Sarcopenic Obesity: An Appraisal of the Current Status of Knowledge and Management in Elderly People.

Today's increased life expectancy highlights both age-related changes in body composition and a higher prevalence of obesity. Sarcopenic obesity (SO) is assuming a prominent role in cardio-metabolic risk because of the double metabolic burden derived from low muscle mass (sarcopenia) and excess adiposity (obesity). This review evaluates the related studies that have been published over the past 10 years in order to give an updated overview of this new syndrome. There is no consensus on the definition of SO due to the wide heterogeneity of diagnostic criteria and choice of body composition components needed to assess this phenotype. There is a growing body of evidence that the ethio-pathogenesis of SO is complex and multi-factorial, as the consequences are a combination of the outcomes of both sarcopenia and obesity, where the effects are maximised. In order to manage SO, it is important to make lifestyle changes that incorporate weight loss, physical exercise and protein supplementation.

Effect of positive end-expiratory pressure on pulmonary shunt and dynamic compliance during abdominal surgery.

BACKGROUND: General anaesthesia decreases pulmonary compliance and increases pulmonary shunt due to the development of atelectasis. The presence of capnoperitoneum during laparoscopic surgery may further decrease functional residual capacity, promoting an increased amount of atelectasis compared with laparotomy. The aim of this study was to evaluate the effects of different levels of positive end-expiratory pressure (PEEP) in both types of surgery and to investigate whether higher levels of PEEP should be used during laparoscopic surgery. METHODS: This prospective observational study included 52 patients undergoing either laparotomy or laparoscopic surgery. Three levels of PEEP were applied in random order: (1) zero (ZEEP), (2) 5 cmH2O and (3) 10 cmH2O. Pulmonary shunt and ventilation/perfusion mismatch were assessed by the automatic lung parameter estimator system. RESULTS: Pulmonary shunt was similar in both groups. However, in laparotomy, a PEEP of 5 cmH2O significantly decreased shunt when compared with ZEEP (12 vs 6%; P=0.001), with additional PEEP having no further effect. In laparoscopic surgery, a significant reduction in shunt (13 vs 6%; P=0.001) was obtained only at a PEEP of 10 cmH2O. Although laparoscopic surgery was associated with a lower pulmonary compliance, increasing levels of PEEP were able to ameliorate it in both groups. CONCLUSION: Both surgeries have similar negative effects on pulmonary shunt, while the presence of capnoperitoneum reduced only the pulmonary compliance. It appears that a more aggressive PEEP level is required to reduce shunt and to maximize compliance in case of laparoscopic surgery.

A methodological approach for determination of maximal inspiratory pressure in patients undergoing invasive mechanical ventilation.

BACKGROUND: Maximal inspiratory pressure (MIP) can help to evaluate inspiratory muscle strength. However its determination in ventilated patients is cumbersome and needs special equipment. We hypothesized that MIP could be obtained by using the expiratory hold knob of the ventilator. The aim of this study was to verify whether: 1) the end expiratory occlusion technique can be used for MIP determination; and 2) if this technique provides different results compared to those obtained by the traditional method of MIP calculation. METHODS: We studied 23 consecutive patients undergoing mechanical ventilation for acute respiratory failure. The MIP was determined by two different methods, both based on occluding the airway for 20 seconds. This occlusion was obtained either by pressing the expiratory hold knob of the ventilator; or by detaching the patient from the ventilator circuit and using a noiseless pneumatic shutter placed on the inspiratory line of a two-way valve that allows expiration but prevents inspiration. RESULTS: The average values of MIP obtained by using either the hold knob of the ventilator or the noiseless pneumatic shutter were -46±14 cmH2O and -56±13 cmH2O, respectively. The linear regression analysis showed a significant correlation between MIPVent and MIPOcc (r2=0.95), although the Bland- Altman analysis revealed that they are not clinically comparable. CONCLUSION: MIP can be easily determined at the bedside by pressing the expiratory hold knob of ventilator. However, MIPVent and MIPOcc are different in terms of absolute value probably because they were determined at diverse lung volume.

