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1.
Trials ; 22(1): 42, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430924

RESUMO

OBJECTIVES: As of December, 1st, 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, resulted in more than 1 472 917 deaths worldwide and death toll is still increasing exponentially. Many COVID-19 infected people are asymptomatic or experience moderate symptoms and recover without medical intervention. However, older people and those with comorbid hypertension, diabetes, obesity, or heart disease are at higher risk of mortality. Because current therapeutic options for COVID-19 patients are limited specifically for this elderly population at risk, Biophytis is developing BIO101 (20-hydroxyecdysone, a Mas receptor activator) as a new treatment option for managing patients with SARS-CoV-2 infection at the severe stage. The angiotensin converting enzyme 2 (ACE2) serves as a receptor for SARS-CoV-2. Interaction between ACE2 and SARS-CoV2 spike protein seems to alter the function of ACE2, a key player in the renin-angiotensin system (RAS). The clinical picture of COVID-19 includes acute respiratory distress syndrome (ARDS), cardiomyopathy, multiorgan dysfunction and shock, all of which might result from an imbalance of the RAS. We propose that RAS balance could be restored in COVID-19 patients through MasR activation downstream of ACE2 activity, with 20-hydroxyecdysone (BIO101) a non-peptidic Mas receptor (MasR) activator. Indeed, MasR activation by 20-hydroxyecdysone harbours anti-inflammatory, anti-thrombotic, and anti-fibrotic properties. BIO101, a 97% pharmaceutical grade 20-hydroxyecdysone could then offer a new therapeutic option by improving the respiratory function and ultimately promoting survival in COVID-19 patients that develop severe forms of this devastating disease. Therefore, the objective of this COVA study is to evaluate the safety and efficacy of BIO101, whose active principle is 20-hydroxyecdysone, in COVID-19 patients with severe pneumonia. TRIAL DESIGN: Randomized, double-blind, placebo-controlled, multi-centre, group sequential and adaptive which will be conducted in 2 parts. Part 1: Ascertain the safety and tolerability of BIO101 and obtain preliminary indication of the activity of BIO101, in preventing respiratory deterioration in the target population Part 2: Re-assessment of the sample size needed for the confirmatory part 2 and confirmation of the effect of BIO101 observed in part 1 in the target population. The study is designed as group sequential to allow an efficient run-through, from obtaining an early indication of activity to a final confirmation. And adaptive - to allow accumulation of early data and adapt sample size in part 2 in order to inform the final design of the confirmatory part of the trial. PARTICIPANTS: Inclusion criteria 1. Age: 45 and above 2. A confirmed diagnosis of COVID-19 infection, within the last 14 days, prior to randomization, as determined by PCR or other approved commercial or public health assay, in a specimen as specified by the test used. 3. Hospitalized, in observation or planned to be hospitalized due to COVID-19 infection symptoms with anticipated hospitalization duration ≥3 days 4. With evidence of pneumonia based on all of the following: a. Clinical findings on a physical examination b. Respiratory symptoms developed within the past 7 days 5. With evidence of respiratory decompensation that started not more than 4 days before start of study medication and present at screening, meeting one of the following criteria, as assessed by healthcare staff: a. Tachypnea: ≥25 breaths per minute b. Arterial oxygen saturation ≤92% c. A special note should be made if there is suspicion of COVID-19-related myocarditis or pericarditis, as the presence of these is a stratification criterion 6. Without a significant deterioration in liver function tests: a. ALT and AST ≤ 5x upper limit of normal (ULN) b. Gamma-glutamyl transferase (GGT) ≤ 5x ULN c. Total bilirubin ≤ 5×ULN 7. Willing to participate and able to sign an informed consent form (ICF). Or, when relevant, a legally authorized representative (LAR) might sign the ICF on behalf of the study participant 8. Female participants should be: at least 5 years post-menopausal (i.e., persistent amenorrhea 5 years in the absence of an alternative medical cause) or surgically sterile; OR a. Have a negative urine pregnancy test at screening b. Be willing to use a contraceptive method as outlined in inclusion criterion 9 from screening to 30 days after last dose. 9. Male participants who are sexually active with a female partner must agree to the use of an effective method of birth control throughout the study and until 3 months after the last administration of the investigational product. (Note: medically acceptable methods of contraception that may be used by the participant and/or partner include combined oral contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine device, etonogestrel implant, each supplemented with a condom, as well as sterilization and vasectomy). 10. Female participants who are lactating must agree not to breastfeed during the study and up to 14 days after the intervention. 11. Male participants must agree not to donate sperm for the purpose of reproduction throughout the study and until 3 months after the last administration of the investigational product. 12. For France only: Being affiliated with a European Social Security. Exclusion criteria 1. Not needing or not willing to remain in a healthcare facility during the study 2. Moribund condition (death likely in days) or not expected to survive for >7 days - due to other and non-COVID-19 related conditions 3. Participant on invasive mechanical ventilation via an endotracheal tube, or extracorporeal membrane oxygenation (ECMO), or high-flow Oxygen (delivery of oxygen at a flow of ≥16 L/min.). 