Eduard Havel

Pneumocystis pneumonia during medicamentous treatment of Cushing's syndrome--a description of two cases.

Only a few cases of pneumocystis pneumonia (PCP) in Cushings syndrome have been published in the literature so far. In the majority of these patients, the pneumonia occurred after reduction of the hypercortisolism with medicamentous treatment. We report two cases of PCP during conservative treatment of hypercortisolism. We describe clinical, imaging and laboratory findings in two patients and review published cases of pneumocystits pneumonia in Cushings syndrome. A 60-year-old woman and 20-year-old man with Cushings syndrome due to ectopic ACTH syndrome were treated at our department. Both developed pneumocystis pneumonia early after treatment with ketoconazole and ethomidate bromide had been introduced and the levels of cortisol rapidly decreased. PCP prophylaxis in patients with high cortisolemia should be started before treatment of hypercortisolism in current practice. Gradual lowering of plasma cortisol should also reduce the risk of infection by Pneumocystis jiroveci.

A pilot study on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving piperacillin/tazobactam.

BACKGROUND In critically ill patients, multi-trauma and intensive therapy can influence the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics with time-dependent bacterial killing. Consequently, PK/PD targets (%fT>MIC) - crucial for antimicrobial effects -may not be attained. METHODS Two patients admitted to the surgical ICU of the University Hospital in Hradec Králove for multiple-trauma were given piperacillin/tazobactam by 1-hour IV infusion 4/0.5 g every 8h. PK variables: total and renal clearance (CLtot, CLR), volume of distribution (Vd), and elimination half-life (T1/2) were calculated, followed by glomerular filtration rate (MDRD) and cumulative fluid balance (CFB-total fluid volume based on 24-h registered fluid intake minus output). The PK/PD target attainment (100%fT>MIC) was defined as free (f) piperacillin plasma concentrations that remain, during the entire dosing interval (T), above the minimum inhibitory concentration (100%fT>MIC) within days 4-8 (when CFB culminates and disappears). Piperacillin concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and corrected for unbound fraction (22%). RESULTS CFB culminated over days 2-5 reaching 15-30 L and was associated with a large Vd (29-42 L). While MDRD in patient 1 was low (0.3-0.4 mL s⁻¹ 1.7 m⁻²), that of patient 2 was increasing (> 3.1 mL s⁻¹ 1.7 m⁻²), which was associated with augmented CLR. In patient 2, the fT reached only 62, 52, and 44% on days 4, 6, and 8, respectively. In patient 1, the %fT was much higher, attaining values four to fivefold greater than that targeted. CONCLUSIONS Critically ill patients are at risk of drug under- or overdosing without dose up-titration with regard to covariate effects and individual drug pharmacokinetics.

Markers of Perioperative Bowel Complications in Colorectal Surgery Patients

Colorectal cancer is a clinical condition whose treatment often involves intestinal resection. Such treatment frequently results in two major gastrointestinal complications after surgery: anastomotic leakage and prolonged ileus. Anastomotic leakage is a serious complication which, more often than not, is diagnosed late; to date, C-reactive protein is the only available diagnostic marker. A monocentric, prospective, open case-control study was performed in patients (n = 117) undergoing colorectal surgery. Intestinal fatty acid binding protein (i-FABP), citrulline, D-lactate, exhaled hydrogen, Escherichia coli genomic DNA, and ischemia modified albumin (IMA) were determined preoperatively, postoperatively, and on the following four consecutive days. Bacterial DNA was not detected in any sample, and i-FABP and D-lactate lacked any distinct potential to detect postoperative bowel complications. Exhaled breath hydrogen content showed unacceptably low sensitivity. However, citrulline turned out to be a specific marker for prolonged ileus on postoperative days 3-4. Using a cut-off value of 20 μmol/L, a sensitivity and specificity of ~75% was achieved on postoperative day 4. IMA was found to be an efficient predictor of anastomosis leak by calculating the difference between preoperative and postoperative values. This test had 100% sensitivity and 80% specificity and 100% negative and 20% positive predictive value.

