Candidemia in intensive care unit: a nationwide prospective observational survey (GISIA-3 study) and review of the European literature from 2000 through 2013.

BACKGROUND: Candida bloodstream infections (BSI) represent an important problem in Intensive Care Units (ICUs). The epidemiology of candidemia is changing with an increase in the proportion of Candida (C.) non-albicans. OBJECTIVES: An Italian 2-year observational survey on ICU was conducted to evaluate the species distribution and possible differences between BSI caused by C. albicans and C. non-albicans. For comparative purposes, we performed a European literature-based review to evaluate distribution and frequency of Candida spp. causing ICU candidemia, during the period 2000-2013. MATERIALS AND METHODS: This laboratory-based survey involved 15 microbiology centers (GISIA-3 study). All candidemia episodes in adult patients were considered. Data were prospectively collected from 2007 to 2008. PubMed was searched for peer-reviewed articles. RESULTS: In total, 462 candidemia episodes were collected. C. albicans accounted for 49.4% of the isolates, followed by C. parapsilosis (26.2%) and C. glabrata (10.4%). Mortality was higher in patients with C. non-albicans than C. albicans (47.3% vs. 32.4 %, p > 0.05). Among risk factors, parenteral nutrition was more common (p = 0.02) in non-albicans candidemia, while surgery was more frequent (p = 0.02) in C. albicans candidemia. Twenty-four relevant articles were identified. C. albicans was the predominant species in almost all studies (range 37.9% -76.3%). C. glabrata was commonly isolated in the German-speaking countries, France, UK and North Europe; C. parapsilosis in Turkey, Greece and Spain. CONCLUSIONS: Although C. non-albicans BSI is increasing, our study shows that C. albicans is still the predominant species in ICU candidemia. There are differences in the epidemiology of Candida BSI among European countries, with a prevalence of C. glabrata and C. parapsilosis in Northern and Southern countries, respectively.

Routine use of a protease zymogen-based colorimetric assay for the detection of Beta-glucan and its role in clinical practice.

The detection of Aspergillus antigen (galactomannan) is considered a reliable marker for the diagnosis of invasive aspergillosis (IA), yet the sensibility and specificity of the assays commonly employed in routine are not optimal. The aim of the present study was to investigate whether the detection of another panfungal antigen, the (1,3)-b-D-glucan could have an auxiliary role in the identification of patients with IA. The study was carried out on 63 sera belonging to patients who had been screened for galactomannan, according to the clinical suspect of IA. Our data show that the positive galactomannan results were not confirmed by positive (1,3)-b-D-glucan results in patients receiving therapy with beta-lactam antibiotics associated with tazobactam, whereas in all the other cases, with the exception of four, the results of the (1,3)-b-D-glucan test were confirmatory of the galactomannan results.

Effect of an injectable cabergoline formulation on serum prolactin (PRL) and milk secretion in early postpartum Beagle bitches.

This study was conducted in order to evaluate effects on prolactin (PRL) concentration and mammary milk secretion of an injectable cabergoline formulation administered to five lactating Beagle bitches during early postpartum (PP). Bitches were bled twice daily (from PP day 3 to PP day 12) and then daily (from PP day 13 to PP day 16) to assay serum PRL. On PP day 6, a subcutaneous (SC) injection of 0.1 ml/kg of placebo was administered. On PP day 9, a SC 0.1 ml/kg dose of injectable cabergoline was administered. All bitches were checked for milk production, using a clinical scoring in order to quantify milk expression from each teat. A circadian variation of serum PRL was evident during the 6 days of pre-treatment monitoring. The day after cabergoline injection, an 80% decrease of PRL serum concentration was observed (p < 0.05). The circadian oscillatory pattern of PRL secretion disappeared after administration of cabergoline, and PRL values remained significantly lower than in the previous days for the first 60 h following treatment (p < 0.001). Milk production was drastically reduced when comparing pre-treatment to post-treatment scores (p < 0.001). A single dose of injectable cabergoline caused a significant reduction in serum PRL concentration and a significant reduction in milk flow. The injectable formulation of cabergoline appeared to be safe and well tolerated.

