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1.
Braz. j. biol ; 82: e237040, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1249252

RESUMO

Abstract This investigation presents the food and feeding activity of and endangered riverine catfish Rita rita, during February 2017-January 2018. A total of 225 fish individuals was analyzed for stomach contents by characterizing the dominant food items and morphometric features. The results divulged ten major food items consumed, preferably fish scales and eggs, teleost fishes, copepods, cladocerans, rotifers, and mollusks. Total length and body weight of fish varied between 9-34 cm (20.53 ± 6.90 cm) and 10-400 g (9125.94 ± 102.07 g), respectively. The index of relative importance (IRI%) showed the importance of rotifers over the other food items. Morisita's index of diet overlap indicated seasonal variations in catfish diets with summer and monsoon displaying the least overlap, while maximum overlap during monsoon and winter seasons. The non-metric multidimensional scaling (nMDS) indicated the close association between the food items available during summer and winter seasons with a significant difference among the seasons (ANOSIM, R = 0.638, P = 0.013). Levin's niche breadth index arranged in the order of 0.88>0.81>0.78>0.63>0.43 for the size classes of V, IV, III, II and I, respectively. The PCA explained 95.39% of the total variance among the food items and fish size groups. Small-sized fish individuals displayed a greater correlation with food items suitable for their mouth size. In conclusion, the variety and frequency of food items recorded indicated considerable feeding plasticity and opportunistic feeding behavior with a shift from carnivorous to omnivorous feeding nature. This study could render useful information on the food and feeding habits of R. rita and provide background for preparing its diet for future aquaculture practices.


Resumo Esta investigação apresenta a alimentação e a atividade alimentar de bagres ribeirinhos Rita rita ameaçados de extinção, no período de fevereiro de 2017 a janeiro de 2018. Um total de 225 peixes foi analisado quanto ao conteúdo do estômago, caracterizando os itens alimentares dominantes e as características morfométricas. Os resultados apresentaram dez principais itens alimentares consumidos, preferencialmente escamas e ovos de peixes, teleósteos, copépodes, cladóceros, rotíferos e moluscos. O comprimento total e o peso corporal dos peixes variaram entre 9-34 cm (20,53 ± 6,90 cm) e 10-400 g (9125,94 ± 102,07 g), respectivamente. O índice de importância relativa (IRI%) mostrou a importância dos rotíferos sobre os demais itens alimentares. O índice de sobreposição de dieta de Morisita indicou variações sazonais nas dietas de bagres no verão e nas monções, exibindo a menor sobreposição, enquanto a sobreposição máxima ocorreu durante as estações das monções e do inverno. A escala multidimensional não métrica (nMDS) indicou a estreita associação entre os itens alimentares disponíveis durante o verão e o inverno, com uma diferença significativa entre as estações (ANOSIM, R = 0,638, P = 0,013). O índice de amplitude de nicho de Levin foi organizado na ordem de 0,88 > 0,81 > 0,78 > 0,63 > 0,43 para as classes de tamanho de V, IV, III, II e I, respectivamente. O PCA explicou 95,39% da variação total entre os itens alimentares e os grupos de tamanho de peixes. Peixes de pequeno porte apresentaram maior correlação com itens alimentares adequados ao tamanho da boca. Em conclusão, a variedade e a frequência dos itens alimentares registrados indicaram plasticidade alimentar considerável e comportamento alimentar oportunista, com uma mudança da natureza carnívora para onívora. Este estudo pode fornecer informações úteis sobre os hábitos alimentares e de alimentação de R. rita e apresentar subsídios para a preparação de sua dieta em futuras práticas de aquicultura.

