Early diagnosis of invasive candidiasis with mannan antigenemia and antimannan antibodies.

Late treatment of invasive candidiasis (IC) results in severe complications and high mortality. New tools are needed for early diagnosis. We conducted a retrospective study to assess the diagnostic utility of mannan antigenemia (Mn) and antimannan antibodies (anti-Mn) in neutropenic cancer patients at high risk for candidiasis. Twenty-eight patients with IC (based on European Organization for Research and Treatment of Cancer and Mycoses Study Group definitions) and 25 controls were studied. Mn and anti-Mn were positive (> or = 0.25 ng/mL and > or = 5 AU/mL, respectively) in 25/28 (89%) patients with candidiasis and in 4/25 (16%) controls: sensitivity, 89%; specificity, 84%; positive predictive value, 86%; negative predictive value, 88%. In patients with hepatosplenic lesions, assessing Mn/anti-Mn shortened the median time of diagnosis of candidiasis when compared with imaging (9 versus 25 days after fever onset as first sign of infection; P < 0.001). Candidiasis was diagnosed before neutrophil recovery in 78% and 11% of cases with Mn/anti-Mn and radiology, respectively (P < 0.001). Mn and anti-Mn may be useful for early noninvasive diagnosis of IC.

Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): a multicenter study.

Myelodysplastic syndromes (MDS) with del(5q) are considered to have a benign course of the disease. In order to address the issue of the propensity of those patients to progress to acute myeloid leukemia (AML), data on 381 untreated patients with MDS and del(5q) characterized by low or intermediate I International Prognostic Scoring System (IPSS) risk score were collected from nine centers and registries. Median survival of the entire group was 74 months. Transfusion-dependent patients had a median survival of 44 months vs 97 months for transfusion-independent patients (P<0.0001). Transfusion need at diagnosis was the most important patient characteristic for survival. Of the 381 patients, 48 (12.6%) progressed to AML. The cumulative progression rate calculated using the Kaplan-Meier method was 4.9% at 2 years and 17.6% at 5 years. Factors associated with the risk of AML transformation were high-risk World Health Organization adapted Prognostic Scoring System (WPSS) score, marrow blast count >5% and red-cell transfusion dependency at diagnosis. In conclusion, patients with MDS and del(5q) are facing a considerable risk of AML transformation. More detailed cytogenetic and molecular studies may help to identify the patients at risk of progression.

Watching television: a previously unrecognized powerful trigger of λ waves.

OBJECTIVE: To assess whether lambda waves are elicited by watching television (TV) and their association with demographical and EEG features. METHODS: We retrospectively compared lambda wave occurrence in prolonged EEG monitorings of outpatients who were allowed to watch TV and in standard EEGs recorded in TV-free rooms. All EEGs were interpreted by the same two electroencephalographers. RESULTS: Of 2,072 standard EEG reports, 36 (1.7 %) mentioned lambda waves versus 46 (32.2%) of 143 prolonged EEG monitoring reports (P < 0.001). Multivariable comparison of prolonged EEG monitorings and standard EEGs disclosed that recordings performed in rooms with a TV (odds ratio, 20.6; 95% confidence interval, 4.8-88.0) and normal EEGs (odds ratio, 3.03; 95% confidence interval, 1.5-6.25) were independently associated with lambda waves. In the prolonged EEG monitoring group, all recordings with lambda waves also had positive occipital sharp transients of sleep. CONCLUSIONS: Watching TV likely represents a powerful and previously unrecognized stimulus for lambda waves. Furthermore, this study confirms the benign nature of this EEG variant and its strong association with positive occipital sharp transients of sleep.

Portal vein embolization with N-butyl cyanoacrylate before partial hepatectomy in patients with hepatocellular carcinoma and underlying cirrhosis or advanced fibrosis.

