Chemotherapy-Associated Liver Injuries: Unmet Needs and New Insights for Surgical Oncologists

Annals of Surgical Oncology -     

Plasma troponins as markers of myocardial damage during cardiac surgery with extracorporeal circulation

All types of cardiac surgery involve considerable injury to the myocardium. However, it is difficult to differentiate, in the immediate post-operative state, between ischemic alterations associated with the cardiac surgery itself and the pathological alterations of a peri-operative myocardial infarction. The diagnosis of damaged myocardium, classically performed with the enzymatic markers creatine kinase (CK) and its muscle fraction (CK-MB), has become more precise with the option of measuring cardiac troponins T and I. We measured these markers in 58 patients undergoing elective cardiac surgery with extra-corporeal circulation (ECC). The patients included 37 cases undergoing valve surgery, 14 for coronary revascularization, 6 for mixed procedures, and 1 for closure of an inter-atrial communication. The markers were measured in plasma at baseline (at anesthesia initiation), 5 min post-ECC commencement, following aorta de-clamping, during the surgical closure, and 6, 18 and 42 hrs after surgery. All the markers were increased significantly relative to the baseline values. Troponin I, CK and CK-MB values peaked between 6 and 18 hrs after surgery, troponin T between 18 and 42 hrs, and myoglobin at the surgical closure. The values of all markers were higher in patients undergoing coronary surgery compared to those in patients undergoing valve surgery. In the evaluation of myocardial damage after surgery, the measurement of classical markers such as CK and myoglobin remain valid, but other markers such as troponins provide significant additional diagnostic benefit and, thus, need to be included in the routine biochemical measurements for monitoring myocardial damage associated with the surgical procedure.     

Detection of wheezing during maximal forced exhalation in patients with obstructed airways

STUDY OBJECTIVES: Wheezing is a common clinical finding in patients with asthma and COPD during episodes of severe airway obstruction, and can also be heard in normal subjects during forced expiratory maneuvers; however, the properties of wheezing are difficult to perceive and quantify during auscultation. We therefore developed and evaluated a new technique for recording and analyzing wheezing during forced expiratory maneuvers in a group of patients with obstructed airways (asthma, COPD) and a control group of healthy subjects. MATERIAL AND METHODS: Sixteen patients with asthma (9 men and 7 women), 6 patients with COPD (6 men), and 15 healthy subjects (7 men and 8 women) were enrolled. The patients had moderate-to-severe obstruction (FEV(1) of 40 to 53% predicted). A contact sensor on the trachea was used to record sound during forced expiratory maneuvers. Wheeze detection was carried out by a modified algorithm in a frequency-time space after applying the fast Fourier transform. RESULTS: More wheezes were recorded in patients with obstructed airways than in control subjects: asthma patients, 8.4 +/- 6.4 wheezes; COPD patients, 10.4 +/- 6.1 wheezes; and control subjects, 2.9 +/- 2.0 wheezes (mean +/- SD). The mean frequency of all detected wheezes was higher in control subjects than in patients with obstructed airways (asthma patients, 560.9 +/- 140.8 Hz; COPD patients, 669.4 +/- 250.1 Hz; and control subjects, 750.7 +/- 175.7 Hz). The total number of wheezes after terbutaline inhalation changed more in patients with obstructed airways than in control subjects. CONCLUSIONS: The new method that we describe for studying airway behavior during forced expiratory maneuvers is able to identify and analyze wheeze segments generated in patients with obstructed airways, as evidenced by the greater number of wheezes detected in the patient group, the main finding of this study. This method clearly and objectively identifies the presence of obstructive disease.     

Functional Consequences of Eccentric Contractions of the Diaphragm

Introduction and ObjectivesEccentric contractions are those that occur after a muscle has been stretched, and they can predispose the muscle to damage. Most previous studies have been performed on limb muscles, and the potential consequences of eccentric contractions on the respiratory muscles are therefore unknown. The aim of this study was to evaluate the effects of repeated eccentric contractions on diaphragmatic function.MethodsIn 6 dogs, the diaphragm was stretched by applying pressure on the abdominal wall, and consecutive series of eccentric contractions were induced by bilateral supramaximal stimulation. The effect of these contractions on the diaphragm was then evaluated by applying bilateral twitch and tetanic stimulation of the phrenic nerves and measuring the changes in abdominal pressure and the shortening of the right and left hemidiaphragms (by sonomicrometry). Structural study of the muscle was also performed in 4 animals.ResultsEccentric contractions were successfully achieved in all cases. Stimulation-induced diaphragmatic pressures became lower immediately after these contractions: twitch pressure fell by 53% and tetanic pressure by 67% after the first 10 eccentric contractions (P<.001 in both cases). Tetanic stimulation also demonstrated an early deterioration in contractility, which fell by 29% in the right hemidiaphragm (P<.05) and by 14% in the left hemidiaphragm (P<.001). Functional impairment was persistent, lasting at least 12 hours, and was associated with sarcomeric and sarcolemmal damage.ConclusionsThis experimental model, which enabled the effects of eccentric contractions to be studied in the diaphragm, revealed a deterioration of muscle function that persisted for hours and that appeared to be partly due to structural damage. In the clinical setting, physiologic or therapeutic maneuvers that increase the resting length of the diaphragm should be used with caution.     