2.
Braz. j. biol ; 81(4): 1036-1049, Oct.-Dec. 2021. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1153451

RESUMO

Abstract The primary objective of this study was to investigate the seasonal fish and crustacean variations concerning taxonomic composition, species richness, and diversity in sandy beach habitat. For this purpose, we investigated the Sonmiani Hor lagoon area during four distinct seasons, i.e., northeast (NE) monsoon, pre-monsoon, south-west (SW) monsoon, and post-monsoon for one year. During each haul, the net was pulled about 100m along the beach in 0.5m depth. The results showed a strong linear correlation between the diversity index and equitability in fishes (r = 0.978). The diversity index was strong negatively correlated with the abundance and biomass (r = -0.978, -0.972, respectively). The physical attributes like sea surface water temperature and salinity showed a strong negative effect on species assemblages (r = -0.981 and -0.943, respectively). The mean air and water temperature illustrated approximately 3°C difference during NE and pre-monsoon seasons. However, salinity, pH, and electrical conductivity did not show any significant seasonal variabilities. Under the ecological indices, the fish species displayed higher diversity (H' = 3.19) during SW monsoon, whereas the lowest diversity was observed during pre-monsoon (H' = 1.58). The equitability and species richness, however, remained more noticeable during SW monsoon (J' = 0.81). The total number of individuals of fish and crustaceans reached 4799 with 3813 fish individuals and 986 individuals of crustaceans. A total of 27 families of fish while five crustacean families comprising of 30 genera and 38 fish species while ten genera and 17 species of crustaceans were recorded. Liza subviridis displayed the highest abundance among the sampled fish species. In conclusion, fish species constituted a significant part of the coastal fauna in the study area. The seasonal variations displayed distinct variations in fish species composition and diversity.


Resumo O objetivo principal deste estudo foi investigar as variações sazonais de peixes e crustáceos em relação à composição taxonômica, riqueza de espécies e diversidade no habitat de praias arenosas. Para esse fim, investigamos a área da lagoa Sonmiani Hor durante quatro estações distintas, ou seja, monção nordeste (NE), pré-monção, monção sudoeste (SW) e pós-monção, por um ano. Durante cada transporte, a rede foi puxada cerca de 100 m ao longo da praia, a 0,5 m de profundidade. Os resultados mostraram uma forte correlação linear entre o índice de diversidade e a equitabilidade de peixes (r = 0,978). O índice de diversidade apresentou forte correlação negativa com a abundância e a biomassa (r = -0,978 e -0,972, respectivamente). Os atributos físicos, como temperatura da água da superfície do mar e salinidade, apresentaram forte efeito negativo sobre o conjunto de espécies (r = -0,981 e -0,943, respectivamente). A temperatura média do ar e da água teve uma diferença de aproximadamente 3 °C durante a monção NE e a pré-monção. No entanto, salinidade, pH e condutividade elétrica não apresentaram variabilidade sazonal significativa. A respeito dos índices ecológicos, as espécies de peixes apresentaram maior diversidade (H' = 3,19) durante a monção SW, enquanto a menor diversidade observada foi na pré-monção (H' = 1,58). A equitabilidade e a riqueza de espécies, no entanto, permaneceram mais perceptíveis durante a monção SW (J' = 0,81). O número total de peixes e crustáceos foi de 4.799, com 3.813 peixes e 986 crustáceos. Foram registradas 27 famílias de peixes e 5 famílias de crustáceos, com 30 gêneros e 38 espécies de peixes, além de 10 gêneros e 17 espécies de crustáceos. Liza subviridis apresentou a maior abundância entre as espécies de peixes amostradas. Em conclusão, as espécies de peixes constituíram uma parte significativa da fauna costeira na área de estudo. As variações sazonais apresentaram variações distintas na composição e diversidade das espécies de peixes.

3.
Braz J Biol ; 83: e247701, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468529

RESUMO

Staphylococcus aureus is an important foodborne pathogen associated to food intoxication and other multiple infections in human being. Its presence in salted food is a serious issue due to its salt tolerance potential. A study was conducted to analyze the presence of enterotoxins producing drug resistance S. aureus in salted sea fish from Gwadar. Freshly persevered samples (n=50) of salted fish were subjected to analyze the presence of S. aureus using 16S rRNA and Nuc genes primers. The isolates were then evaluated for drug resistance and enterotoxins producing potential using specific primers for MecA (methicillin resistance gene), (SEA) staphylococcal enterotoxin A and (SEB) staphylococcal enterotoxin B genes. Total 13/50 (26%) of the samples were found positive for the presence of S. aureus, preliminary confirmed with biochemical profiling and finally with the help of target genes presence. The isolates were found showing 100% resistant to methicillin, which were molecularly confirmed by the presence of MecA gene present in genome. The isolates 5/13 (38%) were positive for SEA and 3/13 (23%) for SEB genes, whereas 2/13 (15%) were confirmed having both SEA and SEB genes in its genome. It was also confirmed that all the isolates were capable to form biofilm over the glass surfaces. It was concluded that the study confirmed the presence of enterotoxigenic methicillin resistance Staphylococcus aurous (MRSA) in salted fish product, that poses gross food safety concern. Preventive and control measures are necessary to handle this serious food safety concern.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Produtos Pesqueiros , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , RNA Ribossômico 16S , Staphylococcus aureus/genética
4.
Braz J Biol ; 83: e250789, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468536

