S100B in cardiac surgery brain monitoring: friend or foe?

Recent advances in perioperative management of adult and pediatric patients requiring open heart surgery (OHS) and cardiopulmonary bypass (CPB) for cardiac and/or congenital heart diseases repair allowed a significant reduction in the mortality rate. Conversely morbidity rate pattern has a flat trend. Perioperative period is crucial since OHS and CPB are widely accepted as a deliberate hypoxic-ischemic reperfusion damage representing the cost to pay at a time when standard of care monitoring procedures can be silent or unavailable. In this respect, the measurement of neuro-biomarkers (NB), able to detect at early stage perioperative brain damage could be especially useful. In the last decade, among a series of NB, S100B protein has been investigated. After the first promising results, supporting the usefulness of the protein as predictor of short/long term adverse neurological outcome, the protein has been progressively abandoned due to a series of limitations. In the present review we offer an up-dated overview of the main S100B pros and cons in the peri-operative monitoring of adult and pediatric patients.

Diagnostic Mycology: Xtreme Challenges.

Developing any diagnostic assay that receives United States Food and Drug Administration (FDA) approval can be a slow and difficult process. FDA-approved assays for fungal diagnosis are generally few in number and are focused mainly on diagnosing candidiasis, which is caused by several species of Candida, in addition to a limited number of systemic mycotic agents. While all microbial diagnostic assays face challenges before they are FDA approved and reach the market, there are a number of challenges to fungal diagnostic assay development that have been difficult hurdles to overcome. These hurdles include template preparation, fungal morphology, how many fungi should be identified in a single assay (scope), taxonomy and nomenclature, discriminating colonizers from invasive infection, combining identification with antifungal susceptibility, and navigating the administrative hurdles required to integrate an assay into a clinical laboratory. Some of these challenges are easier to overcome than others, but all seem to be particularly difficult for fungal diagnostic assays.

Variant of Rett syndrome and CDKL5 gene: clinical and autonomic description of 10 cases.

UNLABELLED: Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting almost exclusively females. The Hanefeld variant, or early-onset seizure variant, has been associated with mutations in CDKL5 gene. AIMS: In recent years more than 60 patients with mutations in the CDKL5 gene have been described in the literature, but the cardiorespiratory phenotype has not been reported. Our aim is to describe clinical and autonomic features of these girls. METHODS: 10 girls with CDKL5 mutations and a diagnosis of Hanefeld variant have been evaluated on axiological and clinical aspects. In all subjects an evaluation of the autonomic system was performed using the Neuroscope. RESULTS: Common features were gaze avoidance, repetitive head movements and hand stereotypies. The autonomic evaluation disclosed eight cases with the Forceful breather cardiorespiratory phenotype and two cases with the Apneustic breather phenotype. CONCLUSIONS: The clinical picture remains within the RTT spectrum but some symptoms are more pronounced in addition to the very early onset of seizures. The cardiorespiratory phenotype was dominated by Forceful breathers, while Feeble breathers were not found, differently from the general Rett population, suggesting a specific behavioral and cardiorespiratory phenotype of the RTT the Hanefeld variant.

[Atrial fibrillation and thyroid nodules]. / Fibrillazione atriale e noduli tiroidei.

Our previous papers reported an association between atrial fibrillation and supracentimeter thyroid nodules. Recently we noticed that the number of patients admitted to our ward presenting this relationship, was higher than average data relating to whole world's population. In this study we tried to prove the existence of this association in a selected group of inpatients aged between 71 and 80. This to rule-out any age-related confounding factor. We enrolled one hundred inpatients, aged between 71-80. Each patient underwent TSH, FT3, FT4 determination, ECG and thyroid ultrasound examination. 55 males and 45 females: 25 with atrial fibrillation (group A) and 75 without atrial fibrillation (group B). In group A, 80% had supracentimeter thyroid nodules, whereas in group B, only the 6.7% showed supracentimeter thyroid nodules. The rate of supracentimeter thyroid nodules in inpatients without atrial fibrillation (group B) was in line with that found in many studies about whole world's population (4-10%). On the contrary, subjects with atrial fibrillation (group A) showed a rate of supracentimeter thyroid nodules significantly higher (p < 0.001). These findings confirm our previous studies even in more age homogeneous peoples. Moreover, they suggest a link between atrial fibrillation and thyroid nodules. Cytokines and growth factors (IGF-1, EGF, FGF) might act like a connection between nodule goitre and atrial fibrillation.