4. Participant is not able to take medications by mouth (as capsules or as a powder, mixed in water). 5. Disallowed concomitant medication: Consumption of any herbal products containing 20-hydroxyecdysone and derived from Leuzea carthamoides; Cyanotis vaga or Cyanotis arachnoidea is not allowed (e.g. performance enhancing agents). 6. Any known hypersensitivity to any of the ingredients, or excipients of the study medication, BIO101. 7. Renal disease requiring dialysis, or known renal insufficiency (eGFR≤30 mL/min/1.73 m2, based on Cockcroft & Gault formula). 8. In France only: a. Non-affiliation to compulsory French social security scheme (beneficiary or right-holder). b. Being under tutelage or legal guardianship. Participants will be recruited from approximately 30 clinical centres in Belgium, France, the UK, USA and Brazil. Maximum patients' participation in the study will last 28 days. Follow-up of participants discharged from hospital will be performed through post-intervention phone calls at 14 (± 2) and 60 (± 4) days. INTERVENTION AND COMPARATOR: Two treatment arms will be tested in this study: interventional arm 350 mg b.i.d. of BIO101 (AP 20-hydroxyecdysone) and placebo comparator arm 350 mg b.i.d of placebo. Administration of daily dose is the same throughout the whole treatment period. Participants will receive the study medication while hospitalized for up to 28 days or until a clinical endpoint is reached (i.e., 'negative' or 'positive' event). Participants who are officially discharged from hospital care will no longer receive study medication. MAIN OUTCOMES: Primary study endpoint: The proportion of participants with 'negative' events up to 28 days. 'Negative' events are defined as respiratory deterioration and all-cause mortality. For the purpose of this study, respiratory deterioration will be defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage). Requiring extracorporeal membrane oxygenation (ECMO). Requiring high-flow oxygen defined as delivery of oxygen at a flow of ≥16 L/min. Only if the primary endpoint is significant at the primary final analysis the following Key secondary endpoints will be tested in that order: Proportion of participants with events of respiratory failure at Day 28 Proportion of participants with 'positive' events at Day 28. Proportion of participants with events of all-cause mortality at Day 28 A 'positive' event is defined as the official discharge from hospital care by the department due to improvement in participant condition. Secondary and exploratory endpoints: In addition, a variety of functional measures and biomarkers (including the SpO2 / FiO2 ratio, viral load and markers related to inflammation, muscles, tissue and the RAS / MAS pathways) will also be collected. RANDOMIZATION: Randomization is performed using an IBM clinical development IWRS system during the baseline visit. Block-permuted randomization will be used to assign eligible participants in a 1:1 ratio. In part 1, randomization will be stratified by RAS pathway modulator use (yes/no) and co-morbidities (none vs. 1 and above). In Part 2, randomization will be stratified by centre, gender, RAS pathway modulator use (yes/no), co-morbidities (none vs. 1 and above), receiving Continuous Positive Airway Pressure/Bi-level Positive Airway Pressure (CPAP/BiPAP) at study entry (Yes/No) and suspicion of COVID-19 related myocarditis or pericarditis (present or not). BLINDING (MASKING): Participants, caregivers, and the study team assessing the outcomes are blinded to group assignment. All therapeutic units (TU), BIO101 b.i.d. or placebo b.i.d., cannot be distinguished in compliance with the double-blind process. An independent data-monitoring committee (DMC) will conduct 2 interim analyses. A first one based on the data from part 1 and a second from the data from parts 1 and 2. The first will inform about BIO101 safety, to allow the start of recruitment into part 2 followed by an analysis of the efficacydata, to obtain an indication of activity. The second interim analysis will inform about the sample size that will be required for part 2, in order to achieve adequate statistical power. Numbers to be randomised (sample size) Number of participants randomized: up to 465, in total Part 1: 50 (to obtain the proof of concept in COVID-19 patients). Part 2: 310, potentially increased by 50% (up to 465, based on interim analysis 2) (to confirm the effects of BIO101 observed in part 1). TRIAL STATUS: The current protocol Version is V 10.0, dated on 24.09.2020. The recruitment that started on September 1st 2020 is ongoing and is anticipated to finish for the whole study by March2021. TRIAL REGISTRATION: The trial was registered before trial start in trial registries: EudraCT , No. 2020-001498-63, registered May 18, 2020; and Clinicaltrials.gov, identifier NCT04472728 , registered July 15, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Tratamento Farmacológico da COVID-19 , Ecdisterona/uso terapêutico , Insuficiência Respiratória/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/fisiopatologia , Progressão da Doença , Método Duplo-Cego , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Hospitalização , Humanos , Hipóxia/fisiopatologia , Pessoa de Meia-Idade , Mortalidade , Oxigenoterapia/estatística & dados numéricos , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Coronavírus/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Sistema Renina-Angiotensina , Respiração Artificial/estatística & dados numéricos , Insuficiência Respiratória/fisiopatologia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/metabolismo , Taquipneia/fisiopatologia , Resultado do Tratamento
3.
Am J Physiol Heart Circ Physiol ; 315(2): H254-H261, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29652541