Vertebral hemi-resection for bone tumor with wide invasion of the vertebral canal: modified surgical method.

The authors describe a variation in the method of vertebral hemi-resection used for the treatment of neoplasms that present a wide invasion of the vertebral canal. This is followed by a review of the literature on the subject.

European Confederation of Medical Mycology (ECMM) prospective survey of candidaemia: report from one Italian region.

An ECMM epidemiological prospective survey of candidaemia was performed in one Italian region (Lombardy; population: 8 924 870) by the National Society of Medical Mycology (FIMUA) from September 1997 to December 1999. In total, 569 episodes were reported with an overall rate of 0.38/1000 admissions, 4.4/100000 patient days. Predisposing factors included presence of an intravascular catheter (89%), antibiotic treatment (88%), surgery (56%), intensive care (45%), solid tumour (28%), steroid treatment (15%), haematological malignancy (7%), HIV infection (6%), fetal immaturity (4%). Mucous membrane colonization preceded candidaemia in 83% of patients. Candida albicans was identified in 58% of cases, followed by Candida parapsilosis (15%), Candida glabrata (13%), Candida tropicalis (6%). Septic shock occurred in 95 patients. Crude mortality was 35%, the highest in C. tropicalis fungaemia (44%), the elderly (64%) and solid tumour cancer patients (43%). Intravascular catheter removal was associated with higher survival rate (71 vs. 47%). This survey underscores the importance of candidaemia in hospital settings.

Pattern of relapse in patients with osteosarcoma of the extremities treated with neoadjuvant chemotherapy.

570 patients with osteosarcoma of the extremities were treated with five different protocols of neoadjuvant chemotherapy at Rizzoli Institute between 1983 and 1995. Surgery consisted of limb salvage in 83% rotation plasty in 5% and amputation in 12%. The 5-year event-free survival (EFS) was 60% which varied according to the protocol followed, ranging from 47.6% to 66.4%. 234 patients relapsed. The pattern of relapse was analysed. The mean relapse time was 23.8 months (range: 2-96). The first site of systemic relapse was the lung in 88% (32% of these had less than three pulmonary metastases and 68% three or more), bone in 9%, lung and bone in 2% and other sites in 3%. The relapse time and the number of pulmonary metastases were strictly correlated with the efficacy of the protocol of chemotherapy used. Patients treated with the three protocols that gave a 5-year EFS of more than 60% relapsed later and had fewer pulmonary lesions than patients treated with the two protocols that gave a 5-year EFS of 47.6% and 52.5%. The rate of local recurrence was relatively low (6%). This was not correlated with the protocol or the type of surgery used: limb salvage (6.4%), rotation plasty or amputation (4.1%). However, the rate of local recurrence was very high (21.9%) in the few patients (7%) that had less than wide surgical margins. We conclude that for patients with osteosarcoma of the extremities treated with neoadjuvant chemotherapy: (a) the pattern of systemic relapse changes according to the efficacy of the protocol of chemotherapy used. This should be always considered when evaluating the preliminary results of new studies as well as in defining the time of follow-up; (b) limb salvage procedures are safe and do not jeopardise the outcome of the patient, provided that wide surgical margins are achieved.

Use of the trans-abdominal rectus abdominis flap in sacrum surgery.

The authors describe the method used to reconstruct the posterior wall of the pelvis using a flap taken from the rectus abdominis muscle after resection of the sacrum to treat neoplasm.

Vertebral tumors: differential diagnosis between primary and secondary neoplasms.

The authors discuss the criteria of differential diagnosis between primary and secondary tumors, emphasizing the role played by biopsy.

Major vertebral surgery: intra- and postoperative anaesthesia-related problems.

A personal experience concerning vertebral excision and resection in a single stage for neoplasm is discussed. The surgery requires anaesthesia of long duration, hemodynamic stability, compensation of significant blood loss, monitoring of heat loss, maintenance without injury of prolonged prone position. Experience, with 24 cases lasting an average of 14.5 hours proves that inhalation or intravenous anaesthesia with a strong analgesic component is satisfactory. Normal heat saving systems reduce intraoperative hypothermia. Transfusion is always abundant, autologous contribution is moderate. Hemodilution is well-tolerated up to Hb 7%; below this amount there may be problems of a hemodynamic and coagulative nature. The quantity and quality of filling is guided by monitoring of pre-loading pressures and availability of oxygen. There were no critical complications; all of the patients left the hospital in good condition.

