Mario Comelli

Rate of progression and prognostic factors in Alzheimer's disease: A prospective study

Objective: To study rate of progression and correlates of cognitive and functional/behavioral deterioration in Alzheimer patients.

Intravenous Versus Combined (Intravenous and Intra-Arterial) Thrombolysis in Acute Ischemic Stroke: A Transcranial Color-Coded Duplex Sonography–Guided Pilot Study

Background and Purpose— Determine feasibility and safety of intravenous (IV) versus combined (IV-IA [intra-arterial]) thrombolysis guided by transcranial color-coded duplex sonography (TCCD). Methods— Thirty-three patients eligible for IV thrombolysis, within 3 hours of onset of symptoms, with occlusion in middle cerebral artery territory (TCCD monitoring, thrombolysis in brain ischemia [TIBI] flow grade [0–3]), underwent IV thrombolysis (tissue plasminogen activator, 0.9 mg/kg). In case of recanalization (modification of TIBI score ≥1) after 30 minutes IV thrombolysis was continued over 1 hour; otherwise, it was discontinued, with subsequent IA thrombolysis. Recanalization was determined by TIBI (TCCD) and angiographically by thrombolysis in myocardial infarction (TIMI) flow grades. Clinical outcome measures were assessed at baseline, 24 hours (NIHSS) and 3 months (modified Rankin Scale). Results— In the IV group, 10/17 patients (59%) with complete or partial recanalization after 30 minutes had a favorable outcome at 3 months (modified Rankin Scale 0 to 2). TIBI flow grades 3 to 5 after 30 minutes of IV thrombolysis predicted a good prognosis compared with TIBI grades 1 to 2 (P<0.05). In the combined IV/IA therapy group (no recanalization after 30 minutes), 9/16 patients (56%) had a favorable outcome at 3 months. One symptomatic intracerebral hemorrhage occurred in each group. Conclusions— Combined IV-IA versus IV thrombolysis guided by TCCD was feasible and safe. Recanalization after 30 minutes of IV thrombolysis led to a favorable outcome in 59% of the patients, provided TIBI flow grades were of 3 to 5. In the absence of early recanalization during IV thrombolysis, there was clinical benefit to proceed to IA therapy for a significative proportion of patients (56%).

Prognostic Validation of the International Classification of Immunoglobulin M Gammopathies: A Survival Advantage for Patients with Immunoglobulin M Monoclonal Gammopathy of Undetermined Significance?

Purpose: To verify the reliability of the new criteria for the diagnosis of IgM gammopathies recently proposed by an international panel of experts (Athens, 2002). Experimental Design: A retrospective series of 698 patients with IgM gammopathy was reviewed paying attention to symptoms, serum IgM concentration, bone marrow infiltration, blood cell count and clinical course. Four clinical entities can be identified: IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), asymptomatic and symptomatic Wandenströms macroglobulinemia (A-WM and S-WM, respectively), and IgM-related disorders, although this last was excluded from the study because of the scarcity of patients due to probable selection biases. The observed mortality was studied related to that expected in the general population of comparable age and sex and over an equivalent period of follow-up (standardized mortality ratio, SMR). Results: IgM-MGUS, A-WM, and S-WM shared many clinical aspects but, with respect to the general population, patients with IgM-MGUS had a slight but definite survival advantage, those with A-WM had a mortality rate equivalent to that of the general population, whereas the SMR of patients with S-WM was 5.4. Within A-WM and S-WM the SMR values did not vary significantly in relation to marrow lymphocyte counts or serum IgM concentrations. Conclusions: Our findings represent a prognostic validation of the applied diagnostic criteria for three of the four identifiable clinical entities and highlight the importance of symptoms over serum IgM concentration and marrow infiltration.

Behavioral effects of omega-3 fatty acid supplementation in young adults with severe autism: an open label study.