RESUMO

The incidence of neurological complications, including stroke and cognitive dysfunction, is elevated in patients with heart failure (HF) with reduced ejection fraction. We hypothesized that the cerebrovascular response to isometric handgrip (iHG) is altered in patients with HF. Adults with HF and healthy volunteers were included. Cerebral blood velocity (CBV; transcranial Doppler, middle cerebral artery) and arterial blood pressure (BP; Finometer) were continuously recorded supine for 6 min, corresponding to 1 min of baseline and 3 min of iHG exercise, at 30% maximum voluntary contraction, followed by 2 min of recovery. The resistance-area product was calculated from the instantaneous BP-CBV relationship. Dynamic cerebral autoregulation (dCA) was assessed with the time-varying autoregulation index estimated from the CBV step response derived by an autoregressive moving-average time-domain model. Forty patients with HF and 23 BP-matched healthy volunteers were studied. Median left ventricular ejection fraction was 38.5% (interquartile range: 0.075%) in the HF group. Compared with control subjects, patients with HF exhibited lower time-varying autoregulation index during iHG, indicating impaired dCA ( P < 0.025). During iHG, there were steep rises in CBV, BP, and heart rate in control subjects but with different temporal patterns in HF, which, together with the temporal evolution of resistance-area product, confirmed the disturbance in dCA in HF. Patients with HF were more likely to have impaired dCA during iHG compared with age-matched control subjects. Our results also suggest an impairment of myogenic, neurogenic, and metabolic control mechanisms in HF. The relationship between impaired dCA and neurological complications in patients with HF during exercise deserves further investigation. NEW & NOTEWORTHY Our findings provide the first direct evidence that cerebral blood flow regulatory mechanisms can be affected in patients with heart failure during isometric handgrip exercise. As a consequence, eventual blood pressure modulations are buffered less efficiently and metabolic demands may not be met during common daily activities. These deficits in cerebral autoregulation are compounded by limitations of the systemic response to isometric exercise, suggesting that patients with heart failure may be at greater risk for cerebral events during exercise.


Assuntos
Circulação Cerebrovascular , Força da Mão , Insuficiência Cardíaca/fisiopatologia , Idoso , Feminino , Hemodinâmica , Homeostase , Humanos , Contração Isométrica , Masculino , Pessoa de Meia-Idade
4.
Br J Anaesth ; 119(5): 900-907, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28981596

RESUMO

Background: Major abdominal oncology surgery is associated with substantial postoperative loss of functional capacity, and exercise may be an effective intervention to improve outcomes. The aim of this study was to assess efficacy, feasibility and safety of a supervised postoperative exercise programme. Methods: We performed a single-blind, parallel-arm, randomized trial in patients who underwent major abdominal oncology surgery in a tertiary university hospital. Patients were randomized to an early mobilization postoperative programme based on supervised aerobic exercise, resistance and flexibility training or to standard rehabilitation care. The primary outcome was inability to walk without human assistance at postoperative day 5 or hospital discharge. Results: A total of 108 patients were enrolled, 54 into the early mobilization programme group and 54 into the standard rehabilitation care group. The incidence of the primary outcome was nine (16.7%) and 21 (38.9%), respectively (P=0.01), with an absolute risk reduction of 22.2% [95% confidence interval (CI) 5.9-38.6] and a number needed to treat of 5 (95% CI 3-17). All patients in the intervention group were able to follow at least partially the exercise programme, although the performance among them was rather heterogeneous. There were no differences between groups regarding clinical outcomes or complications related to the exercises. Conclusions: An early postoperative mobilization programme based on supervised exercises seems to be safe and feasible and improves functional capacity in patients undergoing major elective abdominal oncology surgery. However, its impact on clinical outcomes is still unclear. Clinical trial registration: NCT01693172.