Extracorporeal LDL cholesterol elimination (25 years of experience in CZ)

In the Czech Republic the therapy of severe familial hypercholesterolemia (FH) by extracorporeal elimination using LDL-apheresis (immunoadsorption) and hemorheopheresis is concentrated into one center. The authors evaluate the long-term therapy (3-12 years, median 7,25) in 12 patients with FH - 3 homozygous, 9 heterozygous; Fredrickson type IIa, IIb (treated: 9 by LDL-apheresis and 3 by hemorheopheresis). Immunoapheretic interventions decrease LDL-cholesterol, ApoB and even Lp(a) by about 82 +/- 1; 73 +/- 13; 82 +/- 19 %, respectively. Selected non-invasive methods are important for a long-term and repeated follow-up. Carotid intima-media thickness showed improvement or stagnation in 75% of the patients. The level of some adhesive molecules, cytokines, endoglin and some coagulation functions were measured, but no universally accepted biomarkers informing of the actual activity of the disease were found to predict and plan the therapy. A program for procedure planning with the use of Microsoft® Excel for Windows® was developed. In summary, LDL-apheresis and hemorheopheresis substantially lower LDL-cholesterol in FH. Our experience with long-term therapy also shows good tolerance and a small number of complications (5,6% of clinically irrelevant side-effects). Hemorheopheresis may improve blood flow in microcirculation in familial hypercholesterolemia and also in some other disorders of microcirculation.

Interrelationship between fatty acid composition, lipid peroxidation and alpha-tocopherol consumption post-LDL-apheresis treatment evaluated by liquid chromatography and gas chromatography

Abstract The performance of regular low-density lipoprotein (LDL)-apheresis (LA) permits the achievement of lower levels of LDL-cholesterol (LDL-C) and the related apolipoprotein B-containing lipoproteins. Consequently, the application of LA may offer opportunities to study the influence of rapid changes of lipid homeostasis upon particular atherogenic species. The purpose of the study was to analyze the interrelationship between fatty acid composition, lipid peroxidation, and alpha-tocopherol consumption post-immuno-LA (Sepharose 4b columns carrying an anti-apoprotein B antibody) in six hyperlipidemic patients (three men and three women, age 14–56 years) by liquid chromatography (LC) and gas chromatography (GC). Immediately after LA, we observed significantly decreased serum thiobarbituric acid-reactive substances (TBARS) and serum total Vitamin E ( P P P P =0.07), and was decreased in high-density lipoprotein (HDL) ( P P =0.01) and decreased in LDL ( P P =0.02), and non-significantly increased in LDL ( P =0.08). Analysis of long-term effects of LA upon lipid metabolism revealed that Vitamin E in serum and lipoprotein fractions, neither serum TBARS did change significantly. Plasma phospholipids significantly decreased ( P P P

Energy, Protein, Carbohydrate, and Lipid Intakes and Their Effects on Morbidity and Mortality in Critically Ill Adult Patients: A Systematic Review

The guidelines for nutritional support in critically ill adult patients differ in various aspects. The optimal amount of energy and nutritional substrates supplied is important for reducing morbidity and mortality, but unfortunately this is not well known, because the topic is complex and every patient is individual. The aim of this review was to gather recent pertinent information concerning the nutritional support of critically ill patients in the intensive care unit (ICU) with respect to the energy, protein, carbohydrate, and lipid intakes and the effect of their specific utilization on morbidity and mortality. Enteral nutrition (EN) is generally recommended over parenteral nutrition (PN) and is beneficial when administered within 24-48 h after ICU admission. In contrast, early PN does not provide substantial advantages in terms of morbidity and mortality, and the time when it is safe and beneficial remains unclear. The most advantageous recommendation seems to be administration of a hypocaloric (<20 kcal · kg-1 · d-1), high-protein diet (amino acids at doses of ≥2 g · kg-1 · d-1), at least during the first week of critical illness. Another important factor for reducing morbidity is the maintenance of blood glucose concentrations at 120-150 mg/dL, which is accomplished with the use of insulin and lower doses of glucose of 1-2 g · kg-1 · d-1, because this prevents the risk of hypoglycemia and is associated with a better prognosis according to recent studies. A fat emulsion is used as a source of required calories because of insulin resistance in the majority of patients. In addition, lipid oxidation in these patients is ∼25% higher than in healthy subjects.

Integration of Endovascular Therapy of Ruptured Abdominal and Iliac Aneurysms in the Treatment Algorithm: A Single-Center Experience in a Medium-Volume Vascular Center

Purpose: To evaluate the influence of endovascular therapy of ruptured abdominal or iliac aneurysms on total mortality. Materials and Methods: We analyzed the mortality of 40 patients from 2005 to 2009, when only surgical treatment was available. These results were compared with the period 2010 to 2013, when endovascular aneurysm repair (EVAR) was assessed as the first option in selected patients. Results: During 2005 to 2009, the mortality was 37.5%. From 2010 to 2013, 45 patients were treated with mortality 28.9%. Open repair was performed in 35 (77.8%) patients and EVAR in 10 (22.2%) patients. The 30-day and 1-year mortality rates of the EVAR group were 0% and 20%, respectively, and the total mortality rate was 30% during follow-up (median 11 months, range 1-42 months). The 30-day mortality in the surgical group remained unchanged, at 37.1%, and 1-year and total mortality rates were 45.7% and 51.4%, respectively. Conclusion: Following integration in the treatment algorithm, EVAR decreased total mortality in our center by 8.6%.