Using blood data for the differential diagnosis and prognosis of motor neuron diseases: a new dataset for machine learning applications.

Early differential diagnosis of several motor neuron diseases (MNDs) is extremely challenging due to the high number of overlapped symptoms. The routine clinical practice is based on clinical history and examination, usually accompanied by electrophysiological tests. However, although previous studies have demonstrated the involvement of altered metabolic pathways, biomarker-based monitoring tools are still far from being applied. In this study, we aim at characterizing and discriminating patients with involvement of both upper and lower motor neurons (i.e., amyotrophic lateral sclerosis (ALS) patients) from those with selective involvement of the lower motor neuron (LMND), by using blood data exclusively. To this end, in the last ten years, we built a database including 692 blood data and related clinical observations from 55 ALS and LMND patients. Each blood sample was described by 108 analytes. Starting from this outstanding number of features, we performed a characterization of the two groups of patients through statistical and classification analyses of blood data. Specifically, we implemented a support vector machine with recursive feature elimination (SVM-RFE) to automatically diagnose each patient into the ALS or LMND groups and to recognize whether they had a fast or slow disease progression. The classification strategy through the RFE algorithm also allowed us to reveal the most informative subset of blood analytes including novel potential biomarkers of MNDs. Our results show that we successfully devised subject-independent classifiers for the differential diagnosis and prognosis of ALS and LMND with remarkable average accuracy (up to 94%), using blood data exclusively.

Sequence-based identification of filamentous basidiomycetous fungi from clinical specimens: a cautionary note.

The species-level identification of sterile and/or arthroconidium-forming filamentous fungi presumed to be basidiomycetes based upon morphological or physiological features alone is usually not possible due to the limited amount of hyphal differentiation. Therefore, a reliable molecular approach capable of the unambiguous identification of clinical isolates is needed. One hundred sixty-eight presumptive basidiomycetes were screened by sequence analysis of the internal transcribed spacer (ITS) and D1/D2 ribosomal DNA regions in an effort to obtain a species identification. Through the use of this approach, identification of a basidiomycetous fungus to the species level was obtained for 167/168 of the isolates. However, comparison of the BLAST results for each isolate for both regions revealed that only 28.6% (48/168) of the isolates had the same species identification by use of both the ITS and the D1/D2 regions, regardless of the percent identity. At the less stringent genus-only level, the identities for only 48.8% (82/168) of the isolates agreed for both regions. Investigation of the causes for this low level of agreement revealed that 14% of the species lacked an ITS region deposit and 16% lacked a D1/D2 region deposit. Few GenBank deposits were found to be complete for either region, with only 8% of the isolates having a complete ITS region and 10% having a complete D1/D2 region. This study demonstrates that while sequence-based identification is a powerful tool for many fungi, sequence data derived from filamentous basidiomycetes should be interpreted carefully, particularly in the context of missing or incomplete GenBank data, and, whenever possible, should be evaluated in light of compatible morphological features.

Subcutaneous Mycoleptodiscus indicus infection in an immunosuppressed dog.

An 8-year-old dog presented with several dermal excoriations. Lesion cytology revealed pyogranulomatous inflammation with branching, septate hyphae. A mold identified as Mycoleptodiscus indicus by morphology and sequencing was cultured from fine-needle aspirates. This is the first report of a Mycoleptodiscus species as an etiologic agent in a dog.

Cerebral phaeohyphomycosis due to Rhinocladiella mackenziei (formerly Ramichloridium mackenziei): a taxonomic update and review of the literature.