Assuntos
Neoplasias Abdominais/reabilitação , Neoplasias Abdominais/cirurgia , Terapia por Exercício/métodos , Tolerância ao Exercício , Avaliação de Programas e Projetos de Saúde/métodos , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Resultado do Tratamento
5.
Physiol Meas ; 38(7): 1349-1361, 2017 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-28333037

RESUMO

OBJECTIVE: Intra-aortic balloon pump (IABP) is commonly used as mechanical support after cardiac surgery or cardiac shock. Although its benefits for cardiac function have been well documented, its effects on cerebral circulation are still controversial. We hypothesized that transfer function analysis (TFA) and continuous estimates of dynamic cerebral autoregulation (CA) provide consistent results in the assessment of cerebral autoregulation in patients with IABP. APPROACH: Continuous recordings of blood pressure (BP, intra-arterial line), end-tidal CO2, heart rate and cerebral blood flow velocity (CBFV, transcranial Doppler) were obtained (i) 5 min with IABP ratio 1:3, (ii) 5 min, starting 1 min with the IABP-ON, and continuing for another 4 min without pump assistance (IABP-OFF). Autoregulation index (ARI) was estimated from the CBFV response to a step change in BP derived by TFA and as a function of time using an autoregressive moving-average model during removal of the device (ARI t ). Critical closing pressure and resistance area-product were also obtained. MAIN RESULTS: ARI with IABP-ON (4.3 ± 1.2) were not different from corresponding values at IABP-OFF (4.7 ± 1.4, p = 0.42). Removal of the balloon had no effect on ARI t , CBFV, BP, cerebral critical closing pressure or resistance area-product. SIGNIFICANCE: IABP does not disturb cerebral hemodynamics. TFA and continuous estimates of dynamic CA can be used to assess cerebral hemodynamics in patients with IABP. These findings have important implications for the design of studies of critically ill patients requiring the use of different invasive support devices.


Assuntos
Circulação Cerebrovascular , Hemodinâmica , Balão Intra-Aórtico/efeitos adversos , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade
6.
Am J Physiol Regul Integr Comp Physiol ; 312(1): R108-R113, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27927624

RESUMO

Patients with ischemic heart failure (iHF) have a high risk of neurological complications such as cognitive impairment and stroke. We hypothesized that iHF patients have a higher incidence of impaired dynamic cerebral autoregulation (dCA). Adult patients with iHF and healthy volunteers were included. Cerebral blood flow velocity (CBFV, transcranial Doppler, middle cerebral artery), end-tidal CO2 (capnography), and arterial blood pressure (Finometer) were continuously recorded supine for 5 min at rest. Autoregulation index (ARI) was estimated from the CBFV step response derived by transfer function analysis using standard template curves. Fifty-two iHF patients and 54 age-, gender-, and BP-matched healthy volunteers were studied. Echocardiogram ejection fraction was 40 (20-45) % in iHF group. iHF patients compared with control subjects had reduced end-tidal CO2 (34.1 ± 3.7 vs. 38.3 ± 4.0 mmHg, P < 0.001) and lower ARI values (5.1 ± 1.6 vs. 5.9 ± 1.0, P = 0.012). ARI <4, suggestive of impaired CA, was more common in iHF patients (28.8 vs. 7.4%, P = 0.004). These results confirm that iHF patients are more likely to have impaired dCA compared with age-matched controls. The relationship between impaired dCA and neurological complications in iHF patients deserves further investigation.


Assuntos
Circulação Cerebrovascular , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/fisiopatologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Velocidade do Fluxo Sanguíneo , Feminino , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações
8.
Clin Microbiol Infect ; 22(4): 352-358, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26711434