[Experimental isovolemic hemodilution. Study of tissue perfusion with Hb 3% in swine]. / Emodiluizione isovolemica sperimentale. Studio sulla perfusione tessutale ad Hb 3 g% nel suino.

BACKGROUND: The aim of the study is to evaluate the limits of the compensatory mechanisms and the tissue damages caused by the low oxygen content during severe normovolemic hemodilution in pigs. METHODS: The experimental procedure was performed in 10 animals after general anaesthesia was induced and iso-hypervolemic hemodilution to Hct 10% was maintained for five hours without any intensive care. Hemodynamic, biochemical and ultrastructural parameters were detected before and at the end of hemodilution in addition to analysis of oxygen delivery/uptake and mitochondrial enzymes function. RESULTS: The collected data show: the initial good compensatory mechanism was subsequently exhausted; five animals demonstrated cardiac ischemia and low CO and two of them died before the end of the experiment; no hemodynamic and hemoxymetric data predicted the cardiac ischemia; the dilution caused alterations of some detected biochemical parameters such as hemocoagulation; no evidence of morphologic and ultrastructural tissue damage or interstitial edema; decreasing in mitochondrial enzymes activity significant only for NADH-related. CONCLUSIONS: In conclusion, it seems that, in pigs at least, the compensatory mechanisms can keep a sufficient tissue oxygen supply throughout the experimental time with the exception of cardiac muscle.

Neurologic deficit after resection of the sacrum.

The authors describe neurologic deficit (sensory, motor, and sphincteral) resulting from sacrifice of the sacral nerve roots removed during resection of the sacrum. The anatomical and functional bases of sphincteral continence and the amount of neurologic deficit are discussed based on level of sacral resection. A large review of the literature on the subject is reported and discussed. The authors emphasize how the neurophysiological bases of sphincteral continence (rectum and bladder) and of sexual ability are still not well known, and how the literature reveals disagreement on the subject. A score system is proposed to evaluate neurologic deficit. The clinical model of neurologic deficit caused by resection of the sacrum may be extended to an evaluation of post-traumatic deficit.

Pulmonary embolism associated with use of bone cement during hip arthroplasty.

Main circulatory (heart frequency, HF, intra-artery pressure, AP ECG) and respiratory (arterial oxyhemoglobin saturation SaO2, end-tidal CO2) arterial gas-analysis (HGA) parameters were recorded continually during cemented hip arthroplasty in 70 consecutive non-selected patients. The use of cement did not cause any change in the parameters obtained in 21 of the cases, reduction in arterial oxygen pressure (PaO2) ranging from 11% to 38% was observed in 44 cases, associated with simultaneous reduction in ETCO2 in 11 cases. The reduction in ETCO2 was an isolated finding in 5 of the patients. AP decreased by more than 10% in only 2 cases and there was arrhythmia in another 2 cases. These findings are strongly suggestive of pulmonary embolism encouraging the hypothesis of gas embolism previously suggested by other authors. In patients with little coronary or pulmonary reserve use of cement means an increased risk of severe hemodynamic complications.

[Evaluation of the effectiveness of NSAIDs in the prevention of postoperative pain. Comparison between pre- and postoperative administration of sodium naproxen in orthopedic surgery]. / Valutazione dell'efficacia dei FANS nella prevenzione del dolore postoperatorio. Confronto tra somministrazione pre e postoperatoria di Naprossene sodico in chirurgia ortopedica.