RESUMO

The present study was carried out to determine incidence of overweight and obesity in Pakistani servicemen with reference to their area of duty, feeding habits and also to identify risk factors. Accordingly, 2,501 servicemen selected from all over Pakistan using multiple stage stratified sampling protocol. Nutrition assessment performed using body mass index (BMI), waist to hip ratio (WHR) and dietary assessment using food frequency questionnaire. Collected data was analyzed using the SPSS version 25. Regression was used to find risk factors of obesity and WHR. Results indicated that about 1/4th of servicemen were smokers. Approximately, 1/5th of them were overweight and about one quarter were eating fruits and vegetables for <3 days/ week and <4 days/week, respectively. Only 1/3rd of them were physically active for at least <40 minutes per day. Age and fruits intake were significantly predicting BMI with a direct relation and vegetable intake was negatively correlated to BMI of the servicemen. Age and rank were significant predictors of WHR while, physical activity was negatively correlated to WHR. It is concluded and suggested from our study that there is a need to modify eating patterns and habits as well as improving physical activity on daily basis for healthy and long life of the servicemen.


Assuntos
Comportamento Alimentar , Avaliação Nutricional , Estudos Transversais , Hábitos , Paquistão , Estudos Prospectivos
5.
EuroIntervention ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34503942

RESUMO

BACKGROUND: Retrievable stents and aspiration catheters have been developed to provide more effective arterial recanalisation in acute ischaemic stroke. AIMS: The aim of this analysis was to test the effect of mechanical thrombectomy on mortality and long-term neurological outcome in patients presenting with acute large-vessel anterior circulation ischaemic stroke. METHODS: A structured search identified randomised controlled trials of thrombectomy (using a retrievable stent or aspiration catheter) versus control on a background of medical therapy which included intravenous thrombolysis if appropriate. The primary endpoint was disability at 90-day follow-up as assessed by the modified Rankin scale (mRS). Secondary endpoints included all-cause mortality and symptomatic intracranial haemorrhage. A Bayesian mixed-effects model was used for analysis. RESULTS: Twelve (12) trials met the inclusion criteria, comprising a total of 1,276 patients randomised to thrombectomy and 1,282 patients to control. Randomisation to thrombectomy significantly reduced disability at 90 days (OR 0.52, 95% credible interval 0.46 to 0.61, probability(control better)<0.0001). Furthermore, thrombectomy reduced the odds of functional dependence at 90 days, indicated by an mRS score >2 (OR 0.44, CrI 0.37 to 0.52, pr<0.0001). Thrombectomy reduced all-cause mortality at 90 days (16.1% vs 19.2%, OR 0.81, 95% CrI 0.66 to 0.99, pr=0.024). The frequency of symptomatic intracranial haemorrhage was similar between thrombectomy (4.2%) and control (4.0%) (OR 1.12, 95% CrI 0.76 to 1.68, pr=0.72). CONCLUSIONS: In patients with an acute anterior circulation stroke, modern device thrombectomy significantly reduces death and subsequent disability. The magnitude of these effects suggests that universal access to this treatment strategy should be the standard of care.