PURPOSE: To describe the safety, complications, and liver regeneration associated with the left liver after embolization of the right portal vein (PV) in patients with hepatocellular carcinoma (HCC) developed in the setting of advanced liver fibrosis and cirrhosis. MATERIALS AND METHODS: Forty patients (31 men, nine women; mean age, 62 years) with HCC underwent PV embolization over a 4-year period. Embolization was performed from a left PV percutaneous access with use of n-butyl cyanoacrylate (NBCA) mixed with iodized oil. Computed tomography (CT) volumetry was performed before and 1 month after PV embolization to measure the left lobe volume as well as the functional liver ratio defined by the ratio between the left lobe and the total liver volume minus tumoral volume. PV pressure and liver enzyme levels were compared before and 1 month after the procedure and complications were registered. Factors potentially affecting regeneration (age, sex, diabetes, chemoembolization, functional liver ratio before PV embolization, and Knodell histologic score) were evaluated by one-way and stepwise regression analysis. RESULTS: PV embolization could be achieved successfully in all cases. Two patients had partial PV thrombosis on the 1-month follow-up CT and two patients developed transient ascites after PV embolization. The left lobe volume increase was 41% +/- 32% after PV embolization and the functional liver ratio increased from 28% +/- 10% to 36% +/- 10% (P < .0001). Hypertrophy of the left lobe was greater in patients with a low functional liver ratio before PV embolization and those with an F3 fibrosis score. Other factors had no influence on left lobe regeneration. CONCLUSION: PV embolization with use of NBCA is feasible in patients with advanced fibrosis and cirrhosis. Hypertrophy of the left lobe of the liver after PV embolization has a statistically significant correlation with lower functional liver ratio and lower degrees of fibrosis.

Magnetic resonance cholangiography features of biliary abnormalities due to cavernous transformation of the portal vein.

BACKGROUND: The aim of this retrospective and monocentric study was to describe the magnetic resonance cholangiography (MRC) features of biliary abnormalities related to extrahepatic obstruction of the portal vein (EHOPV). METHODS: From September 2001 to May 2003, MRC was performed in 10 consecutive patients who had a portal thrombosis. RESULTS: Biliary ductal pathology was demonstrated via MRC in nine patients. It consisted of stenoses, ductal narrowing or irregularities involving the common bile duct for three patients with extrahepatic portal vein thrombosis discovered a mean of 1.5 years ago, or involving both right and left intrahepatic bile ducts and common bile duct for six patients with extrahepatic portal vein thrombosis discovered a mean of 16.2 years ago. Dilation of intrahepatic bile ducts was seen for seven patients, four of them having cholestasis. For three patients with symptomatic cholestasis, direct cholangiography (DC) was performed and showed the same findings as MRC which nevertheless overestimated the degree of bile duct stenosis. CONCLUSIONS: MRC seems to constitute an accurate tool to investigate noninvasively patients with portal biliopathy.

Leukemic cluster growth in culture is an independent risk factor for acute myeloid leukemia and short survival in patients with myelodysplastic syndrome.

In patients with myelodysplastic syndrome (MDS) precursor cell cultures (colony-forming unit cells, CFU-C) can provide an insight into the growth potential of malignant myeloid cells. In a retrospective single-center study of 73 untreated MDS patients we assessed whether CFU-C growth patterns were of prognostic value in addition to established criteria. Abnormalities were classified as qualitative (i.e. leukemic cluster growth) or quantitative (i.e. strongly reduced/absent growth). Thirty-nine patients (53%) showed leukemic growth, 26 patients (36%) had strongly reduced/absent colony growth, and 12 patients showed both. In a univariate analysis the presence of leukemic growth was associated with strongly reduced survival (at 10 years 4 vs. 34%, p = 0.004), and a high incidence of transformation to AML (76 vs. 32%, p = 0.01). Multivariate analysis identified leukemic growth as a strong and independent predictor of early death (relative risk 2.12, p = 0.03) and transformation to AML (relative risk 2.63, p = 0.04). Quantitative abnormalities had no significant impact on the disease course. CFU-C assays have a significant predictive value in addition to established prognostic factors in MDS. Leukemic growth identifies a subpopulation of MDS patients with poor prognosis.

Estimating the incidence of cancers in Switzerland: 1983-1987.

Estimates have recently been made of the incidence of cancers in the countries of the European Community. Similar estimates are given for Switzerland, based on data from the six Swiss cantonal cancer registries, all of which have been operating for at least 12 years. These registries cover Basel, Geneva, Neuchatel, St Gall and Appenzell, Vaud and Zurich, which account for about 50% of the Swiss population as a whole. Two different methods were used to extrapolate from the incidences observed in the regions covered by cancer registration to the entire country. The first method is based solely on the distribution of populations according to the country's main linguistic groups, whereas the second relies on mortality data. Estimates obtained by the second approach are presented and their reliability is discussed. Comparison of the age incidence curve with that of Denmark tends to confirm the validity of the estimations. Estimated standardised rates (world population) for all sites except nonmelanomatous skin cancer are 294.3 for males and 214.2 for females. Comparisons with other European countries show that in males, lung cancer is relatively less common in Switzerland, whereas in females, breast cancer is relatively more frequent.

