Phase I/IIa study of cetuximab with gemcitabine plus carboplatin in patients with chemotherapy-naive advanced non-small-cell lung cancer.

PURPOSE: This multicenter, open-label, phase I/IIa study was undertaken to establish the safety/toxicity profile of cetuximab in combination with gemcitabine and carboplatin in patients with chemotherapy-na?ve, epidermal growth factor receptor-positive, stage IV non-small-cell lung cancer. Secondary objectives were to gather preliminary evidence of efficacy including tumor response rate, time to progression, and overall survival. PATIENTS AND METHODS: Thirty-five patients received a total of 264 3-week cycles of treatment with cetuximab, carboplatin, and gemcitabine. An initial dose of cetuximab 400 mg/m2 intravenously was administered the first week, followed by weekly doses of 250 mg/m2. Carboplatin (area under the curve = 5, day 1) and gemcitabine 1,000 mg/m2 on days 1 and 8 were administered every 3 weeks. Patients were evaluated for tumor response after every two cycles of therapy. RESULTS: The most frequently reported adverse events related to cetuximab included an acne-like rash (88.6%), dry skin (34.3%), asthenia and skin disorders (31.4%), mucositis/stomatitis (25.7%), fever/chills (20%), and nausea/vomiting (17.1%). The majority of these toxicities were mild to moderate. One patient withdrew from the study because of a grade 3 allergic reaction. Myelosuppression was the most frequently observed toxicity related to chemotherapy. Responses among 35 assessable patients included 10 partial responses (28.6%). Twenty-one patients had stable disease. The median time to progression was 165 days, and the median overall survival was 310 days. CONCLUSION: The combination of cetuximab, carboplatin, and gemcitabine was well tolerated with an acceptable toxicity profile. Most grade 3 adverse events were attributable to chemotherapy. The response rate and median survival are encouraging and warrant additional investigation.     

Antibacterial activity and inhibition against Staphylococcus aureus NorA efflux pump by ferulic acid and its esterified derivatives

Objective: To evaluate the inhibitory activity of ferulic acid and four of its esterified derivatives (methyl, ethyl, propyl, and butyl) against resistance mech...     

Short-Term Pilot Study to Evaluate the Impact of Salbi Educa Nutrition App in Macronutrients Intake and Adherence to the Mediterranean Diet: Randomized Controlled Trial

Promoting a healthy diet is a relevant strategy for preventing non-communicable diseases. This study aims to evaluate the impact of an innovative tool, the SAlBi educa nutrition app, in primary healthcare dietary counseling to improve dietary profiles as well as adherence to the Mediterranean diet. A multi-center randomized control trial comprising 104 participants was performed. Both control (n = 49) and intervention (n = 55) groups attended four once-weekly sessions focusing on healthy eating habits and physical activity, over one month. As well as attending the meetings, the intervention group used the app, which provides self-monitoring and tailored dietary advice based on the Mediterranean diet model. In a second intervention (one arm trial), the potential of SAlBi educa was evaluated for three months during the COVID-19 pandemic. At 4 weeks, the intervention group had significantly increased their carbohydrate intake (7.7% (95% CI: 0.16 to 15.2)) and decreased their total fat intake (−5.7% (95% CI: −10.4 to −1.15)) compared to the control group. Significant differences were also found for carbohydrates (3.5% (95% CI: −1.0 to 5.8)), total fats (−5.9% (95% CI: −8.9 to −3.0)), fruits and vegetables (266.3 g/day (95% CI: 130.0 to 402.6)), legumes (7.7g/day (95% CI: 0.2 to 15.1)), starchy foods (36.4 g/day (95% CI: 1.1 to 71.7)), red meat (−17.5 g/day (95% CI: −34.0 to −1.1)), and processed meat (−6.6 g/day (95% CI: −13.1 to −0.1)) intakes during the COVID-19 pandemic. SAlBi educa is a useful tool to support nutrition counseling in primary healthcare, including in special situations such as the COVID-19 pandemic. Trial registration: ISRCTN57186362.     

Differences between Four Skinfold Calipers in the Assessment of Adipose Tissue in Young Adult Healthy Population

Background: The aim of this study was to analyze the validity of four different skinfold calipers, as well as to establish the differences between them in a healthy young adult population. Methods: The present study followed a cross-sectional design, including 138 participants, with 69 males (21.46 ± 2.52 years) and 69 females (22.19 ± 2.85 years). The measurement protocol included basic measurements of body mass and stretch stature and eight skinfolds with a Harpenden, Holtain, Slim Guide, and Lipowise. The ∑6 and ∑8 skinfolds and fat mass were calculated. The order in which the skinfold calipers were used was randomized. Results: No significant differences were found in either the Σ6 and Σ8 skinfolds or masses and fat percentages calculated with the skinfolds obtained with the different calipers (p > 0.05), and the inclusion of the covariates of sex, BMI, and hydration status of the participants showed no effect on the differences. The Bland–Altman test showed significant differences between the calipers (p < 0.001). Conclusion: It has been observed that the analyzed calipers have shown validity for the assessment of adiposity-related variables in a male and female sample of non-overweight, young healthy adults, but they are not interchangeable with each other when the assessment is meant to be compared over time or with other samples.     