RESUMO

This study aimed to describe severe infections with extensively drug-resistant Acinetobacter baumannii-calcoaceticus complex (XDR-ABC), as well as to investigate risk factors for mortality, in cancer patients. It was a retrospective study including all patients diagnosed with XDR-ABC bacteraemia during hospitalization in the intensive care unit of a cancer hospital between July 2009 and July 2013. Surveillance cultures were collected weekly during the study period, and clonality was analysed using pulsed field gel electrophoresis (PFGE). We analysed underlying diseases, oncology therapy, neutrophil counts, infection site and management of infection, in terms of their correlation with 30-day mortality. During the study period, 92 patients with XDR-ABC bacteraemia were identified, of whom 35 (38.0%) were patients with haematological malignancy. We identified XDR-ABC strains with four different profile patterns, 91.3% of patients harbouring the predominant PFGE type. Of the 92 patients with XDR-ABC bacteraemia, 66 (71.7%) had central line-associated bloodstream infections; infection occurred during neutropenia in 22 (23.9%); and 58 (63.0%) died before receiving the appropriate therapy. All patients were treated with polymyxin, which was used in combination therapy in 30 of them (32.4%). The 30-day mortality rate was 83.7%. Multivariate analysis revealed that septic shock at diagnosis of XDR-ABC infection was a risk factor for 30-day mortality; protective factors were receiving appropriate therapy and invasive device removal within the first 48 h. Among cancer patients, ineffective management of such infection increases the risk of death, more so than do features such as neutropenia and infection at the tumour site.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Neoplasias/complicações , Neutropenia , Sepse/microbiologia , Infecções por Acinetobacter/complicações , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/mortalidade , Acinetobacter baumannii/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/mortalidade , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
9.
Br J Anaesth ; 115(4): 511-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26385661

RESUMO

BACKGROUND: Guidelines support the use of a restrictive strategy in blood transfusion management in a variety of clinical settings. However, recent randomized controlled trials (RCTs) performed in the perioperative setting suggest a beneficial effect on survival of a liberal strategy. We aimed to assess the effect of liberal and restrictive blood transfusion strategies on mortality in perioperative and critically ill adult patients through a meta-analysis of RCTs. METHODS: We searched PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, Transfusion Evidence Library, and Google Scholar up to 27 March 2015, for RCTs performed in perioperative or critically ill adult patients, receiving a restrictive or liberal transfusion strategy, and reporting all-cause mortality. We used a fixed or random-effects model to calculate the odds ratio (OR) and 95% confidence interval (CI) for pooled data. We assessed heterogeneity using Cochrane's Q and I(2) tests. The primary outcome was all-cause mortality within 90-day follow-up. RESULTS: Patients in the perioperative period receiving a liberal transfusion strategy had lower all-cause mortality when compared with patients allocated to receive a restrictive transfusion strategy (OR 0.81; 95% CI 0.66‒1.00; P=0.05; I(2)=25%; Number needed to treat=97) with 7552 patients randomized in 17 trials. There was no difference in mortality among critically ill patients receiving a liberal transfusion strategy when compared with the restrictive transfusion strategy (OR 1.10; 95% CI 0.99‒1.23; P=0.07; I(2)=34%) with 3469 patients randomized in 10 trials. CONCLUSION: According to randomized published evidence, perioperative adult patients have an improved survival when receiving a liberal blood transfusion strategy.


Assuntos
Transfusão de Sangue/estatística & dados numéricos , Cuidados Críticos/métodos , Estado Terminal/mortalidade , Assistência Perioperatória/mortalidade , Assistência Perioperatória/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Cuidados Críticos/estatística & dados numéricos , Humanos , Assistência Perioperatória/estatística & dados numéricos , Análise de Sobrevida , Resultado do Tratamento
10.
Arq Bras Cardiol ; 103(6 Suppl 2): 1-126, 2014 Dec.
Artigo em Português | MEDLINE | ID: mdl-25591041
11.
Transplant Proc ; 44(8): 2483-5, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23026625

RESUMO

BACKGROUND: Organ transplant recipients with refractory rejection or intolerance to the prescribed immunosuppressant may respond to rescue therapy with tacrolimus. We sought to evaluate the clinical outcomes of children undergoing heart transplantation who required conversion from a cyclosporine-based, steroid-free therapy to a tacrolimus-based regimen. METHODS: We performed a prospective, observational, cohort study of 28 children who underwent conversion from cyclosporine-based, steroid-free therapy to a tacrolimus-based therapy for refractory or late rejection or intolerance to cyclosporine. RESULTS: There was complete resolution of refractory rejection episodes and adverse side effects in all patients. The incidence rate (×100) of rejection episodes before and after conversion was 7.98 and 2.11, respectively (P ≤ .0001). There was a 25% mortality rate in patients using tacrolimus after a mean period of 60 months after conversion. CONCLUSION: Tacrolimus is effective as rescue therapy for refractory rejection and is a therapeutic option for pediatric patients.