6.
AANA J ; 89(5): 384-390, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34586991

RESUMO

This study examined the level of perceived cultural competence of student registered nurse anesthetists (SRNAs) in Illinois and made educational recommendations. A descriptive, cross-sectional study was completed using the Clinical Cultural Competency Questionnaire (CCCQ) to evaluate the perceived level of cultural competence among SRNAs in Illinois. Four domains of clinical cultural competency--knowledge, skills, attitudes (awareness), and encounters--were evaluated and reported. The survey response rate was 16.7% (N=57). A significant positive correlation was observed between cultural knowledge and age (P=.03). There was a significant difference in cultural knowledge between students attending a nurse anesthesia program in suburban Northeastern Illinois and students attending a large, urban university in the city of Chicago, with CCCQ knowledge mean rank scores of 38.44 and 13.77, respectively. The overall level of perceived clinical cultural competence of SRNAs was low: mean (SD)=3.13 (0.54); range=2.17 to 4.89. The authors concluded that SRNAs need additional cultural education and training in their program of study to enhance their perceived level of cultural competence and to deliver culturally competent anesthesia care. The desire to become culturally competent coupled with deficient levels of cultural knowledge among SRNAs merits further work.

7.
Int J Cardiol ; 342: 7-14, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34358553

RESUMO

OBJECTIVES: Adenosine hyperemia is an integral component of the physiological assessment of obstructive coronary artery disease in patients with chronic coronary syndrome (CCS). The aim of this study was to compare systemic, coronary and microcirculatory hemodynamics between intravenous (IV) adenosine hyperemia versus physical exercise stress in patients with CCS and coronary stenosis. METHODS: Twenty-three patients (mean age, 60.6 ± 8.1 years) with CCS and single-vessel coronary stenosis underwent cardiac catheterization. Continuous trans-stenotic coronary pressure-flow measurements were performed during: i) IV adenosine hyperemia, and ii) physical exercise using a catheter-table-mounted supine ergometer. Systemic, coronary and microcirculatory hemodynamic responses were compared between IV adenosine and exercise stimuli. RESULTS: Mean stenosis diameter was 74.6% ± 10.4. Median (interquartile range) FFR was 0.54 (0.44-0.72). At adenosine hyperemia versus exercise stress, mean aortic pressure (Pa, 91 ± 16 mmHg vs 99 ± 15 mmHg, p < 0.0001), distal coronary pressure (Pd, 58 ± 21 mmHg vs 69 ± 24 mmHg, p < 0.0001), trans-stenotic pressure ratio (Pd/Pa, 0.63 ± 0.18 vs 0.69 ± 0.19, p < 0.0001), microvascular resistance (MR, 2.9 ± 2.2 mmHg.cm-1.sec-1 vs 4.2 ± 1.7 mmHg.cm-1.sec-1, p = 0.001), heart rate (HR, 80 ± 15 bpm vs 85 ± 21 bpm, p = 0.02) and rate-pressure product (RPP, 7522 ± 2335 vs 9077 ± 3200, p = 0.0001) were all lower. Conversely, coronary flow velocity (APV, 23.7 ± 9.5 cm/s vs 18.5 ± 6.8 cm/s, p = 0.02) was higher. Additionally, temporal changes in Pa, Pd, Pd/Pa, MR, HR, RPP and APV during IV adenosine hyperemia versus exercise were all significantly different (p < 0.05 for all). CONCLUSIONS: In patients with CCS and coronary stenosis, invasive hemodynamic responses differed markedly between IV adenosine hyperemia versus physical exercise stress. These differences were observed across systemic, coronary and microcirculatory hemodynamics.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34366296

RESUMO

Percutaneous closure of paravalvar leaks (PVLs) was once only performed in extreme or non-surgical risk cases not suitable for redo-surgery with tissue or mechanical valves. This technique is now the treatment of choice with long term outcomes that are better than redo operations.123 As interventionalists become more familiar with using PVL devices, more off label device use has been reported in non-surgical cases involving complex native mitral valve regurgitation (NVMR). In this review, we appraise the literature regarding percutaneous treatment of paravalvar leaks and more recently esoteric off label use. We also describe two recent challenging cases where percutaneous devices were used to treat severe leaks that developed as a sequela of previous infective endocarditis. We also provide specific recommendations regarding periprocedural strategy and focus on the importance of device choice to provide an optimal outcome.

