salt reduction strategy.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death around the world; however, many CVD events could be prevented if we focused on modification of the main risk factors. Increased salt consumption is estimated to have caused millions of deaths, mostly related to CVD, particularly stroke, which is the leading cause of death in Portugal. In our study, we aim to assess trends in the proportion of high blood pressure (HBP) in Acute Coronary Syndrome (ACS) patients as well as the trends in stroke and ACS in Portugal, especially after a set of public health initiatives were implemented to reduce salt intake. METHODS: The monthly proportion of ACS patients presenting with previously diagnosed HBP and the monthly rate of CVD admissions into public hospitals in Portugal were calculated. CVD rates were stratified into ACS rate and stroke rates. Data were stratified by demographics variables. An interrupted time-series model was used to assess changes over time. RESULTS: Breakpoint analysis revealed an estimated breakpoint around the year 2013 for the proportion of HBP patients, the following year there was a decreasing trend, however it was not significant. Analyses showed the trend before 2013 was increasing and started to decrease after this year. This decreased in proportion of HBP patients can be translated into a reduction of 555 people per year presenting with HBP in the ACS population. We analysed trends for ACS and stroke and tested the significance for a breakpoint in the year 2013. Although none of the remaining trends were significant for ACS crude rates and stroke crude rate, a decreasing trend was observed. CONCLUSIONS: This research provides an indication about the impact a population-wide approach to CVD risk factors has on CVD trends themselves. Our results suggest that population-wide approaches can have an impact on the prevention and improvement of CVD control, reducing the number of CVD events, and eventually reducing premature death by CVD. As more restrictions on salt intake are being planned in Portugal in the next years, it is highly relevant to assess what is the current panorama and what further reductions we can expect.

Multicenter, International Study of MIC/MEC Distributions for Definition of Epidemiological Cutoff Values for Sporothrix Species Identified by Molecular Methods.

Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrixschenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301 Sporothrix schenckii sensu stricto, 486 S. brasiliensis, 75 S. globosa, and 13 S. mexicana molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for S. schenckii and S. brasiliensis, respectively: amphotericin B, 4 and 4 µg/ml; itraconazole, 2 and 2 µg/ml; posaconazole, 2 and 2 µg/ml; and voriconazole, 64 and 32 µg/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 µg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for S. schenckii, as well as ECVs for S. globosa and S. mexicana These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.

Magnetic resonance correlation of iron content with neuromelanin in the substantia nigra of early-stage Parkinson's disease.

BACKGROUND AND PURPOSE: Magnetic resonance (MR) studies have demonstrated a significant reduction of neuromelanin in the substantia nigra (SN) of Parkinson's disease (PD) patients with high accuracy for differential diagnosis compared to non-PD controls and essential tremor. However, studies state that not knowing how paramagnetic effects of iron influence neuromelanin signal is a limitation. In this study a neuromelanin-sensitive MR sequence was combined with T2* relaxometry iron quantification analysis to study the SN of early-stage PD patients to investigate the correlation between these parameters. METHODS: The inclusion criteria were untreated de novo PD patients and a 2-5 year disease duration (early PD); in addition, age-matched controls were enrolled. These were studied at 3.0 T with a high-resolution T1-weighted MR sequence to visualize neuromelanin and a relaxometry sequence for iron quantification. The primary outcome was the correlation of the width of the neuromelanin high signal region and the T2* values in the lateral, central and medial segments of the SN. RESULTS: Very weak correlations of T2* values with neuromelanin width, positive for global and negative for the medial and lateral SN segments, were found in both PD groups and control subjects. The SN neuromelanin width was markedly reduced in the de novo and early PD groups compared with controls in all SN segments, but no significant difference in T2* values was found between the groups. CONCLUSIONS: The SN neuromelanin signal does not have a significant correlation with iron content in PD patients or controls. The neuromelanin MR signal reduction in PD does not seem to be significantly influenced by paramagnetic iron effects.