BACKGROUND Pilot findings seem to suggest a potential beneficial effect of omega-3 fatty acid (FA) supplementation on behavioral alterations in children with autism. However, data on the potential benefits of omega-3 supplements in young adults with severe autism are lacking. In the present study, we sought to explore this issue in an open label study. METHODS Nineteen young adults with severe autism (CARS >40), aged 18-40 years, received two fish oil capsules per day [0.93 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) plus 5 mg of vitamin E to avoid lipid peroxidation] for 6 weeks. Subjects were assessed with an ad hoc caregiver questionnaire, the Rossago Behavioral Checklist, for the assessment of behavioral anomalies. RESULTS No significant improvements were observed with regard to the severity and frequency of problematic behaviors either during the active treatment period or during the post-treatment 6-week observation period. Moreover, no effect on the number of episodes and severity of behavior aberrations was observed. CONCLUSIONS Our negative findings do not point toward a major effect of omega-3 FA supplementation on behavioral abnormalities in adults with severe autism. Further studies on larger sample sizes are warranted to shed more light on this important issue.

Drug use by the elderly in Italy.

Objectives To evaluate drug consumption in the elderly aged 75 years or more living at home. Design Cross-sectional study. Setting Old-old (i.e., >75 y) people living in central Turin, a city in northern Italy. Participants Thirty-four general practitioners (GPs), with 50 or more old-old people in their patient list, randomly chosen among the GPs working in the Unità Socio-Sanitaria Locale I (Local Health Unit I) of Turin; 261 old-old people (135 men and 126 women) randomly selected from the practice records. Methods Data were collected by the GP through a structured questionnaire during an office visit and by a social worker in a home interview within 14 days of the GP visit GPs were asked to record every diagnosis and drug currently taken by the patient; social workers were trained in the administration of a structured questionnaire exploring sociodemographic variables, drug use (following the medication inventory strategy), disability, cognitive functions, and depressive symptoms. Results Nearly all subjects (95% of the women and 91% of the men) were taking at least 1 drug. The overall number of drugs recorded was 917 (47.1% for men and 52.9% for women), of which 172 (18.8%) were not reported by the GP but were recorded during the social workers visit. The mean number of drugs was 3.2 for men and 3.8 for women, with a statistically significant difference (p = 0.02), while the mean number of diagnoses was 2.3 and 2.6, respectively. The study of correlates of drug consumption showed a strong association with number of diagnoses at univariate analysis (p < 0.0001, with a linear correlation coefficient of 0.64). No multivariate model showed a clear superiority over the simple one containing only the number of diagnoses in predicting the total number of drugs taken. Cardiovascular, nervous system, and alimentary tract drugs were the most frequently used. A total of 107 subjects (41%) were taking at least 1 unreported drug. Conclusions Our study shows high drug consumption among old-old people, with nearly 20% of drugs taken not reported by the GP. These results emphasize the need for an essential therapeutic approach in old-old people, prescribing only drugs of scientifically proven efficacy. Furthermore, the GP must make more effort when collecting a drug history from old-old patients.

Major childhood infectious diseases and other determinants associated with type 1 diabetes: A case-control study

The objective of the study was to evaluate the association between infectious diseases and other events pertaining to childhood medical history and type 1 diabetes. A case-control study was carried out, taking as cases 159 type 1 diabetic patients (0–29 years) recorded from 1988 to 2000 within the population registry of the Pavia province (North Italy). As controls 318 non-diabetic subjects were matched by age and sex. A questionnaire was administered by standardised interviewers. Data were analysed by conditional logistic regression. Viral childhood diseases (OR 4.29; 95%CI 1.57–11.74) and bottle feeding (OR 1.83; 95%CI 1.08–3.09) were directly correlated to type 1 diabetes; an inverse correlation was found for vitamin D administration during lactation (0–14 years) (OR 0.31; 95%CI 0.11–0.86) and for history of scarlet fever in both sexes and age groups (OR 0.19; 95%CI 0.08–0.46). Most associations of the studied variables confirm already known findings. The significant inverse correlation of type 1 diabetes with scarlet fever history is a peculiar finding, the meaning of which is still obscure, although it has been recently described that streptococcal A infections are regulated by HLA class II alleles.