Assuntos
Ciclosporina/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Transplante de Coração/imunologia , Imunossupressores/uso terapêutico , Tacrolimo/uso terapêutico , Fatores Etários , Criança , Pré-Escolar , Ciclosporina/efeitos adversos , Substituição de Medicamentos , Quimioterapia Combinada , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Transplante de Coração/mortalidade , Humanos , Imunossupressores/efeitos adversos , Incidência , Estimativa de Kaplan-Meier , Estudos Prospectivos , Terapia de Salvação , Tacrolimo/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
12.
Acta Anaesthesiol Scand ; 56(6): 712-7, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22621427

RESUMO

BACKGROUND: There are no studies that describe the impact of the cumulative fluid balance on the outcomes of cancer patients admitted to intensive care units ICUs. The aim of our study was to evaluate the relationship between fluid balance and clinical outcomes in these patients. METHOD: One hundred twenty-two cancer patients were prospectively evaluated for survival during a 30-day period. Univariate (Chi-square, t-test, Mann-Whitney) and multiple logistic regression analyses were used to identify the admission parameters associated with mortality. RESULTS: The mean cumulative fluid balance was significantly higher in non-survivors than in survivors [1675 ml/24 h (471-2921) vs. 887 ml/24 h (104-557), P = 0.017]. We used the area under the curve and the intersection of the sensibility and specificity curves to define a cumulative fluid balance value of 1100 ml/24 h. This value was used in the univariate model. In the multivariate model, the following variables were significantly associated with mortality in cancer patients: the Acute Physiology and Chronic Health Evaluation II score at admission [Odds ratio (OR) 1.15; 95% confidence interval (CI) (1.05-1.26), P = 0.003], the Lung Injury Score at admission [OR 2.23; 95% CI (1.29-3.87), P = 0.004] and a positive fluid balance higher than 1100 ml/24 h at ICU [OR 5.14; 95% CI (1.45-18.24), P = 0.011]. CONCLUSION: A cumulative positive fluid balance higher than 1100 ml/24 h was independently associated with mortality in patients with cancer. These findings highlight the importance of improving the evaluation of these patients' volemic state and indicate that defined goals should be used to guide fluid therapy.


Assuntos
Estado Terminal/mortalidade , Neoplasias/mortalidade , Neoplasias/fisiopatologia , Equilíbrio Hidroeletrolítico/fisiologia , APACHE , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/fisiopatologia , Idoso , Área Sob a Curva , Feminino , Humanos , Intubação Intratraqueal , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/fisiopatologia , Valor Preditivo dos Testes , Respiração Artificial , Choque Séptico/etiologia , Choque Séptico/fisiopatologia , Sobrevida , Resultado do Tratamento , Vasoconstritores/uso terapêutico
13.
Minerva Anestesiol ; 78(4): 426-33, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22240618

RESUMO

BACKGROUND: Acute normovolemic hemodilution (ANH) is an alternative to blood transfusion in surgeries involving blood loss. This experimental study was designed to evaluate whether pulse pressure variation (PPV) would be an adequate tool for monitoring changes in preload during ANH, as assessed by transesophageal echocardiography. METHODS: Twenty-one anesthetized and mechanically ventilated pigs were randomized into three groups: CTL (control), HES (hemodilution with 6% hydroxyethyl starch at a 1:1 ratio) or NS (hemodilution with saline 0.9% at a 3:1 ratio). Hemodilution was performed in animals of groups NS and HES in two stages, with target hematocrits 22% and 15%, achieved at 30-minute intervals. After two hours, 50% of the blood volume withdrawn was transfused and animals were monitored for another hour. Statistical analysis was based on ANOVA for repeated measures followed by multiple comparison test (P<0.05). Pearson's correlations were performed between changes in left ventricular end-diastolic volume (LVEDV) and PPV, central venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP). RESULTS: Group NS received a significantly greater amount of fluids during ANH (NS, 900 ± 168 mL vs. HES, 200 ± 50 mL, P<0.05) and presented greater urine output (NS, 2643 ± 1097 mL vs. HES, 641 ± 338 mL, P<0.001). Significant decreases in LVEDV were observed in group NS from completion of ANH until transfusion. In group HES, only increases in LVEDV were observed, at the end of ANH and at transfusion. Such changes in LVEDV (∆LVEDV) were better reflected by changes in PPV (∆PPV, R=-0.62) than changes in CVP (∆CVP, R=0.32) or in PAOP (∆PAOP, R=0.42, respectively). CONCLUSION: Changes in preload during ANH were detected by changes in PPV. ∆PPV was superior to ∆PAOP and ∆CVP to this end.


