The effect of PD-L1 testing on the cost-effectiveness and economic impact of immune checkpoint inhibitors for the second-line treatment of NSCLC.

BACKGROUND: Immune checkpoint inhibitors improve outcomes compared with chemotherapy in lung cancer. Tumor PD-L1 receptor expression is being studied as a predictive biomarker. The objective of this study was to assess the cost-effectiveness and economic impact of second-line treatment with nivolumab, pembrolizumab, and atezolizumab with and without the use of PD-L1 testing for patient selection. DESIGN: We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and second-line immunotherapy versus docetaxel. The model used outcomes data from randomized clinical trials (RCTs) and drug acquisition costs from the United States. Thereafter, we used epidemiologic data to estimate the economic impact of the treatment. RESULTS: We included four RCTs (2 with nivolumab, 1 with pembrolizumab, and 1 with atezolizumab). The incremental quality-adjusted life year (QALY) for nivolumab was 0.417 among squamous tumors and 0.287 among non-squamous tumors and the incremental cost-effectiveness ratio (ICER) were $155 605 and $187 685, respectively. The QALY gain in the base case for atezolizumab was 0.354 and the ICER was $215 802. Compared with treating all patients, the selection of patients by PD-L1 expression improved incremental QALY by up to 183% and decreased the ICER by up to 65%. Pembrolizumab was studied only in patients whose tumors expressed PD-L1. The QALY gain was 0.346 and the ICER was $98 421. Patient selection also reduced the budget impact of immunotherapy. CONCLUSION: The use of PD-L1 expression as a biomarker increases cost-effectiveness of immunotherapy but also diminishes the number of potential life-years saved.

Chylous ascites due to signet ring cell gastric adenocarcinoma.

UNLABELLED: "Chylous ascites is a rare presentation of peritoneal effusion. The signet ring cell gastric adenocarcinoma is also relatively rare presentation of gastric cancer. We present a quite rare case of chylous ascites associated with signet ring cell gastric adenocarcinoma. CASE REPORT: a 47-years-old Caucasian man presented to our emergency department with abdominal distention. The abdominal ultra-sound showed high volume ascites and the diagnostic paracentesis revealed milk-like peritoneal fluid rich in triglycerides. He was underwent to medium chain triglycerides based diet, total parenteric diet and treatment with somatostatin without response. Due to presented digestive hemorrhagic events, upper digestive endoscopy was performed and revealed signet ring cells gastric adenocarcinoma on biopsy. The patient died in disseminated intravascular coagulation context. CONCLUSION: chylous asicites is a rare presentation of ascites and it may be associated with abdominal neoplasm. The prompt diagnosis is important for optimize the etiology evaluation and therapeutically approach."

Reproductive biology of pequira Bryconamericus stramineus (Eigenmann, 1908) in Funil Reservoir-MG, Brazil.

In order to evaluate aspects of reproductive biology of the "pequira" ( Bryconamericus stramineus) in the elevator of the Funil Dam - MG, fish capture was carried out from November 2008 to January 2009 and 317 individuals were collected. The mean standard length (SL) of the population was 4.96 cm and mean weight 1.80 g. The females had SL of 5.0 cm, while males had a SL of 4.6 cm. A sex ratio of 2.20: 1 (females: male) was observed. Our results show that 73% of the individuals analyzed were considered adults. The species presented low fecundity, mean of 470.9 oocytes per female and a mean diameter of 221.08 µm, with an increase in oocyte diameter over the evaluation period. The length of the first gonadal maturation was estimated at 5.0 cm. The results obtained in this work suggest that the reproductive cycle of the species occurs in the analyzed period. Although this species does not have migratory reproductive habits, the presence of adults in the reproductive stage was observed in the transposition area, which suggests a search for new environments for spawning.

