Candidemia in the intensive care unit: analysis of direct treatment costs and clinical outcome in patients treated with echinocandins or fluconazole.

Direct treatment costs caused by candidemia in German intensive care unit (ICU) patients are currently unknown. We analyzed treatment costs and the impact of antifungal drug choice. Comprehensive data of patients who had at least one episode of candidemia while staying in the ICU between 01/2005 and 12/2010 were documented in a database using the technology of the Cologne Cohort of Neutropenic Patients (CoCoNut). A detailed analysis of all disease-associated treatment costs was performed. Patients treated with echinocandins (i.e., anidulafungin, caspofungin, micafungin) or fluconazole were analyzed separately and compared. Forty-one and 64 patients received echinocandins and fluconazole, respectively. The mean Acute Physiology and Chronic Health Evaluation (APACHE) IV score was 114 (95 % confidence interval [CI]: 106-122) vs. 95 (95 % CI: 90-101, p = <0.001). Twenty-three (56 %) and 33 (52 %, p = 0.448) patients survived hospitalization, while 17 (41 %) and 22 (34 %, p = 0.574) survived one year after diagnosis. In the echinocandin and fluconazole groups, the mean costs per patient of ICU treatment were 20,338 (95 % CI: 12,893-27,883) vs. 11,932 (95 % CI: 8,016-15,849, p = 0.110), and the total direct treatment costs per patient were 37,995 (95 % CI: 26,614-49,376) vs. 22,305 (95 % CI: 16,817-27,793, p = 0.012), resulting in daily costs per patient of 1,158 (95 % CI: 1,036-1,280) vs. 927 (95 % CI: 828-1,026, p = 0.001). Our health economic analysis shows the high treatment costs of patients with candidemia in the ICU. Sicker patients had a prolonged hospitalization and were more likely to receive echinocandins, leading to higher treatment costs. Outcomes were comparable to those achieved in less sick patients with fluconazole.

Observations on the effects of inhaled isoflurane in long-term sedation of critically Ill children using a modified AnaConDa©-system.

Long-term intravenous sedation may present problems due to dependence and side effects. Medical records of children who were administered isoflurane were reviewed. 15 patients (9 boys, 6 girls) with a mean age of 11.8 month (+2.4) were analysed.Analgesia and sedation was given in mean 9.7+1.1 days before commencing inhalation using a modified application device (AnaConDa©). Administration was given over a period of 7.2+1.4 days. Depth of sedation was monitored by using Comfort- and Hartwig-scores. Observations included continuous monitoring of heart-rate, pulse oxymetry, blood pressure and cerebral tissue oxygenation.Within 4 h post administration of isoflurane a satisfactory increase in the depth of sedation was seen and kept till extubation. 6/15 patients received tracheostomies during the observation period. None of the patients observed suffered life-critical events of the modified application of isoflurane proceeded without complications. Ketamine and clonidine infusion rates were significantly reduced (p<0.005) as well as the use and overall infusion rate of midazolam, γ-hydroxy butyrate, fentanyl and morphine (p<0.05).Isoflurane inhalation may provide an additional option for long-term sedation in a specific group of critically ill infants but neurodegenerative toxic effects will have to be taken into account when using volatile anesthetics at any time during infancy.

Hemolytic anemia and methemoglobinemia in a preterm baby as a complication of antenatal intraamnial injection of toluidine blue.

A late preterm infant was born 4.5 h after intraamniotic injection of 90 mg of Toluidine blue to confirm premature rupture of membranes. Due to the fetal exposition to the dye, the entire body of the patient was blue stained and the baby suffered from methemoglobinemia, Heinz' body positive hemolytic anemia and hyperbilirubinaemia requiring exchange transfusion. These complications underline that antenatal exposition of toluidine blue may result in considerable postnatal infant morbidity. Therefore intraamniotic application of toluidine blue should be discouraged.

[Primary ciliary dyskinesia causing neonatal respiratory distress]. / Primäre Ziliendyskinesie als Ursache neonataler Atemnot.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a hereditary disorder of structure and function of the cilia of respiratory epithelium of the upper and lower airways. Prevalence is estimated with 1:15 000 to 1:30 000 births. We present a newborn infant with respiratory distress caused by PCD. PATIENT: On the first day of life, the male newborn developed dyspnoe and cyanosis, so that CPAP and short term ventilation was necessary. Varying atelectasis impressed on the chest radiographs and the diagnosis of PCD was made by nasal brush biopsies. Causative is a lack of the inner dynein arms of the cilia. The clinical features of newborns with the diagnoses of PCD are listed and compared with the own case. CONCLUSION: PCD is a rare cause of neonatal respiratory distress and should be considered in term infants with unknown and prolonged course even if Situs inversus is lacking.