Adapted sport effect on postural control after spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: The aim of this study was to compare trunk muscle activation during anterior and lateral reach in athletic and sedentary individuals with spinal cord injury (SCI) and able-bodied people. SETTINGS: University Hospital-UNICAMP, Campinas, Brazil. METHODS: Individuals with complete traumatic SCI and thoracic neurological level were separated into two groups: sedentary (SSCI: n=10) and physically active (PASCI: n=10). The control group (C: n=10) without SCI was assessed. Trunk muscle activation was recorded during reach and grasp tasks. The significant level was set at P<0.05. RESULTS: The control group showed a highest mean activation for left longissimus muscle during all activities (P<0.05). The PASCI group presented significant highest activation for left iliocostalis muscles during all activities, except in the anterior reach task of 90% maximum reach (anterior reach (AR) 75: P=0.02; right lateral reach (RLR) 75: P=0.03; RLR90: P=0.01). The SSCI group presented highest activation for the left iliocostalis during the right lateral reach task of 75 and 90% maximum reach and right iliocostalis during the anterior reach task of 75% maximum reach (AR75: P=0.007; RLR75: P=0.02; RLR90: P=0.03). A different pattern of muscle activation between the control group and the groups with SCI was observed. CONCLUSION: Our results indicated that sports practice did not affect the trunk muscle activation in people with paraplegia. However, the pattern muscle activation in individuals with SCI is different compared with people without SCI during anterior reach tasks.

Subthalamic deep brain stimulation effects on odor identification in Parkinson's disease.

BACKGROUND AND PURPOSE: Olfactory dysfunction is common in Parkinson's disease (PD) and it is one of the earliest non-motor symptoms. A few studies have suggested that deep brain stimulation of the subthalamic nucleus (STN-DBS) could improve olfactory function. Our aim was to evaluate the acute effect of bilateral STN-DBS on a commonly used smell test in PD patients. METHODS: Fifteen PD patients who underwent bilateral STN-DBS and 15 controls were recruited. Patients and controls were tested for odor identification. RESULTS: No statistical differences were documented between ON and OFF STN-DBS acute stimulation concerning olfaction. Controls presented a better performance for olfactory identification than patients. CONCLUSIONS: Our exploratory study did not support that bilateral STN-DBS could have an acute effect on olfactory function in PD patients.

Substantia nigra neuromelanin magnetic resonance imaging in de novo Parkinson's disease patients.

BACKGROUND: Depigmentation of the substantia nigra (SN) and locus coeruleus (LC) is a conspicuous pathological feature of Parkinson's disease (PD) and is related to the loss of neuromelanin, whose paramagnetic properties result in high signal on specific T1-weighted magnetic resonance imaging (MRI). Recent studies have suggested that neuromelanin decrease in the SN and LC of PD patients may emerge as a possible diagnostic biomarker. The SN neuromelanin signal in de novo and early stage PD patients was studied to assess its diagnostic accuracy. This is the first study based on a semi-automated MRI analysis of the neuromelanin signal in de novo PD patients. METHODS: The inclusion criteria were untreated de novo PD and a 2-5 year disease duration; in addition, age matched healthy controls were enrolled. These were studied with a high-resolution T1-weighted MRI sequence at 3 T to visualize neuromelanin. The primary outcome was SN high signal area, length and neuromelanin/midbrain ratio obtained with semi-automated methods. RESULTS: A total of 12 de novo PD patients and 10 PD patients with a 2-5 year disease duration were evaluated. The area, length of the SN T1 high signal and the SN neuromelanin/midbrain ratio were markedly decreased in the PD groups compared with age-matched controls, with a substantial overlap between the two PD groups. CONCLUSIONS: Neuromelanin-sensitive MRI techniques can discriminate PD patients from healthy individuals with high sensitivity and specificity. Our findings are consistent with recent findings showing that PD neuromelanin changes remain stable during the course of the disease.

Status epilepticus-Therapeutic management at the pediatric emergency department.