Reproductive biology of pequira Bryconamericus stramineus (Eigenmann, 1908) in Funil Reservoir-MG, Brazil / Biologia reprodutiva da Pequira Bryconamericus stramineus (Eigenmann, 1908) no reservatório de Funil-MG, Brasil

Abstract In order to evaluate aspects of reproductive biology of the "pequira" ( Bryconamericus stramineus) in the elevator of the Funil Dam - MG, fish capture was carried out from November 2008 to January 2009 and 317 individuals were collected. The mean standard length (SL) of the population was 4.96 cm and mean weight 1.80 g. The females had SL of 5.0 cm, while males had a SL of 4.6 cm. A sex ratio of 2.20: 1 (females: male) was observed. Our results show that 73% of the individuals analyzed were considered adults. The species presented low fecundity, mean of 470.9 oocytes per female and a mean diameter of 221.08 μm, with an increase in oocyte diameter over the evaluation period. The length of the first gonadal maturation was estimated at 5.0 cm. The results obtained in this work suggest that the reproductive cycle of the species occurs in the analyzed period. Although this species does not have migratory reproductive habits, the presence of adults in the reproductive stage was observed in the transposition area, which suggests a search for new environments for spawning.

Resumo Com o objetivo de avaliar aspectos da biologia reprodutiva da pequira Bryconamericus stramineus no elevador da represa do Funil - MG foram realizadas capturas entre os meses de novembro de 2008 a janeiro de 2009, sendo coletados 317 indivíduos. O comprimento padrão (CP) médio da população foi de 4,96 cm e peso médio de 1,80 g. As fêmeas apresentaram CP de 5,0 cm, enquanto que os machos obtiveram um CP de 4,6 cm. Foi observada proporção sexual de 2,20:1(fêmeas:macho). Dos indivíduos analisados, 73% foram considerados adultos. A espécie apresentou baixa fecundidade, com média de 470,9 ovócitos por fêmea e diâmetro médio de 221,08 μm, ocorrendo aumento no diâmetro de ovócitos com o decorrer do tempo no período avaliado. O comprimento de primeira maturação gonadal foi estimado em 5,0 cm. Os resultados obtidos neste trabalho sugerem que o ciclo reprodutivo da espécie ocorre no período analisado. Embora esta espécie não tenha hábitos reprodutivos migratórios, a presença de adultos no estágio reprodutivo foi observada na área de transposição, o que sugere a busca de novos ambientes para a reprodução.

Reproductive biology of pequira Bryconamericus stramineus (Eigenmann, 1908) in Funil Reservoir-MG, Brazil

Abstract In order to evaluate aspects of reproductive biology of the pequira ( Bryconamericus stramineus) in the elevator of the Funil Dam - MG, fish capture was carried out from November 2008 to January 2009 and 317 individuals were collected. The mean standard length (SL) of the population was 4.96 cm and mean weight 1.80 g. The females had SL of 5.0 cm, while males had a SL of 4.6 cm. A sex ratio of 2.20: 1 (females: male) was observed. Our results show that 73% of the individuals analyzed were considered adults. The species presented low fecundity, mean of 470.9 oocytes per female and a mean diameter of 221.08 m, with an increase in oocyte diameter over the evaluation period. The length of the first gonadal maturation was estimated at 5.0 cm. The results obtained in this work suggest that the reproductive cycle of the species occurs in the analyzed period. Although this species does not have migratory reproductive habits, the presence of adults in the reproductive stage was observed in the transposition area, which suggests a search for new environments for spawning.

Resumo Com o objetivo de avaliar aspectos da biologia reprodutiva da pequira Bryconamericus stramineus no elevador da represa do Funil - MG foram realizadas capturas entre os meses de novembro de 2008 a janeiro de 2009, sendo coletados 317 indivíduos. O comprimento padrão (CP) médio da população foi de 4,96 cm e peso médio de 1,80 g. As fêmeas apresentaram CP de 5,0 cm, enquanto que os machos obtiveram um CP de 4,6 cm. Foi observada proporção sexual de 2,20:1(fêmeas:macho). Dos indivíduos analisados, 73% foram considerados adultos. A espécie apresentou baixa fecundidade, com média de 470,9 ovócitos por fêmea e diâmetro médio de 221,08 m, ocorrendo aumento no diâmetro de ovócitos com o decorrer do tempo no período avaliado. O comprimento de primeira maturação gonadal foi estimado em 5,0 cm. Os resultados obtidos neste trabalho sugerem que o ciclo reprodutivo da espécie ocorre no período analisado. Embora esta espécie não tenha hábitos reprodutivos migratórios, a presença de adultos no estágio reprodutivo foi observada na área de transposição, o que sugere a busca de novos ambientes para a reprodução.