Mitochondrial alterations, oxidative stress and neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial disorder characterized by the progressive deterioration of neuronal networks. The primary cause and sequence of its progression are only partially understood but abnormalities in folding and accumulation of insoluble proteins such as beta-amyloid and Tau-protein are both associated with the pathogenesis of AD. Mitochondria play a crucial role in cell survival and death, and changes in mitochondrial structure and/or function are related to many human diseases. Increasing evidence suggests that compromised mitochondrial function contributes to the aging process and thus may increase the risk of AD. Dysfunctional mitochondria contribute to reactive oxygen species which can lead to extensive macromolecule oxidative damage and the progression of amyloid pathology. Oxidative stress and amyloid toxicity leave neurons chemically vulnerable. The mitochondrial toxicity induced by beta-amyloid is still not clear but may include numerous mechanisms, such as the increased permeability of mitochondrial membranes, the disruption of calcium homeostasis, the alteration of oxidative phosphorylation with a consequent overproduction of reactive oxygen species. Other mechanisms have been associated with the pathophysiology of AD. Inflammatory changes are observed in AD brain overall, particularly at the amyloid deposits, which are rich in activated microglia. Once stimulated, the microglia release a wide variety of pro-inflammatory mediators including cytokines, complement components and free radicals, all of which potentially contribute to further neuronal dysfunction and eventually death. Clinically, novel approaches to visualize early neuroinflammation in the human brain are needed to improve the monitoring and control of therapeutic strategies that target inflammatory and other pathological mechanisms. Similarly, there is growing interest in developing agents that modulate mitochondrial function.

Effects of esomeprazole on glutathione levels and mitochondrial oxidative phosphorylation in the gastric mucosa of rats treated with indomethacin.

Proton pump inhibitors exert their preventive and healing effects on gastropathy induced by nonsteroidal anti-inflammatory drug (NSAIDs) by a dual action: the antisecretory and the antioxidant effect. The latter was investigated by using esomeprazole against indomethacin-induced gastric mucosa lesions in rats and assessed by a histomorphometric analysis. Treatment by intragastric gavage were 1% methocel as vehicle; esomeprazole 10, 30, or 60 micromol/kg; indomethacin 100 micromol/kg; and esomeprazole 10, 30, or 60 micromol/kg plus indomethacin 100 micromol/kg. The evaluation of glutathione (GSH) levels and respiratory chain complex activities [nicotinamide adenine dinucleotide, reduced (NADH)-ubiquinone oxidoreductase, succinate dehydrogenase, cytochrome C reductase, cytochrome oxidase] was performed in the isolated gastric mucosa. Esomeprazole (10-60 micromol/kg) dose dependently reversed, up to complete recovery, the inhibitory effect of indomethacin on GSH levels (approximately 60% inhibition) and mitochondrial enzyme activities (inhibition ranging from 60% to 75%). Indomethacin-induced mucosal injuries were reduced by esomeprazole. Thus, in addition to inhibiting acid secretion, the gastroprotective effect of esomeprazole can be ascribed to a reduction in gastric oxidative injury.

Energy expenditure and nutritional adequacy of rehabilitation paraplegics with asymptomatic bacteriuria and pressure sores.