Assuntos
Pressão Sanguínea/fisiologia , Volume Sanguíneo/fisiologia , Hemodiluição/métodos , Animais , Superfície Corporal , Peso Corporal/fisiologia , Pressão Venosa Central/fisiologia , Coloides/uso terapêutico , Soluções Cristaloides , Ecocardiografia Transesofagiana , Coração/fisiologia , Hemodinâmica/fisiologia , Soluções Isotônicas/uso terapêutico , Substitutos do Plasma/uso terapêutico , Artéria Pulmonar/fisiologia , Suínos
14.
Ann Oncol ; 21(12): 2333-2341, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20511340

RESUMO

BACKGROUND: The natural history and consequences of severe H1N1 influenza infection among cancer patients are not yet fully characterized. We describe eight cases of H1N1 infection in cancer patients admitted to the intensive care unit of a referral cancer center. PATIENTS AND METHODS: Clinical data from all patients admitted with acute respiratory failure due to novel viral H1N1 infection were reviewed. Lung tissue was submitted for viral and bacteriological analyses by real-time RT-PCR, and autopsy was conducted on all patients who died. RESULTS: Eight patients were admitted, with ages ranging from 55 to 65 years old. There were five patients with solid organ tumors (62.5%) and three with hematological malignancies (37.5%). Five patients required mechanical ventilation and all died. Four patients had bacterial bronchopneumonia. All deaths occurred due to multiple organ failure. A milder form of lung disease was present in the three cases who survived. Lung tissue analysis was performed in all patients and showed diffuse alveolar damage in most patients. Other lung findings were necrotizing bronchiolitis or extensive hemorrhage. CONCLUSIONS: H1N1 viral infection in patients with cancer can cause severe illness, resulting in acute respiratory distress syndrome and death. More data are needed to identify predictors of unfavorable evolution in these patients.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana/complicações , Neoplasias/complicações , Idoso , Autopsia , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/diagnóstico por imagem , Influenza Humana/mortalidade , Influenza Humana/patologia , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/patologia , Neoplasias/diagnóstico por imagem , Neoplasias/mortalidade , Neoplasias/patologia , Radiografia , Respiração Artificial , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença
15.
Rev Soc Bras Med Trop ; 33(5): 451-64, 2000.
Artigo em Português | MEDLINE | ID: mdl-11064582

RESUMO

Gonorrhea is a common bacterial infection caused by Neisseria gonorrhoeae, a Gram-negative diplococcus that is transmitted almost exclusively by sexual contact or perinatally. It primarily affects the mucous membranes of the lower genital tract and less frequently those of the rectum, oropharynx, and conjunctivae. Ascending genital infection in women leads to the predominant complication, acute salpingitis, one of the most common causes of female infertility in the world. Since the 1990s, a remarkable surge of information ensued regarding the pathogenesis of gonorrhea and its agent. Gonorrhea has proven difficult to control in most populations and remains a prime example of the influence that social, behavioral, and demographic factors can have on the epidemiology of an infectious disease. The management of gonorrhea and other sexually transmitted infections requires both treatment of the patient as an individual and of his or her sexual partner(s) as a public health measure to interrupt the onward spread of infection and prevent long-term complications.


Assuntos
Gonorreia , Feminino , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Gonorreia/etiologia , Humanos , Masculino , Saúde Pública
16.
Pain ; 84(2-3): 397-405, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10666546

RESUMO

The role of ECM-degrading proteinases in normal developmental processes and in pathological conditions is extensively studied. However, few reports describe the role ECM-degrading proteinases play in modulating hyperalgesia. The goal of this study is to describe the regulation of gelatinases during endotoxin mediated local inflammation, induced by intra plantar endotoxin (ET; 1.25 microg/50 microl) injection in Balb/c mice, and to correlate that with hyperalgesia. ET injections induced hyperalgesia, as determined by hot plate and paw pressure tests, which peaked by 24 h and recovered by 48 h post-injection. Contralateral paw of ET injected mice and saline injected paws in control mice elicited no hyperalgesia. Zymography showed that ET and saline injected paws elicited increased gelatinase activity by 9 h after injection. However, only the former maintained high levels of expression of a 90 kD gelatinase up to at least 96 h post ET injection, while in the latter gelatinase expression was down regulated by 24 h. Interestingly, the 90-kD gelatinase was upregulated in the contralateral paw of the ET-injected mice beyond 48 h post injection. Saline injection in that paw, during a time when gelatinases are upregulated, induced hyperalgesia. Intraperitoneal injection of either ZnCl(2) (100 microM), thymulin (5 microg/100 microl), or morphine (2 mg/kg/100 microl) reversed the ET-induced hyperalgesia and suppressed gelatinase activity. Furthermore, intraperitoneal injection of MPI, an ECM-degrading proteinase inhibitor, reversed ET induced hyperalgesia. Taken together, the above suggests that a functional interplay exists between gelatinase upregulation triggered by ET injections and hyperalgesia. The exact mechanism underlying such correlation remains to be determined.


