Effect of intravelar veloplasty on nasality in patients with velopharyngeal insufficiency

OBJETIVO: verificar o efeito da palatoplastia secundária realizada com veloplastia intravelar sobre a nasalidade e nasalância dos pacientes com fissura de palato reparada e insuficiência velofaríngea (IVF) e comparar os resultados entre estes pacientes, de acordo com o grau de fechamento velofaríngeo aferido na nasofaringoscopia. MÉTODO: estudo prospectivo com 40 pacientes de ambos os sexos, com idades entre 4 e 48 anos, com fissura de palato reparada e IVF residual, avaliado 3 dias antes e 8 meses após a palatoplastia, em média, divididos em dois grupos: um com 25 pacientes com falhas pequenas (grupo I) e outro com 15 pacientes com falhas médias a grandes (grupo II) no fechamento velofaríngeo. A hipernasalidade foi avaliada perceptivamente e nasalância foi avaliada por meio da nasometria. Diferenças entre grupos e etapas foram consideradas significativas ao nível de 5%. O estudo foi aprovado pelo Comitê de Ética para Pesquisa com Seres Humanos da Instituição. RESULTADOS: após a cirurgia, verificou-se redução da hipernasalidade em 84% dos pacientes do grupo I e em 73% dos pacientes do grupo II. Redução da nasalância foi observada em 52% dos casos do grupo I e em 43% dos pacientes do grupo II. CONCLUSÃO: a palatoplastia secundária com veloplastia intravelar levou à melhora da nasalidade na maioria dos pacientes analisados. Os resultados também demonstraram que a cirurgia foi mais efetiva nos pacientes que apresentavam falhas pequenas no fechamento velofaríngeo.PURPOSE: to check the effect of secondary palatoplasty performed with intravelar veloplasty on the nasality and nasalance of patients with repaired cleft palate and velopharyngeal insufficiency (VPI) and compare the outcome among these patients, according to the degree of velopharyngeal closure as analyzed by nasopharyngoscopy. METHOD: prospective study with 40 patients of both genders, aged from 4 to 48 years, with repaired cleft palate and residual VPI, evaluated for 3 days before and 8 months after palatoplasty, on average, divided into two groups: one with 25 patients with minor defect (group I) and the other with 15 patients with medium to large defect (group II) in velopharyngeal closure. Hypernasality was evaluated perceptually and nasalance was assessed by nasometry. Differences between groups and stages were considered to be significant at the 5% level. The local Ethics Committee for Human Research approved the study. RESULTS: after surgery, we observed a reduction of hypernasality in 84% of the patients from group I, and in 73% of the patients from group II. Reduction of nasalance scores were observed in 52% of the group I cases and in 43% of the group II. CONCLUSION: secondary palatoplasty performed with intravelar veloplasty led to improvement in nasality in most of the analyzed patients. The results further demonstrated that surgery was more effective in patients with minor defects in velopharyngeal closure

Phase II trial of humanized anti-Lewis Y monoclonal antibody for advanced hormone receptor-positive breast cancer that progressed following endocrine therapy

OBJECTIVES: The Lewis-Y antigen is expressed in 44%-90% of breast cancers (BCs). The expression of the antigen in carcinoma tissue differs from that in normal tissues. This study aimed to evaluate the clinical benefit of the humanized anti-Lewis Y monoclonal antibody, hu3S193, in advanced hormone receptor-positive and Lewis Y-positive BC after administration of endocrine therapy (ET). METHODS: A single-arm phase II study was conducted in seven centers. Patients with advanced hormone receptor-positive BC who failed first-line ET were included. The inclusion criterion was the observation of tumoral expression of the Lewis Y antigen during immunohistochemistry. The treatment comprised hu3S193 antibody administration at weekly intravenous doses of 20 mg/m2 for 8-week cycles. The primary endpoint was the clinical benefit rate. ClinicalTrials.gov NCT01370239. RESULTS: The study stopped accrual following an unplanned interim analysis as the hu3S193 antibody lacked sufficient activity to justify continuation of the study. Twenty-two patients were enrolled, of whom 21 were included in the efficacy analysis. The clinical benefit rate was 19%, with four patients presenting with stable disease after 24 weeks. One patient with prolonged stable disease received medication for over 2 years. No partial or complete responses were observed. The median time to progression and overall survival was 5.4 and 37.5 months, respectively. CONCLUSIONS: The humanized anti-Lewis Y monoclonal antibody, hu3S193, exhibited insufficient activity in this cohort. However, the possibility of activity in a more strictly selected subgroup of patients with higher levels of Lewis Y tumoral expression cannot be overlooked