OBJECTIVE: To measure resting energy expenditure (REE) in a group of people with postacute paraplegia, quantify the impact of asymptomatic bacteriuria and pressure sore(s) on patients' metabolic rate, and estimate the adequacy of patients' nutritional intakes to preserve patients' protein levels. MATERIAL AND METHODS: Ten males with post-acute paraplegia aged 42.1+/-18.7 years. We evaluated: height, body mass index (BMI), resting energy expenditure (REE), total daily calorie requirement (E), 24-h urine creatinine excretion (Cru), creatinine index (CI), and nitrogen balance (NB). RESULTS: Subjects with paraplegia showed high erythrocyte sedimentation rates. As a group, they had normal resting calorie consumption when REE was normalized for unit of urine creatinine (REE/Cru), it was higher in patients than in controls. Six of the 10 patients had a low calorie intake: of these only three had a negative nitrogen balance. CONCLUSION: In conclusion, the resting energy expenditure of the subjects with significant bacteriuria and pressure sore(s) of 23.7 kcal/kg/day suggests that a large portion of patients may have an inadequate calorie protein intake to preserve their nutritional status. The clinical significance of this study is that 28.5 kcal/kg/day may be the lower calorie threshold to meet the metabolic demands of people with apyretic paraplegia with bacteriuria and pressure sore(s).

Responsiveness to intravenous administration of salbutamol in chronic obstructive pulmonary disease patients with acute respiratory failure.

OBJECTIVE: In chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure (ARF), bronchodilating agents administered by inhalation have, in general, little effect on dynamic hyperinflation and concurrent static intrinsic positive end-expiratory pressure (PEEPi,st). Since in COPD the severely obstructed segments of the lung may not be reached by inhaled medication, we reasoned that drug efficiency may be enhanced by intravenous administration of the agent. DESIGN: Physiological study. SETTING: Two four-bed surgical-medical ICUs of a university hospital. PATIENTS: Fourteen COPD patients were studied within 36 h from the onset of ARF. MEASUREMENTS AND RESULTS: Static compliance (Cst,rs), minimal (Rmin,rs) and additional (DeltaRrs) resistance of the respiratory system, and PEEPi,st were measured before and after intravenous administration of salbutamol. All patients had limitation of air flow before and after salbutamol administration. On average, after salbutamol there was a small, though significant, decrease in Rmin,rs (-9%), DeltaRrs (-12%) and PEEPi,st (-8%). CONCLUSION: The changes in resistance and PEEPi,st after intravenous administration of salbutamol were too small to be of clinical significance.

Predictors of weaning outcome in chronic obstructive pulmonary disease patients.

Several threshold values for predicting weaning outcome from mechanical ventilation have been proposed. These values, however, have been obtained in nonhomogeneous patient populations. The aim of the present study was to determine the threshold values in chronic obstructive pulmonary disease (COPD) patients and compare them to those reported for nonhomogeneous patient populations. The initial weaning trial included 81 COPD patients. Fifty-three of them underwent a successful weaning trial, whereas 28 failed it. The latter were enrolled into the present investigation, and were restudied during a subsequent successful trial. The weaning indices used were those reported in the literature. The threshold values obtained were within 10% of those reported for a nonhomogeneous patients population only for tidal volume and effective compliance. The classification error was <20% for maximal inspiratory pressure (MIP), occluded inspiratory pressure swing (deltaPI)/MIP, rapid and shallow breathing (respiratory frequency/tidal volume), and compliance, rate, oxygenation, pressure index (CROP), whereas the area under the receiver operating characteristic curves was >0.9 only for deltaPI/MIP and CROP. In conclusion, the threshold values obtained in chronic obstructive pulmonary disease patients who failed the first weaning attempt differed from those previously reported. Although a gold standard weaning index is not available for chronic obstructive pulmonary disease patients, the occluded inspiratory pressure swing/ maximal inspiratory pressure and compliance, rate, oxygenation, pressure index may be candidates for such a role.

Presumptive delayed gas embolism after laparoscopic cholecystectomy.