10.
Braz J Biol ; 82: e237040, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34105668

RESUMO

This investigation presents the food and feeding activity of and endangered riverine catfish Rita rita, during February 2017-January 2018. A total of 225 fish individuals was analyzed for stomach contents by characterizing the dominant food items and morphometric features. The results divulged ten major food items consumed, preferably fish scales and eggs, teleost fishes, copepods, cladocerans, rotifers, and mollusks. Total length and body weight of fish varied between 9-34 cm (20.53 ± 6.90 cm) and 10-400 g (9125.94 ± 102.07 g), respectively. The index of relative importance (IRI%) showed the importance of rotifers over the other food items. Morisita's index of diet overlap indicated seasonal variations in catfish diets with summer and monsoon displaying the least overlap, while maximum overlap during monsoon and winter seasons. The non-metric multidimensional scaling (nMDS) indicated the close association between the food items available during summer and winter seasons with a significant difference among the seasons (ANOSIM, R = 0.638, P = 0.013). Levin's niche breadth index arranged in the order of 0.88>0.81>0.78>0.63>0.43 for the size classes of V, IV, III, II and I, respectively. The PCA explained 95.39% of the total variance among the food items and fish size groups. Small-sized fish individuals displayed a greater correlation with food items suitable for their mouth size. In conclusion, the variety and frequency of food items recorded indicated considerable feeding plasticity and opportunistic feeding behavior with a shift from carnivorous to omnivorous feeding nature. This study could render useful information on the food and feeding habits of R. rita and provide background for preparing its diet for future aquaculture practices.


Assuntos
Peixes-Gato , Animais , Comportamento Alimentar , Conteúdo Gastrointestinal , Hábitos , Humanos , Estações do Ano
12.
J Am Coll Cardiol ; 77(20): 2466-2476, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34016259

RESUMO

BACKGROUND: Published data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear. OBJECTIVES: The purpose of this study was to report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ACS patients and compare these with pre-COVID-19 cohorts. METHODS: From March 1, 2020 to July 31, 2020, data from 55 international centers were entered into a prospective, COVID-ACS Registry. Patients were COVID-19 positive (or had a high index of clinical suspicion) and underwent invasive coronary angiography for suspected ACS. Outcomes were in-hospital major cardiovascular events (all-cause mortality, re-myocardial infarction, heart failure, stroke, unplanned revascularization, or stent thrombosis). Results were compared with national pre-COVID-19 databases (MINAP [Myocardial Ischaemia National Audit Project] 2019 and BCIS [British Cardiovascular Intervention Society] 2018 to 2019). RESULTS: In 144 ST-segment elevation myocardial infarction (STEMI) and 121 non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients, symptom-to-admission times were significantly prolonged (COVID-STEMI vs. BCIS: median 339.0 min vs. 173.0 min; p < 0.001; COVID NSTE-ACS vs. MINAP: 417.0 min vs. 295.0 min; p = 0.012). Mortality in COVID-ACS patients was significantly higher than BCIS/MINAP control subjects in both subgroups (COVID-STEMI: 22.9% vs. 5.7%; p < 0.001; COVID NSTE-ACS: 6.6% vs. 1.2%; p < 0.001), which remained following multivariate propensity analysis adjusting for comorbidities (STEMI subgroup odds ratio: 3.33 [95% confidence interval: 2.04 to 5.42]). Cardiogenic shock occurred in 20.1% of COVID-STEMI patients versus 8.7% of BCIS patients (p < 0.001). CONCLUSIONS: In this multicenter international registry, COVID-19-positive ACS patients presented later and had increased in-hospital mortality compared with a pre-COVID-19 ACS population. Excessive rates of and mortality from cardiogenic shock were major contributors to the worse outcomes in COVID-19 positive STEMI patients.


Assuntos
Síndrome Coronariana Aguda/virologia , COVID-19/complicações , Sistema de Registros , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/mortalidade , Idoso , Angiografia Coronária , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade
13.
Org Biomol Chem ; 19(13): 2949-2958, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33725086