Cerebral phaeohyphomycosis caused by Rhinocladiella mackenziei (formerly Ramichlo-ridium mackenziei) is extremely rare, and geographically limited to the Middle East. The fungus exclusively targets the brain and infections have a grave prognosis. Eighteen cases have been reported in the literature from 1983 to 2004 with almost 100% mortality. Our patient presented in February 2008 with a brain abscess while receiving chemotherapy for carcinoma of the breast. Diagnosis was by craniotomy and aspiration of the brain abscess. Direct microscopy showed dematiaceous fungal hyphae. R. mackenziei was recovered in culture and this identification was confirmed by molecular analysis. Examination of histopathological sections of tissue from the brain biopsy revealed moniliform hyphae characteristic for phaeohyphomycosis. The patient failed to respond to antifungal therapy with amphotericin B and voriconazole or amphotericin B and posaconazole and finally expired 64 days after diagnosis. In vitro antifungal susceptibility testing showed this isolate to be resistant to amphotericin B while susceptible to itraconazole, voriconazole, and posaconazole. Previously published antifungal susceptibility data indicate that although strains show variable susceptibility to amphotericin B, the organism is generally refractory to treatment with this agent. Similar outcomes are seen with the azole agents used alone or in combination with other drugs. Although no specific risk factors have been identified, the majority of cases have occurred in immunocompromised individuals. R. mackenziei is a highly virulent agent of serious cerebral phaeohyphomycosis, and should be considered in the differential diagnosis of central nervous system disease in the Middle East.

Fatal Actinomucor elegans var. kuwaitiensis infection following combat trauma.

We report the first case of invasive mucormycosis secondary to Actinomucor elegans infection. A severely injured soldier with a fatal A. elegans var. kuwaitiensis infection is described. The identification of this fungus was performed by classical and molecular methods, and this report documents the pathogenicity of the recently described variety Actinomucor elegans var. kuwaitiensis.

Cutaneous infection caused by Macrophomina phaseolina in a child with acute myeloid leukemia.

We report a case of Macrophomina phaseolina skin infection in an immunocompromised child with acute myeloid leukemia, which was treated successfully with posaconazole without recurrence after a hematopoietic stem cell transplant. The fungus was identified by DNA sequencing using both the internal transcribed spacer and D1/D2 region of the 28S ribosomal DNA gene.

Cerebral aspergillosis caused by Aspergillus granulosus.

Disseminated disease by Aspergillus granulosus has been reported only once previously in a cardiac transplant recipient. We report a fatal central nervous system infection in a lung transplant recipient. Key features of this species in the section Usti include growth at 37 degrees C and large, randomly spaced aggregates of variably shaped Hülle cells.

Mortality and Morbidity in a Population Exposed to Emission from a Municipal Waste Incinerator. A Retrospective Cohort Study.

In the present research, we evaluated the health effects of exposure to the municipal waste incinerator (MWI) in Pisa, Italy, through a population-based cohort design. The individual exposure pattern in the area was estimated through CALPUFF dispersion models of NOχ (developed by Atmospheric Studies Group Earth Tech, Lowell, Massachusetts), used as pollution proxies of the MWI and the relevant industrial plant, and through land-use regression for NOχ due to traffic pollution. Using Cox regression analysis, hazard ratios (HR) were estimated adjusting for exposure to other sources of pollution, age, and socioeconomic deprivation. An adjusted linear trend of HR (HRt) over the categories of exposure, with the relative 95% CI and p-value, was also calculated. Mortality and hospital discharge were studied as impact outcomes. Mortality analysis on males showed increased trends of mortality due to natural causes (HRt p < 0.05), the tumor of the lymphohematopoietic system (HRt p = 0.01), cardiovascular diseases (HRt p < 0.01); in females, increased trends for acute respiratory diseases (HRt p = 0.04). Morbidity analysis showed a HRt for lymphohematopoietic system tumor in males (HRt p = 0.04). Some of the excesses are in agreement with previous evidence on the health effects of MWIs, although the observation in males but not in females, suggests a cautious interpretation. Confounding due to other sources of exposure cannot be ruled out. The evidence was considered important in the decision-making process of the waste cycle.