A 50-year-old woman, with a history of arterial hypertension treated with beta-blocker and Ca-antagonist, presented cardiac arrest 6 hours after elective laparoscopic cholecystectomy. During surgical intervention, arterial hypotension without any respiratory change was observed. Dyspnea, asthenia and anxiety were the clinical signs appearing approximately 2 hours before cardiac arrest. After resuscitation, myocardial infarction, dissecting thoracic aortic aneurysm and major pulmonary thromboembolism were excluded. The signs of increased resistance to the right ventricular outflow and the relevant alteration of coagulation tests, lasting only a few hours, suggested venous gas embolism. Subsequently, the patient presented a cortical blindness, persisting at hospital discharge. The anesthetists should be aware about the complication that we observed after laparoscopic surgery. The least sign of cardiorespiratory instability appearing in the postoperative period must be taken into account and signal the need for increased monitoring.

The effects of aging on enzyme activities and metabolite concentrations in skeletal muscle from sedentary male and female subjects.

Aging affects the metabolic capacity of skeletal muscle, in particular the glycolytic and respiratory capacities. The purpose of this study was to quantify biochemical alterations due to aging in muscular metabolic capacity in human skeletal muscles in sedentary subjects. The activities of various marker enzymes and metabolites related to glycolysis, Krebs' cycle and the electron transfer chain and high energy phosphate compounds were measured in muscle biopsies from the rectus abdominis, vastus lateralis, and gluteus maximus muscles of 76 sedentary subjects (32 males and 44 females) between 15 and 91 yr. No significant differences between males and females were found, but changes related to age were: a decrease in hexokinase and lactate dehydrogenase activities in the rectus abdominis; a decrease in citrate synthase activity and citrate in the vastus lateralis; an increase in pyruvate kinase activity and a decrease in ATP and creatine phosphate concentrations in the gluteus maximus. These data suggest that distinct muscles may respond differently to aging regardless of sex in sedentary subjects.

Respiratory mechanics during and after anaesthesia for major vascular surgery.

To evaluate the effects of major vascular surgery on respiratory mechanics, 11 patients undergoing general anaesthesia for abdominal aortic surgery were studied. Before aortic cross-clamping, chest wall elastance and resistance both increased (by 126% and 58%, respectively) when surgical retractors were placed. After aortic cross-clamping, lung elastance increased by 29%, accompanied by a decrease in cardiac index (22%) and an increase in pulmonary (17%) and systemic (15%) vascular resistance. After aortic unclamping, lung elastance decreased, although it remained higher than baseline values (by 12%). All cardiovascular variables returned to the values obtained before aortic cross-clamping.

Multicenter trial comparing tramadol and morphine for pain after abdominal surgery.

Seventy patients (40 male, 30 female), mean (SD) age 60.8 +/- 13.7 years were treated with parenteral morphine (10 mg/1 ml ampul) or tramadol (100 mg/2 ml ampul) to verify their analgesic effects in pain following abdominal surgery. The multicenter trial followed an open, controlled experimental design between patients, randomized within the centers. The drugs were given by intramuscular injection, as requested by patients, starting in the postoperative period when pain was more than 70 mm, assessed on a visual analog scale. Patients were allowed up to six ampuls of tramadol or morphine in the 24-h trial but in the first 4 h, if they asked for supplementary analgesic, only diclofenac (75 mg in a 3-ml ampul) was allowed. Both test drugs gave rapid and constant pain relief. After the first dose, pain intensity was reduced 36.2% with tramadol, and 51% with morphine; the pain-free interval was similar for both treatments. The quality of sleep and the number of hours of sleep the night after surgery were similar for both groups. Tramadol was tolerated better, giving rise to no untoward reactions; with morphine there was one case of mild respiratory depression. In abdominal surgery, therefore, tramadol given by intramuscular injection has postoperative analgesic activity similar to morphine, but is better tolerated.

Plasma dopamine concentration and effects of low dopamine doses on urinary output after major vascular surgery.