RESUMO

Electrophilic borylation of indoles with BX3 (X = Cl or Br) using directing groups installed at N1 can proceed at the C2 or the C7 position. The six membered heterocycle directing groups utilised herein, pyridines and pyrimidine, result in indole C2 borylation being the dominant outcome (in the absence of a C2-substituent). In contrast, C7 borylation was achieved using five membered heterocycle directing groups, such as thiazole and benzoxazole. Calculations on the borylation of indole substituted with a five (thiazole) and a six (pyrimidine) membered heterocycle directing group indicated that borylation proceeds via borenium cations with arenium cation formation having the highest barrier in both cases. The C7 borylated isomer was calculated to be the thermodynamically favoured product with both five and six membered heterocycle directing groups, but for pyrimidine directed indole borylation the C2 product was calculated to be the kinetic product. This is in contrast to thiazole directed indole borylation with BCl3 where the C7 borylated isomer is the kinetic product too. Thus, heterocycle ring size is a useful way to control C2 vs. C7 selectivity in N-heterocycle directed indole C-H borylation.

14.
Leukemia ; 35(8): 2274-2284, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33526858

RESUMO

Despite significant progress over the last few decades in the treatment of acute myeloid leukemia (AML), there still remains a major unmet medical need for this disease. Immunotherapy approaches for redirecting pan CD3+ T cells to target leukemia blasts have shown limited efficacy in clinical trials and often accompanied with severe toxicity in AML patients. We designed an alternative engager molecule (Anti-TRGV9/anti-CD123), a bispecific antibody that can simultaneously bind to the Vγ9 chain of the Vγ9Vδ2+ γδ T cell receptor and to AML target antigen, CD123, to selectively recruit Vγ9+ γδ T cells rather than pan T cells to target AML blasts. Our results suggest that prototypic bispecific antibodies (a) selectively activate Vγ9+ γδ T cells as judged by CD69 and CD25 surface expression, and intracellular Granzyme B expression, (b) selectively recruit Vγ9+ γδ T cells into cell-cell conjugate formation of γδ T cells with tumor cells indicating selective and effective engagement of effector and target tumor cells, and (c) mediate γδ T cell cytotoxicity (in vitro and in vivo) against tumor antigen-expressing cells. Collectively, these findings suggest that selectively redirecting Vγ9+ γδ T cells to target AML blasts has a potential for immunotherapy for AML patients and favors further exploration of this concept.


Assuntos
Anticorpos Biespecíficos/imunologia , Antineoplásicos Imunológicos/farmacologia , Imunoterapia/métodos , Leucemia Experimental/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Animais , Citotoxicidade Imunológica , Humanos , Leucemia Experimental/imunologia , Leucemia Experimental/patologia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Catheter Cardiovasc Interv ; 98(3): E444-E452, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33502784

RESUMO

OBJECTIVES: To determine whether a permanent pacemaker (PPM) in situ can enhance survival after transcatheter aortic valve implantation (TAVI), in a predominantly inoperable or high risk cohort. BACKGROUND: New conduction disturbances are the most frequent complication of TAVI, often necessitating PPM implantation before hospital discharge. METHODS: We performed an observational cohort analysis of the UK TAVI registry (2007-2015). Primary and secondary endpoints were 30-day post-discharge all-cause mortality and long-term survival, respectively. RESULTS: Of 8,651 procedures, 6,815 complete datasets were analyzed. A PPM at hospital discharge, irrespective of when implantation occurred (PPM 1.68% [22/1309] vs. no PPM 1.47% [81/5506], odds ratio [OR] 1.14, 95% confidence interval [CI] 0.71-1.84; p = .58), or a PPM implanted peri- or post-TAVI only (PPM 1.44% [11/763] vs. no PPM 1.47% [81/5506], OR 0.98 [0.51-1.85]; p = .95) did not significantly reduce the primary endpoint. Patients with a PPM at discharge were older, male, had right bundle branch block at baseline, were more likely to have received a first-generation self-expandable prosthesis and had experienced more peri- and post-procedural complications including bailout valve-in-valve rescue, bleeding and acute kidney injury. A Cox proportional hazards model demonstrated significantly reduced long-term survival in all those with a PPM, irrespective of implantation timing (hazard ratio [HR] 1.14 [1.02-1.26]; p = .019) and those receiving a PPM only at the time of TAVI (HR 1.15 [1.02-1.31]; p = .032). The reasons underlying this observation warrant further investigation. CONCLUSIONS: A PPM did not confer a survival advantage in the first 30 days after hospital discharge following TAVI.