[Acute myocardial infarction incidence estimated using a standard algorithm based on electronic health data in different areas of Italy]. / Stima dell'incidenza dell'infarto miocardico acuto basata su dati sanitari correnti mediante un algoritmo comune in differenti aree italiane.

AIM: to define and implement an algorithm, based on current databases, in order to estimate acute myocardial infarction (AMI) incidence in six Italian areas. SETTING: Local Health Units of Firenze and Venezia, and the municipalities of Pisa, Roma, Taranto, and Torino. PARTICIPANTS: residents in the above mentioned six areas in the period 2002-2004, for a total of about 4,447,000 subjects (30th June 2003). METHODS: acute myocardial infarction incident cases were identified through hospitalization databases and causes of death. Hospital discharges (excluding outpatient discharges) with ICD9-CM code 410* as primary discharge diagnosis, or as secondary diagnosis when associated with selected codes suggestive of ischemic symptoms in primary diagnosis, and deaths with the ICD9-CM code 410* as underlying cause were selected. Patients without a previous hospitalization for ICD9-CM codes 410* and 412* during the previous 60 months were considered as incident cases. Crude, age-specific and age-standardized incidence rates (standard: total Italian population at the 2001 census) were calculated. A number of data quality indicators were also evaluated. RESULTS: age-standardized incidence rates show different levels of incidence in the areas included in the study. Both for males and females, higher incidence is observed in Rome and Turin (males: respectively 260.5 and 260.2 cases/100,000; females: 105.6 cases/100,000 in both areas). The lowest incidence is observed in Taranto (males: 219.5 cases/100,000; females: 87.0 cases/100,000). Quality indicators suggest a good comparability of incidence estimates among the studied areas. In particular, in both genders, the differences observed in the incidence rates are consistent with the differences of current AMI mortality rates. CONCLUSIONS: although limitations in data comparability among the studied areas and in the quality of disease coding cannot be completely excluded, results suggest that the algorithm we used provides estimates of AMI incidence rates comparable among the studied areas. Only a validation study with standardized criteria will make it possible to more closely evaluate the diagnostic quality and comparability of AMI cases identified through this algorithm.

[Chronic obstructive pulmonary disease prevalence estimated using a standard algorithm based on electronic health data in various areas of Italy]. / Stima della prevalenza di broncopneumopatia cronico-ostruttiva basata su dati sanitari correnti, mediante l'uso di un algoritmo comune, in differenti aree italiane.

AIM: to estimate the prevalence of chronic obstructive pulmonary disease (COPD) by integrating various administrative health information systems. METHODS: prevalent COPD cases were defined as those reported in the hospital discharge registry (HDR) and cause of mortality registry (CMR) with codes 490*, 491*, 492*, 494* and 496* of the International diseases classification 9th revision. Annual prevalence was estimated in 35+ year-old residents in six Italian areas ofb different sizes, in the period 2002-2004. We included cases observed in the previous four years who were alive at the beginning of each year. RESULTS: in 2003, age-standardized prevalence rates varied from 1.6% in Venice to 5% in Taranto. Prevalence was higher in males and increased with age. The highest rates were observed in central (Rome) and southern (Taranto) cities, especially in the 35-64 age group. HDR contributed 91% of cases. Health-tax exemption registry would increase the prevalence estimate by 0.2% if used as a third data source. CONCLUSIONS: with respect to the National Health Status survey, COPD prevalence is underestimated by 1%-3%; this can partly be due to the selection of severe and exacerbated COPD by the algorithm used. However, age, gender and geographical characteristics of prevalent cases were comparable to national estimates. Including cases observed in previous years (longitudinal estimates) increased the point estimate (yearly) of prevalence two or three times in each area.

[Record-linkage procedures in epidemiology: an Italian multicentre study]. / Procedure di record linkage in epidemiologia: uno studio multicentrico italiano.