Prevalence of Chikungunya,Dengue and Zika viruses in blood donors: a systematic literature review and meta-analysis

BackgroundBlood transfusion centres should understand the epidemiology of emerging diseases that are transmissible through the transfusion of blood components. The risk of transmission of arboviruses through this route has become apparent in recent years. The aim of our study is to summarise the reported prevalence (viraemic rate, seroprevalence and/or antigen detection) of Chikungunya (CHIKV), Dengue (DENV) and Zika (ZIKV) viruses in blood donors according to screening test used and world region.Materials and methodsWe conducted a systematic literature review and meta-analysis having searched for information in the main bibliographic databases (MEDLINE, Embase, and Scopus). The prevalence for each of the viruses was calculated according to the screening test used and geographic location.ResultsWe included 18 records on CHIKV, 71 on DENV, and 27 on ZIKV. The highest prevalences of RNA for CHIKV were 1.9% in Puerto Rico (2014), 1.0% in Thailand (2009), and 1.0% in French Polynesia (2014–15). The highest prevalences of RNA for DENV were 5.5% in Saudi Arabia (2015–16), 2.3% in Madeira, Portugal (2012–13), and 0.6% in Brazil (2012). The highest prevalences of RNA for ZIKV were 2.8% in French Polynesia (2013–14), 2.7% in Brazil (2015–16), and 1.8% in Martinique (2016). Overall seroprevalence, as assessed by IgG antibodies, was 21.6% for CHIKV, 24.0% for DENV, and 5.1% for ZIKV.DiscussionOur study shows a high proportion of donors who are viraemic and asymptomatic, especially during outbreaks, with prevalences surpassing 5% for DENV, 1% for CHIKV, and 2% for ZIKV. These data confirm a clear threat to blood transfusion safety. The elevated seroprevalence for these three arboviruses is also indicative of their wide circulation in populations, correlating with an increased risk of infected but asymptomatic donors. Health centres and institutions must address this threat, especially in tropical regions where the biggest outbreaks occur.     

Improvement of digestive symptoms in fibromyalgia patients following a diet modification according to histamine release test – an observational study

IntroductionThere is growing interest in the relationship between fibromyalgia and processes related to food, such as food intolerances. In fact, different associations have been described between the control of dietary habits and the improvement of the different symptoms of fibromyalgia.Material and methodsWe collected the results of applying a specific test of histamine release related to the diet of patients with fibromyalgia, and evaluated the changes in terms of the symptoms usually described by the patients. A total of 84 patients who met the established criteria were recruited; 40 of them underwent the exclusion diet for a period of 6 months, while the remaining ones continued with their usual dietary habits. All patients were instructed not to modify any other parameter during the study, such as medication, exercise, or other complementary treatments. The parameters studied were as follows: the Fibromyalgia Impact Questionnaire (FIQ), the Gastrointestinal Symptoms Rating Scale (GSRS), the pain Visual Analogue Scale (VAS), as well as the patients’ body weight was controlled.ResultsThere was a significant improvement (p < 0.05) in the group of patients who underwent the exclusion diet in assesment by GSRS and in total in total body weight. There were no differences compared to the rest of the patients in terms of VAS and FIQ.ConclusionsDiet modification in patients with fibromyalgia by specific histamine relase test improves certain clinical parameters related to the symptoms of the digestive sphere, compared to the control group. Our work opens a possible way of non-pharmacological treatment to improve some symptoms of this very prevalent disease.     

Targeted Mutations in the Fusion Peptide Region of La Crosse Virus Attenuate Neuroinvasion and Confer Protection against Encephalitis

La Crosse virus (LACV) is a major cause of pediatric encephalitis and aseptic meningitis in the Midwestern, Mid-Atlantic, and Southern United States, where it is an emerging pathogen. The LACV Gc glycoprotein plays a critical role in the neuropathogenesis of LACV encephalitis as the putative virus attachment protein. Previously, we identified and experimentally confirmed the location of the LACV fusion peptide within Gc and generated a panel of recombinant LACVs (rLACVs) containing mutations in the fusion peptide as well as the wild-type sequence. These rLACVs retained their ability to cause neuronal death in a primary embryonic rat neuronal culture system, despite decreased replication and fusion phenotypes. To test the role of the fusion peptide in vivo, we tested rLACVs in an age-dependent murine model of LACV encephalitis. When inoculated directly into the CNS of young adult mice (P28), the rLACV fusion peptide mutants were as neurovirulent as the rLACV engineered with a wild-type sequence, confirming the results obtained in tissue culture. In contrast, the fusion peptide mutant rLACVs were less neuroinvasive when suckling (P3) or weanling (P21) mice were inoculated peripherally, demonstrating that the LACV fusion peptide is a determinant of neuroinvasion, but not of neurovirulence. In a challenge experiment, we found that peripheral challenge of weanling (P21) mice with fusion peptide mutant rLACVs protected from a subsequent WT-LACV challenge, suggesting that mutations in the fusion peptide are an attractive target for generating live-attenuated virus vaccines. Importantly, the high degree of conservation of the fusion peptide amongst the Bunyavirales and, structurally, other arboviruses suggests that these findings are broadly applicable to viruses that use a class II fusion mechanism and cause neurologic disease.     

Valoración ecográfica del endometrio en pacientes tratadas con tamoxifeno

Objective

To measure endometrial thickness and characterize ultrasonographic endometrial images induced by tamoxifen, as well as to determine changes in ultrasonographic patterns throughout treatment.

Patients and methods

We analyzed 278 patients with breast cancer between 1995 and 2000 under adjuvant therapy with tamoxifen for 5 years. Annual ultrasonographic examination was performed. Endometrial thickness and the morphological endometrial patterns in stored ultrasonographic images were retrospectively analyzed.

Results

Endometrial thickness significantly increased during treatment from a mean of 7.84 mm in the first year to 16.67 mm in the fifth year. Five endometrial patterns were found on ultrasonography in patients receiving tamoxifen: linear, heterogeneous-hyperechoic, homogeneoushyperechoic, endometrial polyp, and suspicious for malignancy. The homogeneous-hyperechoic pattern predominated in the first year and the heterogeneous-hyperechoic pattern in the fifth year.

Conclusions

Tamoxifen increases endometrial thickness in the course of treatment and induces five ultrasonographic patterns which change year-by-year.