The aim of the study was to assess the efficacy of the preoperative sodium Naproxen administration to reduce analgesic requirements in the postoperative period. 75 patients (ASA I-II), 50 male and 25 female, aged between 25 and 70 years and weighed between 50 and 90 kg, undergoing lumbar laminectomy were subjected to the same anesthetic technique. Patients were allocated randomly to one of three groups. Group I received intravenous sodium naproxen (550 mg) immediately after induction of anesthesia. Group II received intravenous sodium Naproxen (550 mg) at the end of surgery. Group III received intravenous normal saline immediately after induction of anesthesia. Postoperative every patient was given by request intramuscular Buprenorphine (0.3 mg) for pain relief (at 6 h intervals). Buprenorphine requirements in the group I were significantly lower than in either of the other groups (p < 0.01 and p < 0.0001 respectively), while significant differences were not observed between group II and III. Moreover the 54% of patients in the group I did not require analgesic drugs in the postoperative period in opposition to the 20% of pts. in the group II and the 12% of pts. in the group III (p < 0.05 and p < 0.01 respectively). We conclude that NSAIDs when given before tissue damage may prevent nociceptor sensitisation and probably reduce hyperexcitability of the spinal cord. Preoperative administration of NSAIDs provides better protection against peripheral nerve sensitisation than postoperative administration.

Anesthesia and perioperative treatment in large resections of the pelvic girdle.

The authors examine 24 patients submitted to resection of the pelvic girdle in neoplastic pathology, illustrating the perioperative anesthesiologic procedures used. Sudden variations in blood and plasma volume and increasing hypothermia constitute the main problems. The prevention of hypothermia and continuous invasive monitoring of hemodynamic parameters and of oxygen saturation in mixed venous blood (SvO2) are of primary importance.

[Normovolemic induced hemodilution. Behavior of various hemodynamic indices]. / Emodiluizione intenzionale normovolemica spinta. Comportamento di alcuni indici emodinamici.

Changes in mixed venous oxygen saturation of hemoglobin (SvO2), heart rate (HR), cardiac index, (SI) were measured in 20 patients undergoing major orthopedic surgery (rachis and pelvis bone resections for tumours: mean-lasting 8 hours), to estimate the safety limits during isovolemic hemodilution. Up to Hb 8 g%, in all patients, a cardiac index improvement (+41%) was found, and this was mainly caused by an increase in stroke index (+31%). For 16 patients at Hb 6 g%, this improvement was present only in 44% and declined during further hemodilution. In all cases, CI was moderately lower than baseline value (-18%) this was caused by an important increase in HR (= 55%) partially compensating for by the fall in SI (-57%). The Authors conclude that, in patients under general anaesthesia, isovolemic hemodilution is safe up to Hb 8 g%. Below this value the left ventricular performance rapidly declines.

[Sodium naproxen in postoperative pain in orthopedics. Comparison of 2 different doses]. / Il naprossene sodico nel dolore postoperatorio in ortopedia. Confronto tra due differenti dosaggi.

In order to use etiopathogenetic criteria for the treatment of postsurgical pain, non-steroid anti-inflammatory drugs (NSAIDs) can be used rather than narcotic analgesics. These agents are often classified as peripherally acting analgesic drugs; nevertheless in the last years many pages have who showed a central supraspinal analgesic effect. Sodium naproxen is commonly used in the treatment of postoperative orthopedic pain because of its pharmacokinetic properties. The aim of this study was to evaluate the suitable dosage of sodium naproxen for post-surgical pain relief. Forty patients submitted to foot surgery were randomized into two groups of 20 patients each. At the end of surgery one group of patients (group I) received sodium naproxen 275 mg i.m.; the same dose was administered after 12 hours. A second group (group II) received sodium naproxen 550 mg i.m. at the same time intervals. Based on a Descriptive scale for algometric measurements, the results showed significant differences in analgesic activity for the two treatments. The best results (70% of patients with no pain or slight pain vs 20% of patients) were obtained in the group that received sodium naproxen at the higher dosage (p less than 0.001). No differences were observed in the incidence of side-effects in the two groups. These results are discussed.

The effects of glucose ingestion and fasting on plasma immunoreactive beta-endorphin, adrenocorticotropic hormone and cortisol in obese subjects.