Effect of cryopreservant combinations on the motility and morphology of curimba (Prochilodus lineatus) sperm.

This study investigated the application of intra- and extra-cellular cryoprotectant combinations on the quality of curimba Prochilodus lineatus semen subjected to cryopreservation. Semen treatments were tested with 8% DMSO or methanol as intracellular cryoprotectant, 5% egg yolk or lactose as extracellular cryoprotectant and 5% BTS. These cryoprotectant combinations are suitable for curimba but have not been tested at the lesser concentrations proposed or in combination with BTS. Semen samples collected from 19 curimbas were diluted into one of four cryoprotectant combinations: DMSO+yolk; DMSO+lactose; methanol+yolk; and methanol+lactose. After dilution, semen samples were cryopreserved in 0.5 mL straws for 10 days in a liquid nitrogen tank. Semen was thawed in a water bath at 60°C for 8s. We evaluated the quality of fresh, diluted (pre-freezing) and post-freezing semen according to sperm motility rate (%) and duration (s). Sperm morphology was also analyzed in thawed semen. Sperm motility rate decreased progressively after dilution and thawing. The motility rate in post-freezing semen was higher in the treatments using DMSO+lactose and methanol+yolk. Sperm motility duration in post-freezing sperm was greater in the treatments using methanol rather than DMSO as intracellular cryoprotectant, irrespective of the extracellular cryoprotectant used. Abnormality frequency in thawed sperm was less in semen treated with egg yolk than with lactose. Thus the use of methanol intracellular cryoprotectant is recommended along with yolk extracellular cryoprotectant in the cryopreservation process for curimba semen.

Role of bacterial Mn-cofactored superoxide dismutase in oxidative stress responses, nasopharyngeal colonization, and sustained bacteremia caused by Haemophilus influenzae type b.

Haemophilus influenzae type b, a causative agent of bacterial sepsis and meningitis in young children, contains a single superoxide dismutase (SOD), a cytoplasmic MnSOD. To study the role of this enzyme, a chromosomal sodA::lacZ mutant (M-2) was constructed. M-2 had an increased sensitivity towards oxygen and the redox-active agent paraquat. A 3.4-fold increase in sodA-lacZ expression was found in M-2 grown with oxygen supply rates between 3 and 36 mmol of O2/liter/h. In similar experiments with the wild type, assaying SodA activity, a 3.1-fold increase was found. Both the wild type and M-2 grew best at the lowest oxygen supply rate tested, consistent with the notion that H. influenzae prefers a more anaerobic environment. In the infant rat model of infection, the ability of M-2 to colonize the nasopharynx was found to be impaired, but its ability to cause invasive disease was unaffected. This suggests that after invasion, the growth disadvantage imposed by a SodA- phenotype is not limiting.

Effect of the thyroidectomy on male rats fed two antagonist lipid diets: I. Physiological aspects

Male rats fed an n-6 polyunsaturated fatty acid (PUFA)-rich diet A or an n-3 PUFA-rich diet B were subjected to a surgical thyroidectomy or to a sham-operation (control animals). Thyroidectomy caused a lesser daily increase of body weight in both dietary groups. The diet A rats showed in average greater values of body weight than diet B rats, for control and thyroidectomized animals. After 30 days of experiment thyroidectomy caused no effect on the relative weight (g/100g body weight) of liver in both dietary groups. However, it increased the relative weight) of gastrocnemius (p<0.05) and brain (p<0.001) in both dietary groups, and it decreased the relative weight of heart in both dietary groups, and it decreased the relative weight of heart in diet A (NS) and in diet B (p<0.05) groups. The relative weights of heart, gastrocnemius, liver and brain of control and thyroidectomized rats of diet A groups were lower than respective organs of diet B groups. Thyroidectomy did not affect the level of plasma proteins of diet B rats was higher than diet A rats, for controls or thyroidectomized animals. Iodine uptake by thyroid gland, the plasma level of T3 of diet B control rats were significant higher thand diet A control rats, but the plasma level of T4 of diet A control rats was higher than diet B control rats (NS). These results suggested that the thyroidectomy and or lipid diets may alter the rat development as well the ingestion of antagonist lipid diets may alter thyroid gland functions

The effect of the thyroidectomy in male rats fed two antagonist lipid diets: II. The fatty acid content of lipids of plasma and mitochondria of liver and brain