16.
Br J Cancer ; 124(6): 1037-1048, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33469153

RESUMO

The development of bispecific antibodies that redirect the cytotoxic activity of CD3+ T cells to tumours is a promising immunotherapeutic strategy for the treatment of haematological malignancies and solid cancers. Since the landmark FDA approval at the end of 2014 of the anti-CD3 × anti-CD19 bispecific antibody blinatumomab (Blincyto®) for the treatment of relapsed/refractory B-cell acute lymphoblastic leukaemia, ~100 clinical trials investigating the safety and efficacy of CD3+ bispecific T-cell redirectors for cancer have been initiated. However, despite early success, numerous challenges pertaining to CD3+ T-cell redirection in the context of cancer exist, including the recruitment of counterproductive CD3+ T-cell subsets, the release of systemic cytokines, the expansion of immune checkpoint molecules, the presence of an immunosuppressive tumour microenvironment, tumour antigen loss/escape, on-target off-tumour toxicity and suboptimal potency. The aim of the present review is to discuss novel approaches to overcome the key challenges associated with CD3+ bispecific T-cell redirection in order to achieve an optimal balance of anti-tumour activity and safety.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Antígenos CD19/imunologia , Antineoplásicos/uso terapêutico , Complexo CD3/imunologia , Neoplasias/tratamento farmacológico , Microambiente Tumoral/imunologia , Animais , Humanos , Neoplasias/imunologia , Neoplasias/patologia
17.
J Am Heart Assoc ; 10(3): e017381, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33496201

RESUMO

Background In stable coronary artery disease, medications are used for 2 purposes: cardiovascular risk reduction and symptom improvement. In clinical trials and clinical practice, medication use is often not optimal. The ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) trial was the first placebo-controlled trial of percutaneous coronary intervention. A key component of the ORBITA trial design was the inclusion of a medical optimization phase, aimed at ensuring that all patients were treated with guideline-directed truly optimal medical therapy. In this study, we report the medical therapy that was achieved. Methods and Results After enrollment into the ORBITA trial, all 200 patients entered a 6-week period of intensive medical therapy optimization, with initiation and uptitration of risk reduction and antianginal therapy. At the prerandomization stage, the median number of antianginals established was 3 (interquartile range, 2-4). A total of 195 patients (97.5%) reached the prespecified target of ≥2 antianginals; 136 (68.0%) did not stop any antianginals because of adverse effects, and the median number of antianginals stopped for adverse effects per patient was 0 (interquartile range, 0-1). Amlodipine and bisoprolol were well tolerated (stopped for adverse effects in 4/175 [2.3%] and 9/167 [5.4%], respectively). Ranolazine and ivabradine were also well tolerated (stopped for adverse effects in 1/20 [5.0%] and 1/18 [5.6%], respectively). Isosorbide mononitrate and nicorandil were stopped for adverse effects in 36 of 172 (20.9%) and 32 of 141 (22.7%) of patients, respectively. Statins were well tolerated and taken by 191 of 200 (95.5%) patients. Conclusions In the 12-week ORBITA trial period, medical therapy was successfully optimized and well tolerated, with few drug adverse effects leading to therapy cessation. Truly optimal medical therapy can be achieved in clinical trials, and translating this into longer-term clinical practice should be a focus of future study. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02062593.


Assuntos
Anlodipino/uso terapêutico , Bisoprolol/administração & dosagem , Doença da Artéria Coronariana/terapia , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Dinitrato de Isossorbida/análogos & derivados , Nicorandil/administração & dosagem , Ranolazina/administração & dosagem , Fármacos Cardiovasculares/administração & dosagem , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Humanos , Dinitrato de Isossorbida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Resultado do Tratamento , Vasodilatadores/administração & dosagem
18.
Trends Biotechnol ; 39(3): 298-310, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32807530

RESUMO

Intracellular delivery of therapeutic antibodies is highly desirable but remains a challenge for biomedical research and the pharmaceutical industry. Approximately two-thirds of disease-associated targets are found inside the cell. Difficulty blocking these targets with available drugs creates a need for technology to deliver highly specific therapeutic antibodies intracellularly. Historically, antibodies have not been believed to traverse the cell membrane and neutralize intracellular targets. Emerging evidence has revealed that anti-DNA autoantibodies found in systemic lupus erythematosus (SLE) patients can penetrate inside the cell. Harnessing this technology has the potential to accelerate the development of drugs against intracellular targets. Here, we dissect the mechanisms of the intracellular localization of SLE antibodies and discuss how to apply these insights to engineer successful cell-penetrating antibody drugs.