Pediatric COVID-19 patients in South Brazil show abundant viral mRNA and strong specific anti-viral responses

COVID-19 manifests as a milder disease in children than adults, but the underlying mechanisms are not fully characterized. Here we assess the difference in cellular or humoral immune responses of pediatric and adult COVID-19 patients to see if these factors contribute to the severity dichotomy. Children’s non-specific immune profile is dominated by naive lymphocytes and HLA-DRhighCX3CR1low dendritic cells; meanwhile, children show strong specific antibody and T cell responses for viral structural proteins, with their T cell responses differing from adults by having weaker CD8+TNF+ T cells responses to S peptide pool but stronger responses to N and M peptide pools. Finally, viral mRNA is more abundant in pediatric patients. Our data thus support a scenario in which SARS-CoV-2 infected children contribute to transmission yet are less susceptible to COVID-19 symptoms due to strong and differential responses to the virus

Feed efficiency of lactating nellore cows: 2. Correlation among phases and between models

The objective of the study was to examine the classification of cows based on residual feed intake (RFI) obtained during the first, second and total lactation phase, fitting models which included or not fat thickness and milk production. Twenty-seven lactating Nellore cows, 38 ± 0.83 months of age and 509 ± 32 kg of body weight, were evaluated 22 ± 5 days after calving in a collective pen equipped with GrowSafe® Systems during 75 ± 12 days (phase 1) and 77 ± 6 days (phase 2). The forage-based diet (dry matter basis) consisted of 90% corn silage, 8.5% soybean meal and 1.5% mineral salt plus urea. Dry matter intake (DMI) was obtained as the mean of all valid days of feed intake during the test period (12.7 ± 1.2 kg DM for phase 1; 13.0 ± 1.4 kg DM for phase 2; and 12.9 ± 1.25 kg DM for the total phase), and average daily gain (ADG) was obtained as a regression of body weights on days on test (0.359 ± 0.242 kg day-1 for phase 1; 0.716 ± 0.263 kg day-1 for phase 2; and 0.591 ± 0.148 kg day-1 for the total phase). Ultrasonic fat thickness was evaluated in five anatomic sites, and the average of fat thickness (FT) was obtained (7.81 ± 1.45 mm for phase 1; 12.68 ± 2.03 mm for phase 2, and 10.24 ± 1.64 mm for the total phase). Cows were machine milked three times after calving (63 ± 5 days in milk; 85 ± 5 dim; and 151 ± 6 dim), after intravenous injection of 20 Ul of oxytocin, quantifying the 6 h milk production to estimate 24 h milk production. The 24 h energy-corrected milk production (24hMP) was obtained by 24hMP = (0.327 x kg milk production) + (12.95 x kg fat) + (7.20 x kg protein), using fat and protein percentage of milk. The 24hMP values of cows were 10.1 ± 2.85 kg day-1, 10.7 ± 2.68 kg day-1 and 10.27 ± 2.80 kg day-1 in phase 1, phase 2 and total phase. Two models were tested for RFI calculation: model 1 - DMI = ADG + metabolic body weight (BW0.75) + error; and model 2 - DMI = ADG + PV0.75 + FT + 24hMP + error. The RFI values obtained were: phase 1 (RFI1 and RFI1fm: 0 ± 1.05 kg day-1 and R2 = 0.17; 0 ± 1.01 kg day-1 and R2 = 0.22); phase 2 (RFI2 and RFI2fm: 0 ± 1.06 kg day-1 and R2 = 0.46; 0 ± 1.02 kg day-1 and R2 = 0.45); and total phase (RFIt and RFItfm: 0 ± 1.05 kg day-1 and R2 = 0.29; 0 ± 0.92 kg day-1 and R2 = 0.45). Analyses of ranking correlation were conducted using PROC CORR by SAS®. For the phases, RFI correlations were positive and ranged from moderate to high (0.59 to 0.91). The smallest correlation was 0.59 between RFI1fm and RFI2fm and the largest was 0.91 between RFI2 and RFIt. The correlation between RFI1 and RFI2 was moderate (0.74). The models to calculate RFI, correlations between RFI adjusted or not for FT and 24hMP were 0.96, 0.96 and 0.88 for phase 1, phase 2 and total phase, suggesting little importance of FT and 24hMP variables to explain the DMI variation of these lactating cows. These results showed that the classification of primiparous lactating Nellore cows for RFI differs between the first and second lactation phases. An unexpected result was the low coefficient of determination of the RFI models for phase 1, in which no effect was significant to explain the DMI variation. As expected, cow metabolic body weight was the main effect of RFI models for phase 2 and the total phase. The average fat thickness was not relevant to explain the DMI variation of primiparous lactating Nellore cows