INTRODUCTION: Status epilepticus is an important cause of pediatric neurological emergency. Immediate treatment is essential to prevent definitive neurological damage. Several antiepileptic drugs are available for the management of status epilepticus. METHODS: Retrospective study of patients admitted at the emergency department of a tertiary hospital for 5 years (2014-2019). We analyzed the compliance to the treatment guidelines for pediatric status epilepticus. RESULTS: One hundred and seventeen admissions were identified, 23.9% of these were febrile status epilepticus. Among the other cases, the most frequent cause was genetic (22.2%). The majority were convulsive status epilepticus (93.1%), 58.7% of which were generalized tonic-clonic seizures. Benzodiazepines were the most used first and second line drug (98.2% and 94.8%). The most frequent third drug used was diazepam (56.4%) followed by phenytoin (18.2%). An infra-therapeutic antiepileptic drug dose was given in 48.7% of cases. 49.6% presented with a prolonged status epilepticus and 6.8% needed intensive care. Incorrect sequence of drugs and infra-therapeutic doses were associated with prolonged status (p<0.001 and p<0.05) and an increased number of antiepileptic drugs used (p<0.001 and p<0.05). CONCLUSIONS: Benzodiazepines were the most frequently first and second line drugs used for status epilepticus management. Surprisingly, the most frequently third line drugs used were also benzodiazepines. These findings were partially explained by the misuse of infra-therapeutic doses of these drugs. Noncompliance with the implemented guidelines was associated with unfavorable outcomes.

Immune checkpoint blockers in solid organ transplant recipients and cancer: the INNOVATED cohort.

BACKGROUND: Patients with solid organ transplant (SOT) and solid tumors are usually excluded from clinical trials testing immune checkpoint blockers (ICB). As transplant rates are increasing, we aimed to evaluate ICB outcomes in this population, with a special focus on lung cancer. METHODS: We conducted a multicenter retrospective cohort study collecting real data of ICB use in patients with SOT and solid tumors. Clinical data and treatment outcomes were assessed by using retrospective medical chart reviews in every participating center. Study endpoints were: overall response rate (ORR), 6-month progression-free survival (PFS), and grade ≥3 immune-related adverse events. RESULTS: From August 2016 to October 2022, 31 patients with SOT (98% kidney) and solid tumors were identified (36.0% lung cancer, 19.4% melanoma, 13.0% genitourinary cancer, 6.5% gastrointestinal cancer). Programmed death-ligand 1 expression was positive in 29% of tumors. Median age was 61 years, 69% were males, and 71% received ICB as first-line treatment. In the whole cohort the ORR was 45.2%, with a 6-month PFS of 56.8%. In the lung cancer cohort, the ORR was 45.5%, with a 6-month PFS of 32.7%, and median overall survival of 4.6 months. The grade 3 immune-related adverse events rate leading to ICB discontinuation was 12.9%. Allograft rejection rate was 25.8%, and risk of rejection was similar regardless of the type of ICB strategy (monotherapy or combination, 28% versus 33%, P = 1.0) or response to ICB treatment. CONCLUSIONS: ICB could be considered a feasible option for SOT recipients with some advanced solid malignancies and no alternative therapeutic options. Due to the risk of allograft rejection, multidisciplinary teams should be involved before ICB therapy.

Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial.

BACKGROUND: In 2019, we reported the first efficacy and safety analysis of EUCROSS, a phase II trial investigating crizotinib in ROS1 fusion-positive lung cancer. At that time, overall survival (OS) was immature and the effect of crizotinib on intracranial disease control remained unclear. Here, we present the final analysis of OS, systemic and intracranial activity, and the impact of co-occurring aberrations. MATERIALS AND METHODS: EUCROSS was a prospective, single-arm, phase II trial. The primary endpoint was best overall response rate (ORR) using RECIST 1.1. Secondary and exploratory endpoints were progression-free survival (PFS), OS, and efficacy in pre-defined subgroups. RESULTS: Median OS of the intention-to-treat population (N = 34) was 54.8 months [95% confidence interval (CI) 20.3 months-not reached (NR); median follow-up 81.4 months] and median all-cause PFS of the response-evaluable population (N = 30) was 19.4 months (95% CI 10.1-32.2 months). Time on treatment was significantly correlated with OS (R = 0.82; P < 0.0001). Patients with co-occurring TP53 aberrations (28%) had a significantly shorter OS [hazard ratio (HR) 11; 95% CI 2.0-56.0; P = 0.006] and all-cause PFS (HR 4.2; 95% CI 1.2-15; P = 0.025). Patients with central nervous system (CNS) involvement at baseline (N = 6; 20%) had a numerically shorter median OS and all-cause PFS. Median intracranial PFS was 32.2 months (95% CI 23.7 months-NR) and the rate of isolated CNS progression was 24%. CONCLUSIONS: Our final analysis proves the efficacy of crizotinib in ROS1-positive lung cancer, but also highlights the devastating impact of TP53 mutations on survival and treatment efficacy. Additionally, our data show that CNS disease control is durable and the risk of CNS progression while on crizotinib treatment is low.