19.
Catheter Cardiovasc Interv ; 97(3): 516-526, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32865860

RESUMO

OBJECTIVE: To evaluate the incidence, predictors and outcomes of female patients with patient-prosthesis mismatch (PPM) following transcatheter aortic valve intervention (TAVI) for severe aortic stenosis (AS). BACKGROUND: Female AS TAVI recipients have a significantly lower mortality than surgical aortic valve replacement (SAVR) recipients, which could be attributed to the potentially lower PPM rates. TAVI has been associated with lower rates of PPM compared to SAVR. PPM in females post TAVI has not been investigated to date. METHODS: The WIN-TAVI (Women's INternational Transcatheter Aortic Valve Implantation) registry is a multicenter registry of women undergoing TAVR for severe symptomatic AS. Two hundred and fifty patients with detailed periprocedural and follow-up echocardiographic investigations were included in the WIN-TAVI echocardiographic sub-study. PPM was defined as per European guidelines stratified by the presence of obesity. RESULTS: The incidence of PPM in our population was 32.8%. Patients with PPM had significantly higher BMI (27.4 ± 6.1 vs. 25.2 ± 5.0, p = .002), smaller sized valves implanted (percentage of TAVI ≤23 mm 61% vs. 29.2%, PPM vs. no PPM, p < .001) and were more often treated with balloon expandable valves (48.3 vs. 32.5%, p < .001) rather than self expanding ones (26.3 vs. 52.8%, <.001). BMI (OR = 1.08; 95%CI 1.02-1.14, p = .011) and valve size ≤23 mm (OR = 3.00 95%CI 1.14-7.94, p = .027) were the only independent predictors of PPM. There was no significant interaction between valve size and valve type (p = .203). No significant differences were observed in 1-year mortality or major adverse cardiovascular events. CONCLUSIONS: PPM in females undergoing TAVI occurs in one third of patients. BMI and valve size ≤23 mm are independent predictors. Larger registries are required to determine the impact of PPM on future clinical outcomes.

20.
Cardiovasc Revasc Med ; 22: 3-7, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32553849

RESUMO

INTRODUCTION: We aimed to investigate the optimal timing of invasive coronary angiography and subsequent intervention in non-ST-segment elevation acute myocardial infarction (NSTEMI) patients. METHODS: We examined the impact of early (≤24 h) versus delayed (>24 h) intervention in a large observational cohort of 20,882 consecutive NSTEMI patients treated with PCI between 2005 and 2015 at 8 tertiary cardiac centers in London (UK) using Cox-regression analysis and propensity matching. RESULTS: Mean age was 64.5 ± 12.7 years and 26.1% were females. A quarter (27.6%), were treated within 24 h. Patients treated within 24 h were slightly younger (62.8 ± 12.8 vs. 65.2 ± 12.6, p < 0.001), most commonly male (76% vs. 72.9%, p < 0.001) and were more frequently ventilated (2.3% vs. 1.4%, p < 0.001) and in cardiogenic shock (3.6% vs. 1.4%, p < 0.001) with dynamic changes on their ECG (84.5% vs. 76.1% p < 0.001). At a median follow up of 4.2 years (interquartile range 1.8 to 7) 17.7% of patients had died. Estimated 5-year survival in patients treated within 24 h was 84.6% vs. 81% for those treated >24 h following their presentation (p < 0.001). This survival benefit remained following adjustment for confounders; HR(delayed vs. early management) 1.11 (95%CI 1.003 to 1.23, p = 0.046). In the propensity matched cohort of 4356 patients in each group, there remained a trend for higher survival in the early intervention group (p = 0.061). CONCLUSIONS: Notwithstanding the limitations of the retrospective design, this real-world cohort of NSTEMI patients suggests that an early intervention (≤24 h) may improve mid-term survival.

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