Male rats subjected to surgicl thyroidectomy showed alteration in the content of fatty acids (FA) of plasma and mitochondria of liver and brain lipids in comparison to control animals (sham-operated). Those alterations depend of the kind of dietary fat intake. Control and thyroidectomized rats fed an n-6 polyunsaturated fatty acid (PUFA)-rich diet A or an n-3 PUFA-rich diet B. Thyroidectomy, independently of kind of diet, did not cause any alteration on the P/S ratio in plasma or brain mithocondria. However, it caused an increase on the P/S ratio in liver mithochondria, more evident in the dietary group B. This fact may suggest that the absence of thyroid hormones would induce a higher incorporation of PUFAs in liver lipids. Thyroidectomy caused a decrease of linoleic acid (LA) content in plasma of both dietary groups but it caused an increase of LA in diet A brain mitochondria groups. The plasma FA content, although depends on the source of fat intake, was not a mere reflection of the diet FA ingested. As the thyroidectomy also changed the content of plasma FA, it is possible to postulate that the plasma FA should be actually a reflection of the FA content of endogenous lipds

The effect of thyroidectomy in male rats fed two antagonist lipid diets: III. The liver and brain mitochondrial ATPase activity

The liver and brain mitochondrial ATPase activity of surgical thyroidectomized male rats fed two antagonist lipid diets, an n06 polyunsaturated fatty (PUFA)-rich diet A or an n-3 PUFA-rich diet B, during 30 days, was different in comparison to the respective controls (sham-operated animals). Thyroidectomy did not change the diet A liver and diet B brain ATPase activity, but it increased the diet B liver ATPase (p<0.001) and decreased the diet A brain ATPase (p<0.001). The ATPase activity was also altered in function of used diets, with the exception of thyroidectomized rats in liver. The ATPase of diet A control rats was higher than the enzyme of diet B control rats in liver (p<0.001) and brain (p<0.001). The ATPase of diet A thyroidectomized rats was higher than the diet B thyroidectomized rats ATPase (p<0.005)

The effect of thyroidectomy on male rats fed two antagonist lipid diets. IV. The fatty acid content of mitochondrial lipids of heart and gastrocnemic muscles

The fatty acid (FA) contents of heart and gatrocnemic muscle mitochondrial lipids of thyroidecromized and control (sham-operated) were analyzed. Animals were fed either an n-6 polyunsaturated (PUFA)-rich diet A or an n- PUFA-rich diet B during 30 days. It was observed alteraions in the composition of FA of those cell organelles caused by the absence of the thyroid gland. Some of these alterations were dependent of the type of used diet. Thyroidecromy caused an increase of P?S ratio in heart and gastrocnemic muscle but only for animals fed diet B. Thyroidectomy caused an increase of n-6/n-3 ratio in heart of rats fed diet A and in gastrocnemic muscle of rats fed diet B and it caused a decrease of n-6/n-3 ratio of heart of rats fed diet A and in gastrocnemic muscle of rats fed diet B. The absence of thyroid gland in some way may interfer in the FA metabolism and in the rate of FA incorporation into endogeneous lipids but in a different process dependent of type of tissue and of used lipid diet

The effect of the thyroidectomy in male rats fed two antagonist lipid diets. V. The mitochondrial ATPase activity of heart and gastrocnemic muscles

The mitochondrial ATPase activity of heart and gastrocnemic muscles of thyroidectomized and control rats was determined. Some rats were fed an n-6 polyunsaturated fatty acids (PUFA)-rich diet A and others were fed an n-3PUFA-rich diet B, during 30 days. The heart mitochondrial ATPase activity of rats fed diet A was higher than of rats fed diet B in both thyroidectomized (p < 0.01) and control (p < 0.05) groups. The thyroidectomy induced an increase of heart mitochondrial ATPase activity in both dietary groups (p < 0.01). The thyroidectomy also induced an increase in gastrocnemic mitochondrial ATPase activity in diet B group, but it induced a decrease in ATPase activity in diet A group. The data suggest that the dietary lipids and the absence of thyroid gland induce changes in mitochondrial ATPase activity in heart and gastrocnemic muscles, confirming the same observations previously y described for the effect of thyroidectomy and diet in rat liver and brain (9)