It has been demonstrated that opioid peptides are involved in the stimulation of food intake in rats and that the circulating beta-endorphin levels are increased in genetically obese rodents. Therefore, to assess whether the changes in food intake may influence circulating beta-endorphin levels in obese subjects, plasma beta-endorphin, ACTH and cortisol concentrations were determined in obese patients after an oral glucose load and during a 7-day total starvation. Baseline plasma beta-endorphin concentrations were significantly higher in obese patients than in control normal-weight subjects, while ACTH and cortisol levels were similar in both groups. Plasma beta-endorphin, ACTH and cortisol concentrations were not affected by the ingestion of 75 g glucose, neither were plasma beta-endorphin concentrations modified during prolonged starvation. Moreover, the lack of nycthemeral variations in beta-endorphin levels, documented before and during starvation while plasma ACTH and cortisol were significantly reduced in the evening, suggests that some extra anterior pituitary sources or some obesity-related changes in beta-endorphin metabolism may contribute to the pool of circulating beta-endorphin in obese subjects. On the other hand, even the extreme changes in nutritional conditions, such as total food deprivation or glucose ingestion, are devoid of any detectable influence on circulating beta-endorphin levels.

[Total intravenous anesthesia with propofol vs. propofol/N2O anesthesia]. / Anestesia totalmente endovenosa con propofol vs anestesia propofol/N2O.

The authors have compared two groups of 31 patients each, undergone an anaesthesia with propofol-O2/N2O (group I) and propofol-O2/air (group II). The average anaesthetic dosage and the neuromuscular recovery time have been valued, keeping constant the dose of analgesic. The average consumption of propofol (except the inductive dose of 2 mg/kg) was 7.41 +/- 1.71 mg/kg/h in group I, and 7.47 +/- 1.76 in group II (p = 0.88; not significant) and the neuromuscular recovery time 56.12 +/- 34.55 m' and 49.48 +/- 40.50 m' respectively (p = 0.53; not significant). The cardiocirculatory parameters have been compared at the time of induction, surgical incision and for all the operation time, reporting every undesired effect. The awakening has been monitored until 15 m' from the interruption of propofol infusion. The data obtained don't permit to observe significant differences with regard to analgesia, neuromuscular block and awakening time. Therefore the authors put the question of the real necessity to use nitrous oxide, when it has utilized an efficient intravenous anaesthetic as the propofol has proved to be.

Production of interleukin 1 and tumour necrosis factor activities in bronchoalveolar washings following infection of mice by influenza virus.

Mice were infected with influenza A virus by aerosol. Bronchoalveolar washings obtained from infected mice contained interleukin 1 (IL-1) and tumour necrosis factor (TNF) activities. IL-1 was present at day 4 post-infection but not at day 7. TNF activity was present at day 4 and day 7 post-infection. The presence of both these monokines was coincident with increased cell populations in the lungs. In vitro studies demonstrated that macrophages from non-infected mice produce IL-1 and TNF activities in response to live influenza A virus stimulation. These results suggest that a direct interaction between virus and alveolar macrophages leads to IL-1 and TNF production during the course of infection and could account for both the immune responses and the pathology that occur during influenza A virus infection.

Immunological activities of RU-41740, a glycoprotein extract from Klebsiella pneumoniae. III. Role of LPS-like and LPS-non-related molecules.

RU-41740, a glycoprotein complex extracted from Klebsiella pneumoniae, is an immunomodulating agent which acts on B cells and macrophages. It has been shown that RU-41740 is composed mainly of two macromolecular fractions, F1, having an LPS-related structure, and P1, with a proteoglycan structure. In the present paper, the effects of these molecules on B cells and on IL-1 and tumour necrosis factor (TNF), production by macrophages were compared. Data reveal that both fractions were mitogenic for murine B cells and induced IL-1 and TNF production by macrophages. The LPS-like fraction (F1) was sensitive to polymyxin B and was unable to activate macrophages and spleen cells from LPS non-responder mice. The P1 fraction was mitogenic for B cells and induced the production of IL-1 and TNF activities by macrophages from LPS non-responder C3H/HeJ mice. The cytotoxic activity was due to TNF alpha, since treatment with anti-TNF alpha antiserum abrogated the lytic activity of supernatants from stimulated macrophages. The differences observed between P1 and F1 fractions in terms of sensitivity to polymyxin B and activity towards C3H/HeJ spleen cells and macrophages suggest that the two structurally distinct molecules isolated from RU-41740 could act at different sites on immunocompetent cells.