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.

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.

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.

Repeated insulin-like growth factor 1 treatment in a patient with rett syndrome: a single case study.

Rett syndrome (RTT) is a devastating neurodevelopmental disorder that has no cure. Patients show regression of acquired skills, motor, and speech impairment, cardio-respiratory distress, microcephaly, and stereotyped hand movements. The majority of RTT patients display mutations in the gene that codes for the Methyl-CpG binding protein 2 (MeCP2), which is involved in the development of the central nervous system, especially synaptic and circuit maturation. Thus, agents that promote brain development and synaptic function are good candidates for ameliorating the symptoms of RTT. In particular, insulin-like growth factor 1 (IGF1) and its active peptide (1-3) IGF1 cross the Blood Brain Barrier, and therefore are ideal treatments for RTT Indeed, both (1-3) IGF1 and IGF1 treatment significantly ameliorates RTT symptoms in a mouse model of the disease In a previous study, we established that IGF1 is safe and well tolerated on Rett patients. In this open label clinical case study, we assess the safety and tolerability of IGF1 administration in two cycles of the treatment. Before and after each cycle, we monitored the clinical and blood parameters, autonomic function, and social and cognitive abilities, and we found that IGF1 was well tolerated each time and did not induce any side effect, nor it interfered with the other treatments that the patient was undergoing. We noticed a moderate improvement in the cognitive, social, and autonomic abilities of the patient after each cycle but the benefits were not retained between the two cycles, consistent with the pre-clinical observation that treatments for RTT should be administered through life. We find that repeated IGF1 treatment is safe and well tolerated in Rett patients but observed effects are not retained between cycles. These results have applications to other pathologies considering that IGF1 has been shown to be effective in other disorders of the autism spectrum.

[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.

Stress-inducing factors in ICUs: what liver transplant recipients experience and what caregivers perceive.

The aim of this study was to compare a number of potentially stress-generating factors related to an intensive care unit (ICU) stay from the points of view of patients undergoing liver transplantation or elective major abdominal surgery and their caregivers in order to identify differences and similarities that may help to optimize patient care. The ICU Environmental Stressor Scale questionnaire was administered to 104 liver transplant recipients, 103 major abdominal surgery patients, 35 nurses and 21 physicians. The ICU staff were asked to complete the questionnaire on the basis of their perception of patient stressors. Both patient groups identified Being unable to sleep, Being in pain, Having tubes in nose/mouth, Missing husband/wife, and Seeing family and friends only a few minutes a day as the major stressors; the healthcare providers correctly identified the most stressing factors for the patients, but gave them higher scores. The mean scores were 71.9 +/- 18.7 for the transplant recipients, 66.3 +/- 20.9 for the patients undergoing elective major abdominal surgery, 99.7 +/- 19.2 for the nurses, and 92.7 +/- 16.1 for the physicians (P < 0.001). The qualitative evaluations of potentially stress-inducing ICU situations were substantially the same in the 2 patient groups, but the transplant recipients seemed to feel them more acutely. Although the caregivers identified the most discomforting situations, they overestimated the degree of stress they cause. The staff of each ICU should therefore seek to understand and reduce (even by means of simple interventions) the particular causes of psychophysical stress felt by their patients.

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.

Renal failure and abdominal hypertension after liver transplantation: determination of critical intra-abdominal pressure.

There is growing interest in measuring intra-abdominal pressure (IAP) in postsurgical and critically ill patients because increased pressure can impair various organs and functions. The aim of this study was to evaluate the effect of different IAP levels on the postoperative renal function of subjects undergoing orthotopic liver transplantation. IAP was measured every 8 hours with the urinary bladder pressure method for at least 72 hours after surgery. At the end of the study, the patients were classified on the basis of their IAP values: < or = 18 mm Hg (group A), 19 to 24 mm Hg (group B), > or = 25 mm Hg (group C). The three groups were compared in terms of the incidence of acute renal failure (defined as blood creatinine > 1.5 mg/dL or an increase in the same of > 1.1 mg/dL within 72 hours of surgery), hourly diuresis, blood creatinine, the filtration gradient, hemodynamic variations, and outcome. The incidence of renal failure was higher among the subjects in group C (P < .05 versus group A and < .01 versus group B), who also had higher creatinine levels (P < .01), a greater need for diuretics (P < .01) and a worse outcome (P < .05). Receiver Operator Characteristic curve analysis showed that an abdominal pressure of 25 mm Hg had the best sensitivity/specificity ratio for renal failure. An intra-abdominal pressure of > or = 25 mm Hg is an important risk factor for renal failure in subjects undergoing liver transplant.

Antifungal prophylaxis in liver transplant recipients: a randomized placebo-controlled study.

The aim of this study was to evaluate the efficacy of two antifungal prophylaxis regimens in liver transplant recipients. One hundred and twenty-nine consecutive recipients were randomized to receive sequential treatment with intravenous liposomal amphotericin B + oral itraconazole, intravenous fluconazole + oral itraconazole, or intravenous and oral placebo. Frequency and incidence of mycotic colonization, local and systemic infection of mycotic origin, causes of death, and possible risk factors for mycotic infection were evaluated. The incidence of mycotic colonization was higher in the placebo group ( P<0.01), but there was no significant difference in the incidence of infection between the three groups. Pre-transplant colonization, severity of liver disease, and graft rejection were all risk factors for the development of fungal infection. The routine use of antifungal prophylaxis for all liver transplant recipients does not seem to be justified.