Isolated congenital atrioventricular block diagnosed in utero: natural history and outcome.

BACKGROUND: Isolated congenital atrioventricular block (CAVB) diagnosed in utero is associated with a high morbidity and mortality. Prognosis is especially poor when heart rate drops below 55 beats per minute (bpm) and when fetal hydrops develops. We describe the natural history and outcome of 24 infants with isolated CAVB diagnosed in utero, review the literature, and assess the risk factors that could predict outcome. METHODS: This was a retrospective multicenter study of 24 patients with isolated CAVB diagnosed in utero. RESULTS: CAVB was detected at a mean gestational age (GA) of 24.7 +/- 5.1 weeks. Ten fetuses initially presented with complete heart block. Low heart rate or incomplete heart block was the first documentation of bradyarrhythmia in the other 14 fetuses. In 11 of them, CAVB developed during pregnancy after a median time of 3 (range 1-16) weeks. Fetal hydrops developed in 10 of 24 (42%) fetuses at a mean GA of 27.6 +/- 5.1 weeks. Hydropic fetuses showed lower heart rates during pregnancy (47 +/- 10 bpm) than non-hydropic fetuses (57 +/- 10 bpm). There were three intrauterine deaths; all were hydropic and female. Nine viable females and 12 males were born at a mean GA of 37.1 +/- 6.1 weeks with an average birth weight of 3097 +/- 852 g. Fifteen CAVB patients required pacemaker (PM) intervention, 10 of them immediately after birth. Dilated cardiomyopathy (DCM) developed in three infants of whom two died of congestive heart failure, shortly after the diagnosis was made; one is still alive. Mortality before or after birth was 21%, and was associated with heart rates below 50 bpm and development of fetal hydrops. Poor outcome, defined as death, PM implantation, or development of DCM, occurred in 83% of cases and was associated with heart rates below 60 bpm during pregnancy. CONCLUSIONS: Isolated CAVB diagnosed in utero is associated with high morbidity and mortality. Patients who develop fetal hydrops show lower heart rates during pregnancy than patients who do not. A fetal heart rate below 50 bpm and development of fetal hydrops is associated with increased mortality. Rates below 60 bpm are associated with PM requirement and/or DCM.

Number of transferred embryos: how to reduce multiple pregnancies.

Because the diagnostic tools for predicting whether an early cleavage stage embryo can lead to a viable pregnancy are still elusive, transfer of more than one embryo remains quite common. However, the only way to reduce multiple pregnancies, considered as the main adverse effect of assisted reproductive technology, is to transfer a single embryo. In countries such as Switzerland and Germany, the law allows cryopreservation only at the 2-pronuclear stage. This restricts considerably the possibility of selecting the embryos to be transferred. Therefore, a good cryopreservation program at the 2-pronuclear stage is an essential tool to optimize the efficiency of in vitro fertilization (IVF). We therefore recommend the Cumulated Singleton Delivery Rate (CUSIDERA) as a measure of standard IVF efficiency. This rate averages approximately 23.5% when calculated over the last 10 years in our unit and reaches a value above 35% for patients with more than 10 zygotes. Elective single-embryo transfers and the decrease of iatrogenic multiple pregnancies in IVF remain dependent on better prognostic tools for the appropriate selection of patients, gametes, and zygotes.

HIV-1 reverse transcriptase connection domain mutations: dynamics of emergence and implications for success of combination antiretroviral therapy.