Short communication: Development and evaluation of predictive models of body weight for crossbred Holstein-Zebu dairy heifers.

Equations to predict body weight (BW) of crossbred Holstein-Zebu dairy heifers were developed and compared with current models (Heinrichs et al. for Holsteins, United States; Reis et al. for crossbred Holstein-Zebu, Brazil). The data set was constructed from 150 measurements of BW (320 ± 107 kg) and biometric measurements such as heart girth (HG, 161 ± 19.5 cm), withers height (WH, 126 ± 11.0 cm), and hip height (HH, 132 ± 11.3 cm) of heifers from 5 commercial dairy producers in the southern Amazon region in Brazil. The data were evaluated using mixed nonlinear models with herd as a random effect. Three nonlinear equations were fitted: BW (kg)=0.00058·HG (cm)(2.6135); BW (kg)=0.000618·HG (cm)(2.7362); and BW (kg)=0.000196·HH (2.8793). An independent database was constructed to evaluate the models from 38 treatment means of 4 feeding trials: BW 258 ± 54.3 kg, HG 142.5 ± 11.8 cm, WH 113.2 ± 6.0 cm, and HH 118.7 ± 9.1 cm (mean ± SD). The evaluations were based on the relationship between observed and predicted values of BW by linear regression, root mean square prediction error (RMSPE), and concordance correlation coefficient analysis. Only the proposed model using HG accurately predicted observed BW, with bias (observed - predicted) of 4.83 kg and RMSPE of 5.41% of observed BW (87.7% of random error). The models using WH and HH failed to accurately predict observed BW, with a bias of -3.06 and 72.02 kg, and RMSPE of 9.40% of observed BW (75.2% of random error and 23.1% of systematic error) and 30.81% of observed BW (81.2% of mean bias). Additionally, the models of Heinrichs and Reis used for comparison did not predict BW accurately, with a bias of 19.32 and 29.37 kg and RMSPE of 9.08% of observed BW (68.4% of mean bias and 31.4% of random error) and 12.58% of observed BW (81.9% of mean bias). The largest concordance correlation coefficient of the proposed HG-nonlinear model (0.930), compared with the models of Heinrichs and Reis of 0.845 and 0.708, confirmed the greater accuracy and precision of the new equation to predict BW in crossbred Holstein-Zebu dairy heifers.

Influence of different types of seat cushions on the static sitting posture in individuals with spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To evaluate the efficacy of the Postural Assessment Software PAS/SAPO in the posture analysis of individuals with spinal cord injury (SCI) during sitting position and to analyze if the use of different types of seat cushions-gel and foam, with no cushion-can interfere in the individual's posture during sitting position. SETTING: Centre of Rehabilitation at the University Hospital (FMRP-USP), Ribeirão Preto, Brazil. METHODS: Eight individuals, four paraplegics and four tetraplegics with SCI and 20 healthy individuals participated in the study. Photos were taken of individuals in the sitting position using foam, gel cushions and with no cushion. They were analyzed using the PAS/SAPO. The alignment of the anterior-superior iliac spine (ASIS) and the posterior pelvic tilt were evaluated from the angle formed between the ASIS and the greater trochanter of the femur. RESULTS: The group of healthy individuals presented the best postural alignment when compared with the group with SCI, both for the ASIS alignment (P<0.05) and for the degree of posterior pelvic tilt (P<0.05). No significant differences were found in the variables analyzed when the seat cushions were compared. CONCLUSION: The different types of cushions did not alter the sitting posture; however, individuals with SCI showed worse postural alignment than the healthy individuals. PAS/SAPO was demonstrated to be useful for postural assessment.

The EPICAL trial, a phase Ib study combining first line afatinib with anti-EGF vaccination in EGFR-mutant metastatic NSCLC.