Nonbacterial thrombotic endocarditis involving all four cardiac valves.

Nonbacterial thrombotic endocarditis (NBTE) is a well-known complication of hypercoagulable states, particularly in patients with malignancies. Its complications comprise thrombembolism rather than valvular dysfunction. We present a case of a 71-year-old man treated for colonic carcinoma, who died 1 month after tumor resection with clinical signs of respiratory failure. Ante mortem, there was no suspicion of cardiac disease. The autopsy revealed NBTE affecting all four cardiac valves simultaneously, as well as multiple systemic and pulmonary thrombemboli. Microscopically, neither microorganisms nor inflammation were found in the thrombi and/or valve tissues. To the best of our knowledge, this is the fourth case of quadri-valvular NBTE reported in the English-written literature so far.

Re: Pyoderma gangrenosum: an uncommon cause of septic shock

had a leucocytosis, and an abdominal ultrasound showed no free fluid. He subsequently underwent abdominal computed tomography (CT) imaging, which showed no free fluid or free gas, with the solitary finding of a markedly thickened appendiceal wall (10 mm) with adjacent fat stranding (see Fig. 1), consistent with an inflamed appendix. He underwent a diagnostic laparoscopy, which confirmed the clinical and radiological suspicion of acute appendicitis, and an appendicectomy was performed. He had an uneventful postoperative course and was discharged the next day. Histological examination confirmed an acutely inflamed appendix, but without an intraluminal faecolith. Blunt abdominal trauma and appendicitis are two of the most common presentations requiring surgical consultation in Australian emergency departments. While the trauma setting is not immediately conducive to consideration of this differential, acute traumatic appendicitis has been described, with animal studies confirming this mechanism of action. Ramsook et al. (2001) provided criteria for diagnosing post-traumatic appendicitis to differentiate patients with undiagnosed appendicitis incurring incidental abdominal trauma: absence of abdominal pain prior to trauma, time interval between injury and symptoms of 6–48 h, and the development of progressive abdominal symptoms leading to appendicectomy, with positive pathological findings. These factors were all confirmed in the current case.

Covariate determinants of effective dosing regimens for time-dependent beta-lactam antibiotics for critically ill patients

AIMS Critically ill patients undergoing aggressive fluid resuscitation and treated empirically with hydrosoluble time-dependent beta-lactam antibiotics are at risk for sub-therapeutic plasma concentrations. The aim of this study was to assess the impact of two covariates - creatinine clearance (Clcr) and cumulative fluid balance (CFB) on pharmacokinetics/pharmacodynamics (PK/PD) target attainment within a week of treatment with meropenem (ME) or piperacillin/tazobactam (PIP/TZB). METHODS In this prospective observational pharmacokinetic (PK) study, 18 critically ill patients admitted to a surgical Intensive Care Unit (ICU) were enrolled. The primary PK/PD target was free antibiotic concentrations above MIC at 100% of the dosing interval (100%fT>MIC) to obtain maximum bactericidal activity. Drug concentration was measured using liquid chromatography-tandem mass spectrometry. RESULTS The treatment of both 8 septic patients with IV extended ME dosing 2 g/3 h q8 h and 10 polytraumatized patients with IV intermittent PIP/TZB dosing 4.0/0.5 g q8 h was monitored. 8/18 patients (44%) manifested augmented renal clearence (ARC) where Clcr ≥130 mL/min/1.73 m2. Maximum changes were reported on days 2-3: the median positive CFB followed by the large median volume of distribution: Vdme=70.3 L (41.9-101.5), Vdpip = 46.8 L (39.7-60.0). 100%fTme>MIC was achieved in all patients on ME (aged ≥60 years), and only in two patients (non-ARC, aged ≥65 years) out of 10 on PIP/TZB. A mixed model analysis revealed positive relationship of CFBpip with Vdpip (P=0.021). CONCLUSION Assuming that the positive correlation between CFB and Vd exists for piperacillin in the setting of the pathological state, then CFB should predict Vdpip across subjects at each and every time point.