BACKGROUND: Factors promoting the emergence of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) connection domain mutations and their effect on antiretroviral therapy (ART) are still largely undetermined. We investigated this matter by analyzing genotypic resistance tests covering 400 amino acid positions in the RT of HIV-1 subtype B viruses and corresponding treatment histories and laboratory measurements. METHODS: The emergence of connection domain mutations was studied in 334 patients receiving monotherapy or dual therapy with thymidine analogues at the time of the genotypic resistance test. Response to subsequent combination ART (cART) was analyzed using Cox regression for 291 patients receiving unboosted protease inhibitors. Response was defined by ever reaching an HIV RNA level <50 copies/mL during the first cART. RESULTS: The connection domain mutations N348I, R356K, R358K, A360V, and A371V were more frequently observed in ART-exposed than ART-naive patients, of which only N348I and A360V were nonpolymorphic (with a prevalence of <1.5% in untreated patients). N348I correlated with M184V and predominantly occurred in patients receiving lamivudine and zidovudine concomitantly. A360V was not associated with specific drug combinations and was found to emerge later than M184V or thymidine analogue mutations. Nonpolymorphic connection domain mutations were rarely detected in the absence of established drug resistance mutations in ART-exposed individuals (prevalence, <1%). None of the 5 connection domain mutations associated with treatment showed a statistically significant effect on response to cART. CONCLUSIONS: Despite their frequent emergence, connection domain mutations did not show large detrimental effects on response to cART. Currently, routine implementation of connection domain sequencing seems unnecessary for developed health care settings.

Referral patterns and outcomes in noncritically ill patients with hospital-acquired acute kidney injury.

Background and objectives Despite modern treatment, the case fatality rate of hospital-acquired acute kidney injury (HA-AKI) is still high. We retrospectively described the prevalence and the outcome of HA-AKI without nephrology referral (nrHA-AKI) and late referred HA-AKI patients to nephrologists (lrHA-AKI) compared with early referral patients (erHA-AKI) with respect to renal function recovery, renal replacement therapy (RRT) requirement, and in-hospital mortality of HA-AKI. Design, setting, participants, & measurements Noncritically ill patients admitted to the tertiary care academic center of Lausanne, Switzerland, between 2004 and 2008 in the medical and surgical services were included. Acute kidney injury was defined using the Acute Kidney Injury Network (AKIN) classification. Results During 5 years, 4296 patients (4.12% of admissions) experienced 4727 episodes of HA-AKI during their hospital stay. The mean ± SD age of the patients was 61 ± 15 years with a 55% male predominance. There were 958 patients with nrHA-AKI (22.3%) and 2504 patients with lrHA-AKI (58.3%). RRT was required in 31% of the patients with lrHA-AKI compared with 24% of the patients with erHA-AKI. In the multiple risk factor analysis, compared with erHA-AKI, nrHA-AKI and lrHA-AKI were significantly associated with worse renal outcome and higher in-hospital mortality. Conclusions These data suggest that HA-AKI is frequent and the patients with nrHA-AKI or lrHA-AKI are at increased risk for in-hospital morbidity and mortality.

Health problems among detainees in Switzerland: a study using the ICPC-2 classification.

BACKGROUND: Little is known about the health status of prisoners in Switzerland. The aim of this study was to provide a detailed description of the health problems presented by detainees in Switzerland's largest remand prison. METHODS: In this retrospective cross-sectional study we reviewed the health records of all detainees leaving Switzerland's largest remand prison in 2007. The health problems were coded using the International Classification for Primary Care (ICPC-2). Analyses were descriptive, stratified by gender. RESULTS: A total of 2195 health records were reviewed. Mean age was 29.5 years (SD 9.5); 95% were male; 87.8% were migrants. Mean length of stay was 80 days (SD 160). Illicit drug use (40.2%) and mental health problems (32.6%) were frequent, but most of these detainees (57.6%) had more generic primary care problems, such as skin (27.0%), infectious diseases (23.5%), musculoskeletal (19.2%), injury related (18.3%), digestive (15.0%) or respiratory problems (14.0%). Furthermore, 7.9% reported exposure to violence during arrest by the police. CONCLUSION: Morbidity is high in this young, predominantly male population of detainees, in particular in relation to substance abuse. Other health problems more commonly seen in general practice are also frequent. These findings support the further development of coordinated primary care and mental health services within detention centers.

Mandibular osteoradionecrosis in squamous cell carcinoma of the oral cavity and oropharynx: incidence and risk factors.