INTRODUCTION: Combination of anti-EGFR monoclonal antibodies or immune checkpoint inhibitors with TKIs has shown minimal benefit in EGFR mutant (EGFR-mut) NSCLC patients. Consequently, new combination approaches are needed. PATIENTS AND METHODS: The EPICAL was a single arm, phase 1b study to evaluate safety, tolerability and anti-tumor activity of first line afatinib combined with anti-EGF vaccination in advanced EGFR-mut patients. EGFR status and mutations in liquid biopsies were determined by reverse transcriptase-polymerase chain reaction; serum biomarkers by ELISA and Western blotting analysis. RESULTS: The assay enrolled 23 patients, 21 completed the anti-EGF immunization phase. Treatment was well tolerated and no serious adverse events (SAEs) related to the anti-EGF vaccine were reported. Objective response and disease control rates were 78.3% (95%CI = 53.6-92.5) and 95.7% (95%CI = 78.1-99.9), respectively. After a median follow-up of 24.2 months, median progression-free survival (PFS) was 14.8 months (95% CI = 9.5-20.1) and median overall survival (OS) 26.9 months (95% CI = 23.0-30.8). Among the 21 patients completing the immunization phase, PFS was 17.5 months (95% CI = 12.0-23.0) and OS 26.9 months (95% CI = 24.6-NR). At the end of the immunization phase, all 21 patients showed high serum titers of anti-EGF antibodies, while EGF levels had decreased significantly. Finally, treatment with fully immunized patient's sera inhibited the EGFR pathway in tumor cells growing in vitro. CONCLUSIONS: Combination treatment with an anti-EGF vaccine is well tolerated; induces a sustained immunogenic effect and might enhance the clinical efficacy of EGFR TKIs.

Chicken feet bacteriological quality at 4 steps of technological processing.

The production of chicken feet is primarily intended for foreign markets, and there is still no specific legislation in Brazil that determines the quality standard of these products. The bacteriological quality of chicken feet was evaluated as a product for human consumption at different steps of the technological processes. Eighty broiler feet from 20 lots at 4 steps of processing were collected for quantitative analysis, total count of aerobic mesophilic bacteria, and determining the most probable number of coliforms and fecal coliforms. Thirty-eight pools of 15 broiler feet each from 19 lots were used for qualitative analysis and the isolation of Salmonella enterica spp. and Escherichia coli O157:H7. Escherichia coli O157:H7 was not found in any of the samples. Salmonella spp. were isolated in 68% (13/19) of the lots. The Salmonella Schwarzengrund serotype was found in 12 of the 13 lots of positive samples and the Salmonella Anatum and Salmonella Corvallis serotypes were identified in the remaining lot. Processing is effective in reducing contamination by mesophilic bacteria, coliforms, and Salmonella spp. in these products. This work constitutes the first study in Brazil on microbiological quality of chicken feet.

Risk and vulnerability assessment in coastal environments applied to heritage buildings in Havana (Cuba) and Cadiz (Spain).

In this paper, diagnostic tools are utilized to conduct a vulnerability analysis of monuments located in a coastal environment in accordance with a raft of standards drawn up by the International Organization for Standardization (ISO) 31000, in order to identify the main risks for Cultural Heritage in Havana (Cuba) and Cadiz (Spain). Vulnerability analysis is based on a Leopold matrix, which models the relationship between major hazards and pathologies in order to evaluate coastal influence and the risks for the conservation of cultural heritage. The quantitative matrix allows for a cause-effect analysis to be conducted for the main scenarios, related to the state of conservation. These relationships are a key step in risk assessment and treatment strategies. Major hazards have been identified by different public bodies and agencies to provide information about the probability and intensity of these variables in the vulnerability matrix. The combination of vulnerability index assessment, which depends on intrinsic variables and environmental scenarios, and knowledge of the main hazards in Havana and Cadiz, has provided useful tools to conduct risk assessments for cultural heritage conservation in coastal environments, where climate conditions, geomorphology and social issues are the main hazards, while vulnerability is associated with conservation plans. These tools provide information that will enable decision-makers in different coastal environments to prioritize strategies for cultural heritage preservation.