Assuntos
Gelatinases/fisiologia , Membro Posterior/fisiopatologia , Hiperalgesia/fisiopatologia , Dor/fisiopatologia , Animais , Endotoxinas , Inibidores Enzimáticos/farmacologia , Membro Posterior/enzimologia , Temperatura Alta , Inflamação/enzimologia , Inflamação/fisiopatologia , Masculino , Metaloendopeptidases/antagonistas & inibidores , Camundongos , Camundongos Endogâmicos BALB C , Dor/enzimologia , Estimulação Física , Cloreto de Sódio , Fator Tímico Circulante/farmacologia , Zinco/farmacologia
17.
Obstet Gynecol ; 82(4 Pt 2 Suppl): 642-4, 1993 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8377997

RESUMO

BACKGROUND: Tamoxifen has been used in the adjuvant treatment of breast cancer because of its antiestrogenic effects. However, recent reports have shown it to have estrogenic effects as well. The purpose of this report is to describe a potential association between tamoxifen therapy and endometriosis. CASE: A 50-year-old postmenopausal woman who had received 2 years of adjuvant tamoxifen therapy for breast carcinoma developed extensive tumor-like endometriosis necessitating extensive pelvic and intestinal surgery. CONCLUSION: This case report highlights the need for obstetricians and gynecologists to be familiar with the actions of tamoxifen and its potential complications.


Assuntos
Endometriose/induzido quimicamente , Neoplasias Intestinais/induzido quimicamente , Neoplasias Pélvicas/induzido quimicamente , Tamoxifeno/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Endometriose/diagnóstico , Feminino , Humanos , Neoplasias Intestinais/diagnóstico , Pessoa de Meia-Idade , Neoplasias Pélvicas/diagnóstico , Tamoxifeno/uso terapêutico
18.
J Med Liban ; 40(4): 194-7, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1339906

RESUMO

In order to study the behaviour of rectal cancer in our country, we have reviewed our experience at AUBMC over a 10-year period. We had 82 patients with rectal cancer, 36 males and 46 females, out of which 69 patients underwent surgical resection. Epidemiologically we have a significantly higher incidence of rectal cancer among females in contrast to western countries. Our operative results with respect to morbidity, mortality, recurrence and survival are discussed and compared to the literature.


Assuntos
Recidiva Local de Neoplasia , Neoplasias Retais/cirurgia , Centros Médicos Acadêmicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica/instrumentação , Anastomose Cirúrgica/métodos , Feminino , Seguimentos , Humanos , Incidência , Líbano/epidemiologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/epidemiologia , Neoplasias Retais/patologia , Fatores Sexuais , Grampeadores Cirúrgicos , Taxa de Sobrevida
19.
J Comp Pathol ; 101(1): 39-52, 1989 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2677067

RESUMO

Six juvenile green turtles (Chelonia mydas) from the Indian River Lagoon System, Florida, U.S.A., with multiple cutaneous fibropapillomas, were kept in isolation and examined over a 6-month period. Histologically, the fibropapillomas consisted of a slightly to moderately hyperplastic epidermis overlying a thickened hypercellular dermis. In the earliest lesions, ballooning degeneration was present predominantly in the stratum basale where rete ridges extended into the dermis; aggregates of mixed inflammatory cells were present around dermal vessels. As the lesions matured, they developed an arborizing, papillary pattern. More mature lesions had a less verrucous, often ulcerated surface, with the dermis composed primarily of large collagenous fascicles and relatively few fibroblasts. While numerous trematode eggs were present within dermal capillaries of a histologically similar biopsy specimen from an Hawaiian green turtle, no trematode eggs were observed in any of 28 biopsies examined from the six Florida green turtles in this study. Low stringency Southern blot hybridization and a reverse Southern blot failed to demonstrate papillomavirus DNA in any of the samples extracted. Ultrastructural evaluation of the earliest lesions demonstrated membrane-bound intracytoplasmic vacuoles within epidermal cells in the stratum basale. Similar vacuoles were also observed in the epidermal intercellular spaces and within the dermis. Occasionally, particles with electron-dense centres and measuring 155 to 190 nm were observed in these vacuoles.


Assuntos
Epiderme/patologia , Tartarugas/fisiologia , Animais , Southern Blotting , Epiderme/metabolismo , Epiderme/ultraestrutura , Hiperplasia/etiologia , Hiperplasia/patologia , Hiperplasia/veterinária , Técnicas Imunoenzimáticas , Microscopia Eletrônica
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