Modifications of Diaphragmatic Activity Induced by Midline Laparotomy and Changes in Abdominal Wall Compliance

Introduction and ObjectiveDiaphragmatic activity varies with the initial length of the muscle. Our objective was to evaluate the influence of surgery and changes in abdominal wall compliance on diaphragmatic activity.MethodsBoth phrenic nerves in 7 mongrel dogs were stimulated electrically with single supramaximal pulses (twitch). The gastric (Pga) and transdiaphragmatic (Pdi) pressures generated and muscle shortening (sonomicrometry) were used to evaluate diaphragmatic activity, which was determined at baseline, after midline laparotomy, with an elastic abdominal bandage, and with a rigid circular cast. Abdominal pressure was then gradually increased in order to induce progressive lengthening of the diaphragm.ResultsAfter laparotomy, the pressures were somewhat lower (by 12%) than at baseline. The elastic bandage produced a slight increase in the pressure generated by the diaphragm (mean [SE] values: Pga, from 4.2 [0.3] cm H₂O to 6.3 [0.9] cm H₂O, P<.01; Pdi, from 12.1 [2.0] cm H₂O to 15.4 [1.8] cm H₂O, P<.05]), and these values increased even further with the rigid cast (Pga, to 12.6 [1.5] cm H₂O; Pdi, to 20.2 [2.3] cm H₂O; P<.01 for both comparisons); this occurred despite smaller degrees of muscle shortening: by 57% [5%] of the initial length at functional residual capacity at baseline, by 49% [5%] with the bandage (P<.05), and by 39% [6%] with the cast (P<.01). With progressive lengthening of the muscle, its contractile efficacy increased up to a certain point (105% of the length at functional residual capacity), after which it began to decline.ConclusionsAbdominal wall compliance plays an important role in the diaphragmatic response to stimulation. This appears to be due mainly to changes in its length at rest.     

Effects of inhaled platelet activating factor on bronchial responsiveness in patients with symptomatic and asymptomatic pulmonary embolism.

To determine the possible role of platelet-activating factor (PAF) in pulmonary embolism (PE), the reactivity of the airways to inhaled PAF, using doses ranging from 6.25 to 400 micrograms, was examined in 24 patients with a past episode of PE. Twelve of these patients had experienced acute respiratory insufficiency during the episode (with or without additional symptoms). None of the remaining 12 patients had experienced any respiratory symptoms during the PE episode. Diagnosis was established by means of a ventilation-perfusion lung scan performed when admitted to the hospital because of deep venous thrombosis (DVT) in the lower limbs. Nonspecific bronchial reactivity as measured by the response to bronchoprovocation testing with methacholine showed no significant differences between both groups. PAF caused a dose-dependent bronchoconstriction defined by at least a 35 percent decrease in specific airway conductance (SGaw) in all patients. The average dose of PAF needed to decrease SGaw 35 percent was significantly lower in patients who had had a symptomatic PE than in those with asymptomatic PE (p = 0.011). This finding suggests that patients who suffered from symptomatic PE may present a greater airway reactivity to inhaled PAF. This different behavior might explain the existence of some of the respiratory symptoms of PE, which could be attributed to PAF-related effects. However, additional studies are needed to evaluate the role of PAF in PE.     

How many manoeuvres should be done to measure maximal inspiratory mouth pressure in patients with chronic airflow obstruction?

To determine the number of maximal mouth pressure manoeuvres needed to obtain a reproducible value of maximal inspiratory mouth pressure (MIP), we studied 44 patients with chronic airflow obstruction, with a mean (SD) % predicted FEV1 value of 53.9 (25), who were clinically stable. Maximal inspiratory mouth pressure was determined with an anaeroid manometer during maximal inspiratory efforts in a quasi static condition at residual volume. All patients performed 20 consecutive maximal inspiratory mouth manoeuvres, each one separated by 30-40 seconds. The mean (SD) values of MIP varied from 71.5 (25.5) cm H2O at the first measurement to 80.1 (27) cm H2O at the last measurement. Maximal values of MIP were usually achieved after nine determinations. It is concluded that to obtain a reproducible MIP value in patients with chronic airflow obstruction who are untrained and unexperienced in such manoeuvres a minimum of nine technically acceptable maximal mouth pressure manoeuvres should be performed.     

Multiclass classification of subjects with sleep apnoea-hypopnoea syndrome through snoring analysis

The gold standard for diagnosing sleep apnoea-hypopnoea syndrome (SAHS) is polysomnography (PSG), an expensive, labour-intensive and time-consuming procedure. Accordingly, it would be very useful to have a screening method to allow early assessment of the severity of a subject, prior to his/her referral for PSG. Several differences have been reported between simple snorers and SAHS patients in the acoustic characteristics of snoring and its variability. In this paper, snores are fully characterised in the time domain, by their sound intensity and pitch, and in the frequency domain, by their formant frequencies and several shape and energy ratio measurements. We show that accurate multiclass classification of snoring subjects, with three levels of SAHS, can be achieved on the basis of acoustic analysis of snoring alone, without any requiring information on the duration or the number of apnoeas. Several classification methods are examined. The best of the approaches assessed is a Bayes model using a kernel density estimation method, although good results can also be obtained by a suitable combination of two binary logistic regression models. Multiclass snore-based classification allows early stratification of subjects according to their severity. This could be the basis of a single channel, snore-based screening procedure for SAHS.