OBJECTIVE: To compare record linkage (RL) procedures adopted in several Italian settings and a standard probabilistic RL procedure for matching data from electronic health care databases. DESIGN: Two health care archives are matched: the hospital discharges (HD) archive and the population registry of four Italian areas. Exact deterministic, stepwise deterministic techniques and a standard probabilistic RL procedure are applied to match HD for acute myocardial infarction (AMI) and diabetes mellitus. Sensitivity and specificity for RL procedures are estimated after manual review. Age and gender standardized annual hospitalization rates for AMI and diabetes are computed using different RL procedures and compared. SETTING: Municipalities of Pisa and Roma, and Regions of Puglia and Piemonte. PARTICIPANTS: Residents in the considered areas on 31 December 2003 and corresponding episodes of hospitalization in the same areas during 2004. MAIN OUTCOME MEASURES: Measures of accuracy of RL procedures to match health care administrative databases. RESULTS: Data quality varies among archives and affects the decision rule of the probabilistic procedure. A unique decision rule was therefore adopted by means of choosing a positive predictive value of at least 98% for all the considered areas. The number of matched pairs identified with the probabilistic procedure is on average more then 11% greater than the number identified with the deterministic procedure. Sensitivity of probabilistic RL is similar or greater than that of other procedures. Differences between annual standardized hospitalization rates computed with stepwise deterministic RL and the standard probabilistic RL procedure vary among areas. CONCLUSION: Exact deterministic RL works well when unique identifiers and high quality data are available. The probabilistic procedure here proposed works as well as semi-deterministic RL when the latter implements a quality control of data or a manual review of final results. Otherwise, deterministic or semi-deterministic procedures imply classification errors of unknown size and direction.

[Objectives, tools and methods for an epidemiological use of electronic health archives in various areas of Italy]. / Obiettivi, strumenti e metodi per un utilizzo epidemiologico di archivi sanitari elettronici correnti in diverse aree italiane.

The availability of Electronic Health Archives (EHA) has increased remarkably over the last twenty years. As part of a joint project of the Italian Association of Epidemiology (AIE) and the Italian Association of Medical Statistics and Clinical Epidemiology (SISMEC), a workgroup of experts was set up in 2005 with the aim of comparing various experiences and of standardizing the procedures by which electronic sources can be integrated. In particular, the workgroup's aim was to estimate the frequency of certain major diseases using standard algorithms applied to EHA. This volume is published with the purpose of making available in a common publication the methods and the results obtained. The results from a multicentre study using a standard approach to probabilistic record-linkage procedures are also included in a specific chapter. Eleven Italian centres from five Italian regions with an overall population of 11,932,026 collected and treated more than 21,374,426 records (year 2003) from five electronic information sources: death certificates, hospital discharge records (including outpatient discharges), drug prescriptions, tax- exemptions, and pathology records in order to estimate the frequency of the following diseases: diabetes, ischemic heart diseases, acute myocardial infarction, stroke, asthma, chronic obstructive pulmonary disease, obstructive lung diseases. For each pathology a specific algorithm was developed and used by all centres for the identification of the prevalent/incident cases of the selected diseases. Standardized methods were used to estimate the rates. The results confirm the need for a common standard approach to produce estimates based on EHA, considering the variability of the quality and of the completeness of the archives, and the difficulties of standardizing record-linkage operations in the various centres. The main achievement of this work was the elimination of the variability due to the use of different algorithms to identify cases using EHA.

Correction: How Reliable Are Current Data for Assessing the Actual Prevalence of Chronic Obstructive Pulmonary Disease?

[This corrects the article DOI: 10.1371/journal.pone.0149302.].

How Reliable Are Current Data for Assessing the Actual Prevalence of Chronic Obstructive Pulmonary Disease?