Objective. Mandibular osteoradionecrosis (ORN) is a serious complication of radiotherapy (RT) in head and neck cancer patients. The aim of this study was to analyze the incidence of and risk factors for mandibular ORN in squamous cell carcinoma (SCC) of the oral cavity and oropharynx.Study Design. Case series with chart review.Setting. University tertiary care center for head and neck oncology.Subjects and Methods. Seventy-three patients treated for stage I to IV SCC of the oral cavity and oropharynx between 2000 and 2007, with a minimum follow-up of 2 years, were included in the study. Treatment modalities included both RT with curative intent and adjuvant RT following tumor surgery. The log-rank test and Cox model were used for univariate and multivariate analyses.Results. The incidence of mandibular ORN was 40% at 5 years. Using univariate analysis, the following risk factors were identified: oral cavity tumors (P < .01), bone invasion (P < .02), any surgery prior to RT (P < .04), and bone surgery (P < .0001). By multivariate analysis, mandibular surgery proved to be the most important risk factor and the only one reaching statistical significance (P < .0002).Conclusion. Mandibular ORN is a frequent long-term complication of RT for oral cavity and oropharynx cancers. Mandibular surgery before irradiation is the only independent risk factor. These aspects must be considered when planning treatment for these tumors.

Electroencephalogram changes during inhalation with nitric oxide in the pediatric intensive care patient--a preliminary report.

OBJECTIVES: Although endogenous nitric oxide (NO) is an excitatory mediator in the central nervous system, inhaled NO is not considered to cause neurologic side effects because of its short half-life. This study was motivated by a recent case report about neurologic symptoms and our own observation of severe electroencephalogram (EEG) abnormalities during NO inhalation. DESIGN: Blind, retrospective analyses of EEGs which were registered before, during, and after NO inhalation. EEG was classified in a 5-point rating system by an independent electroencephalographer who was blinded to the patients' clinical histories. Comparisons were made with the previous evaluation documented at recording. Other EEG-influencing parameters such as oxygen saturation, hemodynamics, electrolytes, and pH were evaluated. SETTING: Pediatric intensive care unit of a tertiary care university children's hospital. PATIENTS: Eleven ventilated, long-term paralyzed, sedated children (1 mo to 14 yrs) who had EEG or clinical assessment before NO treatment and EEG during NO inhalation. They were divided into two groups according to the NO-indication (e.g., congenital heart defect, acute respiratory distress syndrome). MEASUREMENTS AND MAIN RESULTS: All 11 patients had an abnormal EEG during NO inhalation. EEG-controls without NO showed remarkable improvement. EEG abnormalities were background slowing, low voltage, suppression burst (n = 2), and sharp waves (n = 2) independent of patients' age, NO-indication, and other EEG-influencing parameters. CONCLUSIONS: These preliminary data suggest the occurrence of EEG-abnormalities after application of inhaled NO in critically ill children. We found no correlation with other potential EEG-influencing parameters, although clinical state, medication, or hypoxemia might contribute. Comprehensive, prospective, clinical assessment regarding a causal relationship between NO-inhalation and EEG-abnormalities and their clinical importance is needed.

A prediction rule to identify low-risk patients with pulmonary embolism.

BACKGROUND: A simple prognostic model could help identify patients with pulmonary embolism who are at low risk of death and are candidates for outpatient treatment. METHODS: We randomly allocated 15,531 retrospectively identified inpatients who had a discharge diagnosis of pulmonary embolism from 186 Pennsylvania hospitals to derivation (67%) and internal validation (33%) samples. We derived our rule to predict 30-day mortality using classification tree analysis and patient data routinely available at initial examination as potential predictor variables. We used data from a European prospective study to externally validate the rule among 221 inpatients with pulmonary embolism. We determined mortality and nonfatal adverse medical outcomes across derivation and validation samples. RESULTS: Our final model consisted of 10 patient factors (age > or = 70 years; history of cancer, heart failure, chronic lung disease, chronic renal disease, and cerebrovascular disease; and clinical variables of pulse rate > or = 110 beats/min, systolic blood pressure < 100 mm Hg, altered mental status, and arterial oxygen saturation < 90%). Patients with none of these factors were defined as low risk. The 30-day mortality rates for low-risk patients were 0.6%, 1.5%, and 0% in the derivation, internal validation, and external validation samples, respectively. The rates of nonfatal adverse medical outcomes were less than 1% among low-risk patients across all study samples. CONCLUSIONS: This simple prediction rule accurately identifies patients with pulmonary embolism who are at low risk of short-term mortality and other adverse medical outcomes. Prospective validation of this rule is important before its implementation as a decision aid for outpatient treatment.