Optimal treatment sequencing of abiraterone acetate plus prednisone and enzalutamide in patients with castration-resistant metastatic prostate cancer: A systematic review and meta-analysis.

PURPOSE: To evaluate the impact of the hormonal treatment sequencing including abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) in mCRPC, and determine which sequence provides more benefits for patients. METHODS: Studies published in English between 1 January 2013 and 30 September 2017 were identified in PubMed and EMBASE electronic databases. Studies assessing the efficacy of treatment sequences, based on AAP and ENZ, in mCRPC patients, were eligible for analysis. RESULTS: Seventeen studies met the inclusion criteria. Two assessed both treatment sequences AAP â†’ ENZ and ENZ â†’ AAP; it was found that sequence of AAP â†’ ENZ showed a statistically significantly longer PSA-PFS than the observed in ENZ â†’ AAP (pooled HR: 0,54; 95% CI; 0,36-0,82; p < 0,05). The nine studies analysing Doc â†’ AAP â†’ ENZ sequence, revealed favourable results in terms of PFS. The 5 studies which analysed AAP â†’ ENZ sequence, show a decrease in PSA levels ≥ 50% in 11-41% of patients treated with enzalutamide after previous treatment with AAP. In the two studies that analysed the Doc â†’ ENZ â†’ AAP sequence, PSA response rates were much lower than those reported with Doc â†’ AAP â†’ ENZ, with decreases in PSA ≥ 30 of 3-18% and PSA ≥ 50 of 8-11%. CONCLUSION: Significant clinical efficacy of AAP administered as the first-line treatment in mCRPC patients followed by enzalutamide, delaying disease progression, compared with the ENZ â†’ AAP sequence. However, more studies and randomized trials are needed, to validate the best treatment sequencing.

Surgical Ligation Versus Percutaneous Closure of Patent Ductus Arteriosus in Very Low-Weight Preterm Infants: Which are the Real Benefits of the Percutaneous Approach?

Percutaneous treatment of patent ductus arteriosus (PDA) in extreme premature infants is technically difficult, and therefore, often not consider as an alternative to surgery. The main objective of our work was to compare respiratory status prior and post ductal closure and morbi-mortality, in our series of preterm infants with percutaneous PDA closure versus surgical ligation in the same time-period. Retrospective review of all premature infants submitted to percutaneous and surgical PDA closure from January 2011 to December 2016. All the antenatal, perinatal, and postnatal characteristics were collected. The main outcome was the assessment of the pulmonary status before and after ductal closure using a pulmonary score. Secondary outcomes included moderate-severe disability in neurodevelopment, death before discharge, moderate-severe chronic lung disease, and morbidity at discharge. 25 patients with a mean weight of 1330 g (± 280) underwent percutaneous closure of PDA with ADO-II-AS, and a total of 53 underwent surgical ligation. 28/53 with similar gestational age, birth weight, and procedure weight to those in the percutaneous group, were selected to perform the comparative study. Ductal closure (percutaneous and surgical) resulted in improved respiratory status. However, percutaneous group achieved a fastest respiratory improvement, than surgical group. The surgical closure group associated higher morbidity among survivors (HIV, number of sepsis, need, and duration of inotropics post-interventionism). The incidence of recurrent laryngeal nerve palsy among the surgical group was 17%. Percutaneous closure of PDA in carefully selected low-weight preterm infants is a safe and reliable alternative to surgical ligation.

[Clinical effect of mivacurium in morbidly obese patients]. / Efecto clínico del mivacurio en pacientes con obesidad mórbida.

OBJECTIVES: To compare the clinical effect of mivacurium in morbidly obese and normal-weight patients. PATIENTS AND METHODS: Ten morbidly obese patients (body mass index >40) and 10 normal-weight patients (body mass index, 21-24) with normal plasma cholinesterase levels. Anesthesia was provided with propofol and remifentanil in continuous infusion and a mixture of oxygen and nitrous oxide. Mivacurium was administered at a dose based on the patient's weight (0.15 mg x kg(-1)). The neuromuscular block was monitored by train-of-four (TOF) acceleromyography after stimulation of the cubital nerve at the forearm. We measured the onset time (time from administration of the muscle relaxant to 95% twitch depression), duration of block (times from dosing to 5% recovery after the first twitch [T1] of a TOF stimulus and to a TOF ratio of 80%), and the recovery indices (time between 25% and 75% recovery after T1 and between recovery of TOF ratios of 25% and 80%). Groups were compared with the Student t test. RESULTS: Mean (SD) onset time was similar in the 2 groups (normal weight 2.73 [1] minutes vs morbidly obese 1.91 [0.6] minutes). Other measures of duration and recovery were also similar in the 2 groups, respectively: duration of dose-T1 5%, 12.23 (2.1) vs 11.45 (3) minutes; dose-TOF ratio 80%, 24.71 (4.6) vs 24.81 (5) minutes); recovery index T1 25%-75%, 6.45 (2) vs 5.56 (1) minutes; recovery of TOF ratio T1 25%-80%, 9 (2) vs 10.11 (2) minutes. CONCLUSION: We found no differences in the clinical effect of mivacurium between morbidly obese and normal-weight patients when doses were based on real weight.