[Smith-Lemli-Opitz syndrome--case report, diagnostics and therapeutic options]. / Das Smith-Lemli-Opitz Syndrom--Fallbericht, Diagnostik, therapeutische Optionen.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal-recessive disease characterised by the combination of (foetal) growth retardation, mental retardation and a typical malformation pattern. In particular, the combination of cardiovascular defects, Y-shaped syndactyly of the 2 (nd) and 3 (rd) toes and a distinctive craniofacial appearance, often including a cleft palate, are characteristic of SLOS. The disease is caused by a defect in cholesterol synthesis resulting in a reduced or absent activity of the enzyme 7-dehydrocholesterol reductase (DHCR7). As a consequence, a lack of cholesterol and an increase of toxic cholesterol precursors are observed in the majority of patients. We report on a female patient who was born at 37 weeks of gestation and was both small and light for gestational age who displayed typical signs of SLOS. After the diagnosis had been confirmed, a therapeutic approach with oral substitution of cholesterol and the administration of simvastatin was initiated. In spite of this strategy, the patient died at the age of 12 weeks from the disease. Based on the case presented, we review and discuss current diagnostic and therapeutic options for patients with SLOS.

A 12-year-old boy with fatal hemolytic-uremic-syndrome, excessive neutrophilia and elevated endogenous granulocyte-colony-stimulating-factor serum concentrations.

We report the case of a 12-year-old boy with fatal enteropathic hemolytic-uremic syndrome who developed excessive neutrophilia in the course of his disease, his leukocyte count exceeding 200,000/mm3. Neutrophilia, as it was observed in this case, is an extreme manifestation of a phenomenon, that is commonly observed in hemolytic-uremic syndrome [Salzmann et al. 1991]. Neutrophilia is suspected to be correlated with a bad prognosis [Walters et al. 1989], but further explanation of this phenomenon is needed. Other underlying diseases related with neutrophilia, especially hematologic malignancies, could be ruled out by far. We examined endogenous G-CSF serum concentrations of the HUS patient from day 6 to 13 in the course of the disease. The assayed concentrations were found to be elevated in the first two samples taken (peak level 340 pg/ml). In the samples taken after plasmapheresis had started, G-CSF concentrations were not found to be elevated. The peak of neutrophilia was reached short before death on day 13 of the disease. We also measured the serum G-CSF concentrations of 28 children aged 3 months to 12 years, who were treated with various infectious and noninfectious diseases in our hospital. In none of the examined samples was there a G-CSF serum concentration exceeding 50 pg/ml. The reported case shows evidence that the commonly observed coincidence of leukocytosis and HUS may reflect the role of G-CSF (and other cytokines) in the inflammatory process underlying the HUS.

A prospective, randomized, multicenter trial of high-frequency oscillatory ventilation compared with conventional ventilation in preterm infants with respiratory distress syndrome receiving surfactant.

OBJECTIVES: To compare high-frequency oscillatory ventilation (HFOV) and intermittent positive pressure ventilation (IPPV) as a primary ventilation mode in preterm infants with respiratory distress syndrome. Primary end points were survival and maintenance of the randomized ventilation mode. STUDY DESIGN: Prospective, multicenter, randomized clinical trial. SETTING: Level III neonatal intensive care units at three university children's hospitals. PATIENTS: Ninety-six premature infants (gestational age < 32 weeks) randomly assigned to HFOV or IPPV within the first 2 hours of life. All patients received a natural surfactant. No differences were found between the study groups with respect to the demographic data or the severity of respiratory distress syndrome. Infants were stratified at randomization, by birth weight, into two groups: 750 to 1000 gm (n = 32) and 1001 to 1500 gm (n = 64). The centers involved complied with a study protocol that planned a reduction in respiratory pressures when the infant's oxygen requirement had reached a fractional concentration of inspired oxygen of 0.6. RESULTS: Five patients in the HFOV group died, and eight patients did not respond to the randomized ventilation mode; whereas four patients in the IPPV group died, and nine were switched to HFOV. No differences were found in gas exchange or ventilator support over the first 72 hours. Premature infants with a birth weight < 1000 gm had a significantly shorter course to reach fractional concentration of inspired oxygen of 0.21 while receiving IPPV than those receiving HFOV (9.3+/-4.5 days vs 27.5+/-10.2 days, p = 0.01). No differences were found between the groups in extraalveolar air (HFOV seven; IPPV, seven) and intracranial bleeding (HFOV, nine; IPPV, eight). CONCLUSION: After surfactant treatment, HFOV, as a primary ventilation mode in premature infants with respiratory distress syndrome, is as safe and efficacious as conventional ventilation.

A staged protocol for the treatment of persistent pulmonary hypertension of the newborn.

The purpose of this report is to propose a staged therapeutic protocol for the treatment of persistent pulmonary hypertension of the newborn (PPHN) based on retrospective clinical experience. We analysed the clinical course of 19 term and near-term neonates with severe PPHN treated between 1991 and 1993, before the introduction of inhalational nitric oxide (NO) therapy. Basic therapy consisted of continuous sedation, and analgesia, circulatory support with dobutamine, dopamine and substitution of 5% albumin or packed red blood cells, mechanical hyperventilation, alkalisation with sodium bicarbonate and surfactant instillation. Consecutive therapy included the administration of norepinephrine, high frequency oscillatory ventilation (HFOV), Prostacyclin (PGI2) and extracorporeal membrane oxygenator (ECMO) therapy with entry criteria for each stage of treatment. From our observations we suggest that firstly, an early increase in systemic mean arterial pressure due to norepinephrine and secondly, HFOV trials are beneficial in patients with PPHN. The staged protocol shall be applicable in most neonatal intensive care units in which inhalational NO and ECMO therapies are not available and includes our present entry criteria for both therapies.