BACKGROUND: Estimating COPD occurrence is perceived by the scientific community as a matter of increasing interest because of the worldwide diffusion of the disease. We aimed to estimate COPD prevalence by using administrative databases from a city in central Italy for 2002-2006, improving both the sensitivity and the reliability of the estimate. METHODS: Multiple sources were used, integrating the hospital discharge register (HDR), clinical charts, spirometry and the cause-specific mortality register (CMR) in a longitudinal algorithm, to reduce underestimation of COPD prevalence. Prevalence was also estimated on the basis of COPD cases confirmed through spirometry, to correct misclassification. Estimating such prevalence relied on using coefficients of validation, derived as the positive predictive value (PPV) for being an actual COPD case from clinical and spirometric data at the Institute of Clinical Physiology of the National Research Council. RESULTS: We found that sensitivity of COPD prevalence increased by 37%. The highest estimate (4.43 per 100 residents) was observed in the 5-year period, using a 3-year longitudinal approach and combined data from three sources. We found that 17% of COPD cases were misclassified. The above estimate of COPD prevalence decreased (3.66 per 100 residents) when coefficients of validation were applied. The PPV was 80% for the HDR, 82% for clinical diagnoses and 91% for the CMR. CONCLUSIONS: Adjusting the COPD prevalence for both underestimation and misclassification of the cases makes administrative data more reliable for epidemiological purposes.

Intra-abdominal pressure monitoring in liver transplant recipients: a prospective study.

OBJECTIVE: No data are available on the incidence and clinical relevance of increased intra-abdominal pressure after orthotopic liver transplantation. This study assessed abdominal hypertension in a population of transplanted patients as this may be an important cofactor in early postoperative complications. DESIGN AND SETTING: Prospective clinical study in an intensive care unit of a national health system teaching hospital PATIENTS AND MEASUREMENTS: Abdominal pressure was measured every 6 h using the urinary bladder method and was considered elevated when it was 25 mmHg or higher. Hemodynamic status was evaluated at the same times. Renal function was assessed on the basis of hourly urinary output by calculating serum creatinine on postoperative days 2 and 4 and the filtration gradient; patient outcomes were also considered. RESULTS: Intra-abdominal hypertension was observed in 32% of cases; the subjects with high abdominal pressure had significantly lower mean artery pressure values but did not differ in terms of central venous pressure or cardiac output. High intra-abdominal pressure was more frequently associated with renal failure, a lower filtration gradient, delayed postsurgical weaning from ventilation, and a worse outcome. CONCLUSIONS: Abdominal hypertension is frequent after liver transplantation and may be associated with a complicated post-operative course.

Postoperative intra-abdominal pressure and renal function after liver transplantation.

HYPOTHESIS: Intra-abdominal hypertension frequently threatens renal function early after orthotopic liver transplantation (OLT). DESIGN: A prospective study of consecutive patients who underwent OLT. SETTING: The intensive care unit of a National Health Service teaching hospital. PATIENTS AND MAIN OUTCOME MEASURES: The intra-abdominal pressure (IAP) of 108 consecutive patients who underwent OLT was postoperatively measured 3 times a day for 72 hours using the urinary bladder technique. Intra-abdominal hypertension was defined as an IAP of 25 mm Hg or higher. RESULTS: Thirty-four patients (31%) had a high IAP. Acute renal failure developed in 17 recipients (16%), 11 (65%) of whom had intra-abdominal hypertension (P<.01), with a mean +/- SD IAP of 27.9 +/- 9.9 mm Hg vs 18.6 +/- 5.2 mm Hg in those without acute renal failure (P<.001). The subjects with a high IAP were more frequently administered loop diuretics to maintain adequate diuresis (P<.001) and had a low mean arterial pressure on the day of surgery (P<.01), despite the fact that they were given more intravenous fluids (P<.01) and did not differ in the need for inotropic drugs. Logistic regression analysis showed that intraoperative transfusions of more than 15 U, respiratory failure, and intra-abdominal hypertension (P<.01) were independent risk factors for renal failure. The length of intensive care unit stay was similar in the patients with a normal and a high IAP, but mortality was higher among the latter (P =.02). CONCLUSIONS: Intra-abdominal hypertension is common after OLT and is significantly associated with renal failure, reduced urinary output, and intensive care unit mortality. It is, therefore, worth monitoring IAP in those undergoing OLT.