Time course and train-of-four fade of mivacurium block during sevoflurane and intravenous anaesthesia.

BACKGROUND AND OBJECTIVE: Volatile anaesthetics inhibit nicotinic acetylcholine receptors at clinically relevant concentrations with higher affinity for the neuronal nicotinic receptor. The inhibitory effects of propofol on nicotinic receptors have only been documented at supraclinical concentrations. The aim of this study was to determine recovery properties and train-of-four (TOF) fade of mivacurium during sevoflurane and propofol anaesthesia, in order to examine any differences both in the enhancement of the neuromuscular block (postjunctional effects) and in TOF fade (prejunctional effects). METHODS: Twenty ASA I-II adult patients were randomly allocated to maintenance of anaesthesia with sevoflurane (end-tidal concentration 2%) or propofol. Neuromuscular block was assessed by acceleromyography and a single dose of mivacurium (0.15 mg kg(-1)) was administered (in the sevoflurane group after 30 min of exposure to sevoflurane). We measured time for recovery of the first twitch of the TOF (T1) from 25-75%, time from 25% recovery of T1 to achieving a TOF ratio (TOFR) of 0.8, TOFR at 50%, 75% and 90% recovery of T1, and height of T1 at TOFR of 0.7 and 0.9. Data were tested using t-test for independent samples. RESULTS: Recovery times (mean (95% confidence interval, CI)) of mivacurium in the sevoflurane group (T1 25-75%, 11.3 (8.1-14.5) min; T1 25%-TOFR0.8, 19.1 (15.7-22.5) min) were significantly longer (P < 0.05) than in the propofol group (T1 25-75%, 6.5 (5.2-7.7) min; T1 25%-TOFR0.8, 11.3 (7.8-10.3) min). No differences were found in the relations between TOFR and T1 or vice versa, between the groups. CONCLUSIONS: Recovery times after a single dose of mivacurium were prolonged by sevoflurane compared with propofol but no differences in TOF fade were observed between the two anaesthetics.

[Effect of sevoflurane on the neuromuscular blockade produced by continuous mivacurium infusion ]. / Efecto de sevoflurano sobre el bloqueo neuromuscular de mivacurio en infusión continua.

OBJECTIVE: To evaluate the effect of sevoflurane on a neuromuscular block from mivacurium in continuous infusion. PATIENTS AND METHODS: Fourteen ASA I-II patients receiving general anesthesia for orthopedic procedures on the knee. The neuromuscular block was monitored by acceleromyography in the adductor pollicis muscle after stimulation of the cubital nerve. Anaesthesia was induced with propofol and remifentanil. After orotracheal intubation, mivacurium was given in continuous infusion adjusted to obtain a stable submaximal block defined as a variation in the block of 3% more or less for 10 minutes (first response on a train of four [T1] between 40% and 60% of the calibrated value). Values for T1, the T4/T1 ratio (TR) and temperature over the thenar eminence were recorded at 3 moments: control moment (infusion of mivacurium and sevoflurane at an expired fraction of 1.5% for 30 minutes) and post-sevoflurane moment (perfusion of mivacurium and sevoflurane at an expired fraction of 0% for 15 minutes). Statistical analysis was by analysis of variance and post-hoc contrast (Tukey). RESULTS: Results are expressed as means with standard error between parentheses. We found that values at T1(%) and TR(%) were significantly lower at the sevoflurane moments (T1 = 43.11 [1]; TR = 25.68 [1]) and the post-sevoflurane moment (T1 = 36.29 [2]; TR = 25.06 [2]) than at the control moment (T1 = 53.18 [1]; TR = 38.93 [1]) (P < .05). T1 was significantly lower at the post-sevoflurane moment than at the sevoflurane moment (P < .05) but TR did not differ significantly. CONCLUSION: Sevoflurane causes a significant increase in the neuromuscular block maintained by mivacurium in continuous infusion and the increase lasts at least 15 minutes after the halogenated agent is cleared from blood.

[Unsuspected prolonged activated partial thromboplastin time in emergency surgery. Diagnostic and therapeutic guide]. / Tiempo de tromboplastina parcial activado prolongado no sospechado en cirugía de urgencia. Orientación diagnóstica y terapéutica.

Systematic complementary testing for asymptomatic patients before surgery yields an unexpectedly high percentage of anomalous results. Such results rarely affect perioperative management of the patient but may lead to unnecessary delays, which are potentially of great importance in emergency surgery. A 55-year-old woman with a clinical diagnosis of acute appendicitis was seen to have a prolonged activated partial thromboplastin time (APTT) of 1.94 before surgery. The patient's history did not suggest a coagulation disorder was likely, and when mixing normal and problem plasma failed to correct the APTT, we suspected an unspecified circulating anticoagulant was present. Surgery was delayed no further and no measures were taken. No excessive bleeding occurred during surgery or postoperative recovery. The main possible diagnoses for a women with unforeseen prolonged APTT are the presence of an unspecified circulating anticoagulant, factor XI or factor XII deficiency, or factor VIII deficiency associated with von Willebrand disease. Focusing on detecting a coagulation disorder while taking a patient's history and performing a simple laboratory test (mixing normal and problem plasma) can be useful for orienting management in emergency surgery.