Neonatal haemochromatosis: report of a patient with favourable outcome.

UNLABELLED: A male newborn was referred on the 2nd day of life because of suspected sepsis. The child became comatose and ventilator dependent owing to progressive hepatic failure with hyperammonaemia. Diagnostic studies revealed an highly elevated ferritin level. The family history was remarkable in that an aunt and a great aunt on his mother's side have idiopathic haemochromatosis. Open liver biopsy showed advanced cirrhosis with cholestasis and excessive hepatocellular siderosis. Concentrations of iron in liver tissue were highly elevated. The child's status improved unexpectedly, and excretory and synthetic liver function gradually returned to normal. CONCLUSION: Neonatal haemochromatosis is not an irreversible disease of iron metabolism but rather a distinct outcome of fetal liver disease which predisposes by an yet unknown mechanism to a derangement of fetoplacental iron handling. If patients survive the initial phase of liver failure, prognosis is largely dependent upon liver cirrhosis and its sequels. The iron overload in this type of haemochromatosis is reversible and not progressive.

Renal tubular dysgenesis: a report of two cases.

Renal tubular dysgenesis, a congenital disorder of renal tubular development, was diagnosed in two newborns with oligohydramnios and Potter phenotype. Renal tubular dysgenesis (RTD) is a recently recognized congenital disorder of renal tubular development associated with oligohydramnios, Potter phenotype, and neonatal respiratory and renal failure. We report two newborn siblings with typical clinical and anatomic features of RTD. The diagnosis was proven by autopsy in one child. The pediatrician should consider the diagnosis of RTD in a child with congenital anuria and structurally normal kidneys on ultrasound, especially if a maternal history of late trimester oligohydramnios is present.

Clinical experiences with high-frequency oscillatory ventilation in newborns with severe respiratory distress syndrome.

OBJECTIVE: To generate hypotheses about which subgroups of newborns with severe respiratory distress syndrome might benefit most from high-frequency oscillatory ventilation. DESIGN: Retrospective analysis of a case series of newborns with severe respiratory distress syndrome who were treated in our department with high-frequency oscillatory ventilation. SETTING: Referral center for neonatal and pediatric intensive care medicine. PATIENTS: All newborns (n = 18), admitted between June 1991 and February 1993, of various gestational ages (26 to 41 wks), with severe respiratory distress syndrome caused by various underlying pulmonary diseases who did not respond to conventional therapy and who thus were treated with high-frequency oscillatory ventilation. MAIN OUTCOME MEASURES: Survival until discharge from our unit and persistent improvement of gas exchange. RESULTS: Eight (44%) of 18 patients survived; ten (55%) patients died. Four (22%) survivors showed marked clinical improvement with the initiation of high-frequency oscillatory ventilation. Four (22%) survivors did not respond to high-frequency oscillatory ventilation. The responder group consisted of term or near-term neonates (gestational age at least 35 wks) with pulmonary disease that was complicated by persistent pulmonary hypertension. The group of premature neonates with a gestational age of < 35 wks did not respond to high-frequency oscillatory ventilation. CONCLUSIONS: As a result of our analysis, we hypothesize that term newborns with severe respiratory distress syndrome complicated by persistent pulmonary hypertension and hypercarbia can benefit from high-frequency oscillatory ventilation. Premature neonates with ventilation-induced lung injury are not likely to respond to high-frequency oscillatory ventilation.

[Radical treatment and prognosis: results of a multicenter surgical-pathologic TNM stomach cancer study]. / Radikalität und Prognose: Ergebnisse der multizentrischen chirurgisch-pathologischen Magencarcinom-TNM-Studie.

A multicentre observational study with 22 departments of surgery and 14 departments of pathology was started on April 1st, 1982 to validate TNM classification for patients with gastric carcinoma. 1417 patients with histologically proven gastric cancer entered the study. Follow-up is now 3-5 years. A subgroup of 138 patients (age under 65 years, no metastases M 0, curative resection R 0, only T 2-T 4-carcinomas and tumors situated only in the middle and lower third of the stomach) was studied. 65 had subtotal, 73 total resection. The 3 to 5 years cumulative survival time was at least not worse with subtotal in comparison to total resection.

[Criteria for biostatistical assessment in surgery of stomach cancer]. / Kriterien zur Biostatistik bei der Chirurgie des Magencarcinoms.

The problem of making valid statements about the prognosis of survival after radical operation of stomach cancer, based on retrospective or prospective studies, is investigated. Some explanations are given for contradictory or non-reproducible results in different subgroups. Especially the problem of searching for "significant" results by multiple testing of different subgroups (data snooping) is treated critically. In case of remaining open questions randomised studies appear to be inevitable.