Feed efficiency of lactating Nellore cows: 1. Correlation of component traits between two the lactation phases

The objective of the study was to evaluate the correlations of dry matter intake (DMI), average daily gain (ADG), metabolic weight (BW0.75), fat thickness and corrected milk production obtained between the two lactation phases. Twenty-seven lactating Nellore cows, 38 ± 0.83 months of age and 509 ± 32 kg of body weight, were evaluated 22 ± 5 days after calving in a collective pen equipped with GrowSafe® Systems during 75 ± 12 days (phase 1), 77 ± 6 days (phase 2) and 152 ± 6 days (total phase). The forage-based diet (dry matter basis) consisted of 90% corn silage, 8.5% soybean meal and 1.5% mineral salt plus urea. DMI was obtained as the mean of all valid days of feed intake during the test period (12.7 ± 1.2 kg DM for phase 1; 13.0 ± 1.4 kg DM for phase 2; and 12.9 ± 1.25 kg DM for the total phase), and ADG was obtained as a regression of body weights on days on test (0.359 ± 0.242 kg day-1 for phase 1; 0.716 ± 0.263 kg day-1 for phase 2; and 0.591 ± 0.148 kg day-1 for the total phase). BW0.75 was obtained by the equation: [α + (ADG test x 0.5 x days)]0.75 (110 ± 5 kg for phase 1, 108 ± 6 kg for phase 2, and 113 ± 5 kg for the total phase), where α is the intercept of the regression equation and represents the initial weight. Ultrasonic fat thickness was evaluated in five anatomic sites, and average of fat thickness (FT) was obtained (7.81 ± 1.45 mm for phase 1; 12.68 ± 2.03 mm for phase 2, and 10.24 ± 1.64 mm for the total phase). Cows were machine milked three times after calving (63 ± 5 days in milk; 85 ± 5 dim; and 151 ± 6 dim), after intravenous injection of 20 Ul of oxytocin, quantifying the 6 h milk production, to estimate 24 h milk production. The 24 h energy-corrected milk production (24hMP) was obtained by 24hMP = (0.327 x kg milk production) + (12.95 x kg fat) + (7.20 x kg protein), using fat and protein percentage of milk. The 24hMP values of cows were 10.1 ± 2.85 kg day-1, 10.7 ± 2.68 kg day-1 and 10.27 ± 2.80 kg day-1 in phase 1, phase 2 and total phase. All variables were obtained for phase 1 (DMI1, ADG1, BW0.751, FT1 and 24hMP1), phase 2 (DMI2, ADG2, BW0.752, FT2 and 24hMP2) and for the total phase (DMIt, ADGt, BW0.75t, FTt and 24hMPt). Analyses of ranking correlation were conducted using PROC CORR by SAS®. The DMI correlations ranged from moderate to high: DMI1 and DMI2 (0.69), DMI1 and DMIt (0.88), and DMI2 and DMIt (0.95). High correlations were observed between BW0.751 and BW0.752 (0.86); BW0.751 and BW0.75t (0.98); and BW0.752 and BW0.75t (0.85). Among ADG, correlations were low and non-significant, except for the correlation between ADG2 and ADGt (0.64), suggesting that phase 1 is different from phase 2. In phase 1, lactating cows have higher energy expenditure with milk production for the suckling calves, in addition to energy expenditure for maintenance. High correlations of fat thickness between the lactation phases were observed: FT1 and FT2 (0.77), FT1 and FTt (0.92), and FT2 and FTt (0.96). The correlations between 24hMP varied from low to high: 0.21 between 24hMP1 and 24hMP2; 0.88 between 24hMP1 and 24hMPt; and 0.65 between 24hMP2 and 24hMPt. These results indicate that reranking exists in Nellore cows between the two lactation phases