To evaluate plasma dopamine concentration and the effects of low doses infusion on urinary output after abdominal vascular surgery in patients with renal function impairment we performed a prospective clinical study. Twenty hemodynamically stable patients (mean age 66.6 years), with serum creatinine concentration < 2 mg %, who undergoing general anesthesia for major vascular surgery participated. A low dose of dopamine (3 micrograms/kg/min) was administrated to patients with postoperative protracted urinary output < 0.5 ml/kg/hr for at least eight hours. Plasmatic determinations were taken at T0 (no dopamine administration), when urinary output began to increase, or if not, after two hours (T1), at eight (T2), and 24 (T3) hours after the beginning of infusion. After 24 hours the dopamine infusion was stopped and the patient's plasmatic level was measured four hours later (T4). Dopamine plasma concentrations were measured using high-performance liquid chromatography. Plasma dopamine concentration increased in all patients and reached a steady state at T2 (T2 = 76.41 +/- 16.84 ng/ml). Dopamine induced a concentration-dependent increase in urinary output (T0 = 0.45 +/- 0.14; T1 = 1.49 +/- 1.11; T2 = 2.34 +/- 1.44; T3 = 1.57 +/- 0.57; T4 = 0.85 +/- 0.7 ml/kg/hr). Three patients did not have an enhanced urinary output after dopamine infusion; they did have a prolonged clamping time and operation time (162 +/- 24 and 570 +/ 30 min, respectively). We conclude that low dose dopamine induces a dose-dependent increase of urinary output. This phenomenon also has been found in patients when their plasma concentration had not yet reached the steady-state. Lack of responsiveness to dopamine suggests a renal function impairment probably due to the prolonged aortic clamping time.

[Memory for postoperative pain six months after discharge from the hospital]. / Il ricordo del dolore postoperatorio a sei mesi dalla dimissione dall'ospedale.

OBJECTIVE: To investigate memory for postoperative pain in Intensive Care Unit (ICU) admitted patients after hospital discharge. DESIGN: Prospective study by direct interviews. METHODS: Six months after hospital discharge, we interviewed adult, postoperative, co-operative patients consecutively admitted to ICU for more than 24 hrs, resident near the hospital, who gave informed consent. We investigated intensity of postoperative pain and recollections of critical care reported by patients. The following data were collected from medical records: type and duration of surgical intervention, type of anaesthesia and fentanyl dose, severity of illness at ICU admission, ICU and hospital (after ICU) length of stay and postoperative administration of morphine. RESULTS: Of 130 patients interviewed, 82 (63%) reported no pain, 27 (21%) low and 21 (16%) more than low pain. Among these 3 groups of patients, there was no statistically significant difference in all the variables collected from medical records. Patients who remembered more than low pain recorded emotional distress more frequently (p < 0.001) and physical discomfort less frequently (p < 0.01) than patients whose pain was absent or low. CONCLUSIONS: Most patients report that postoperative pain, during their ICU stay, was absent or low. Emotional distress seems to be related to memory for postoperative pain.

[Respiratory circuits and infections of the airway]. / Circuiti dei respiratori e infezioni delle vie aeree.

OBJECTIVE: To study the effects of ventilator circuit changes on the rate of airway infections and to investigate the relationship between the microorganisms responsible for circuit colonization and those responsible for infection. DESIGN: Prospective study, carried out in two different periods, of one year duration each. SETTING: General Intensive Care Units (ICUs) in a University Hospital. PATIENTS: Seventy-eight patients, requiring mechanical ventilation (VAM) for more than 5 days, were enrolled. They were divided into two groups: in the first (group I, n. 36, 1st period) the ventilator circuit was changed every 5 days; in the second (group II, n. 42, 2nd period) every 10 days. INTERVENTION: Ventilator circuit change every 5 or 10 days. Daily culvert and filling of cascade humidifiers with sterile irrigation water. Daily replacement of mount catheter. MEASUREMENTS: Qualitative cultures of tracheobronchial aspirate and of fluid from the humidifying cascades and the expiratory tubing traps. RESULTS: The two groups were similar. Pneumonia and tracheobronchitis were found in the 25% and 11% of patients of group I and in 26% and 12% of those of group II respectively. The VAM duration was 26.5 +/- 15 days in patients who developed airway infection, and 12.9 +/- 11.6 days (p < 0.001) in patients who did not. The Gram+ organisms were predominant. An identical microorganism was found both in the tracheo-bronchial aspirate and in the circuit in 44 of 78 (56%) patients; no difference was found between infected (16 of 29) and non infected (28 of 49) patients. CONCLUSIONS: Changing the ventilator circuit every 10 days rather than every 5 days, does not increase the incidence of airway infections and result in considerable savings in the expenses of tubing and personnel time. The infection or colonization rates due to the same microorganisms are quite low and it seems not useful to make routine cultures of fluid from humidifying cascades and the expiratory tubing traps in order to characterize in time the microorganism that could be responsible of airway infections.

Photoinduction of micronuclei by 4,4',6-trimethylangelicin and 8-methoxypsoralen in different experimental models.

The frequencies of micronuclei induced by treatment with 4,4',6-trimethylangelicin (TMA) and 8-methoxypsoralen (8-MOP) have been compared in the following experimental models: (1) peripheral normochromatic erythrocytes (NCE) during 10 days after single p.o. administration of TMA or 8-MOP in male and female mice; (2) peripheral NCE during photocarcinogenesis by TMA or 8-MOP topically administered to female mice; (3) primary cultures of human skin fibroblasts treated with TMA or 8-MOP. The frequency of micronuclei in peripheral NCE of mice (both sexes) was significantly enhanced after p.o. administration of TMA or 8-MOP. This latter was more active than TMA in inducing chromosomal damage. No increased frequencies of micronuclei in peripheral NCE were detected in mice subjected to TMA or 8-MOP photocarcinogenic treatment, even when malignancies developed. In human fibroblast cultures, at equimolar concentrations, the induction of lethal effects by TMA in the presence of 365-nm radiation was higher than that exerted by 8-MOP. At equal survival, however, TMA showed practically the same activity as 8-MOP in the induction of micronuclei. Our findings provide evidence of genotoxicity by TMA administered p.o. without irradiation and give further information about photogenotoxicity of these substances.

Carotenoids reduce the chromosomal damage induced by bleomycin in human cultured lymphocytes.

The supplementation with beta-carotene and canthaxanthin, two carotenoids with and without pro-vitamin A activity, reduced in vitro the number of micronuclei induced in human cultured lymphocytes by the chemotherapeutic radiomimetic drug bleomycin. The genotoxic activity of this substance is supposed to be mediated by a free radical mechanism. The reduction of micronucleated cells was in correlation with donors' carotenoid blood levels. It has been observed that 20 weeks are needed, following the end of carotenoid supplementation, in order to return to the high levels of micronuclei induced by bleomycin. It is suggested that this protective effect is due to the antioxidant properties of carotenoids acting against free radical-mediated genotoxic damage.

[Low T3 syndrome (3,3',5-triiodothyronine) in relation to the extent of surgical trauma]. / La sindrome da basso T3 (3,3', 5-triiodotironina) in relazione all'entità del trauma chirurgico.

Thirty patients undergoing extra-thyroid surgery were divided into two groups (A and B) according to the extent of surgical stress (Group A: major surgery; Group B; minor surgery). Thyroid hormone levels were measured before the operation and up to the 3rd postoperative day in Group B and up to the 7th postoperative day in Group A. A low T3 syndrome was observed in all 30 patients examined of the first postoperative day (reduction of T3 and increase in rT3 without alterations of total thyroxin or signs of hypothyroidism) with normalisation of thyroid values by 3rd postoperative in Group B and later in Group A. The persistence of the syndrome in the latter group was due to the extent of surgical stress, the duration of anesthesia, the presence of stress factors such as staying in intensive therapy, painful symptoms and a negative energy balance during the first days following operation. This syndrome is indicative of a physiological adaptation process to reduce O2 consumption, basal metabolism and in particular protein catabolism.