Correlation of Cerebrovascular Symptoms and Microembolic Signals With the Stratified Gray-Scale Median Analysis and Color Mapping of the Carotid Plaque

Background and Purpose— To determine whether a stratified gray-scale median (GSM) analysis of the carotid plaque combined with color mapping correlated better with the presence of neurological symptoms and microembolic signals (MES) than a whole plaque measurement. Methods— A total of 131 patients presenting 167 carotid stenoses between 30% and 99% were analyzed by ultrasound. Emboli detection was performed by transcranial Doppler. For each plaque, the GSM values at depth 0 mm (surface) and at one third (30) and one half (50) of the plaque thickness were compared with the values obtained for the whole plaque. The plaque pixels were mapped into 3 colors: red, yellow and green, depending on their GSM value. Results— Mean GSM values were lower among symptomatic plaques, but a statistically significant difference between values of the whole plaque and those of the surface was obtained only for MES+ stenoses (P<0.01). In a proportional odds logistic regression model based on 4 subgroups with an increasing clinical risk (MES−/symptoms−; MES−/symptoms+; MES+/symptoms−; +; MES+/symptoms+), low mean GSM values and the predominant red color at the surface were independent factors associated with the presence of symptoms or MES (P<0.0005). Furthermore, compared with a whole plaque measurement, analysis of the surface values predicted systematically with a greater sensitivity and specificity (receiver operating characteristic curves) each one of these 4 subgroups. Conclusions— Low mean GSM values and predominance of the red color at the surface correlated with most of the symptomatic or MES+ stenoses. This combined approach should be further investigated in a longitudinal study.

Prediction of lean body mass from multifrequency segmental impedance: influence of adiposity.

Abstract The aim of the study was to determine the influence of adiposity on the relationship between bioelectrical impedance (BIA) measurements of body segments and estimation of body composition by dual-energy X-ray absorptiometry (DXA). Multiple frequencies of whole body and segmental impedances were measured in 68 normal-weight and obese subjects (46 women and 22 men), mean age 37.2±14.8 years (range, 18–69). Total and appendicular lean body mass (LBM) assessed by DXA correlated significantly with total and segmental impedance values adjusted for stature in both obese and normal-weight subjects. Best fitting equations for the prediction of appendicular LBM from segmental impedance measurements were derived for the arm and leg with and without the inclusion of adiposity (the percentage of body fat measured by DXA) in the regression models. Best prediction was obtained at low frequency for the arm and high frequency for the leg. Adiposity appears to significantly influence the prediction of leg LBM by BIA. These preliminary observations need further validation to provide an accurate assessment of appendicular LBM assessment by BIA.

A long diagnostic delay in patients with Hereditary Haemorrhagic Telangiectasia: a questionnaire-based retrospective study

BackgroundThe difficulty in establishing a timely correct diagnosis is a relevant matter of concern for several rare diseases. Many rare-disease-affected patients suffer from considerable diagnostic delay, mainly due to their poor knowledge among healthcare professionals, insufficient disease awareness among patients’ families, and lack of promptly available diagnostic tools. Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal-dominantly inherited vascular dysplasia, affecting 1:5,000-10,000 patients. HHT is characterized by high variability of clinical manifestations, which show remarkable overlapping with several common diseases.AimTo perform a detailed analysis concerning the diagnostic time lag occurring in patients with HHT, defined as the time period spanning from the first clinical manifestation to the attainment of a definite, correct diagnosis.MethodsA questionnaire was administered to the HHT patients previously recruited from 2000 and 2009. Clinical onset, first referral to a physician for disease manifestations, and first correct diagnosis of definite HHT were collected. Eventual misdiagnosis at first referral and serious complications occurring throughout the time elapsing between disease onset and definite diagnosis were also addressed.ResultsIn the 233 respondents, the clinical onset of disease occurred at an age of 14.1 yrs, while the age of first referral and the age of first definite diagnosis of HHT were 29.2 yrs and 40.1 yrs, respectively. Only 88/233 patients received a correct diagnosis at first counseling. Thus, the diagnostic time lag, represented by the time elapsing from disease onset and first definite diagnosis of HHT, proved to be 25.7 yrs. Twenty-two patients suffered from severe complications during this time interval. The diagnostic delay was significantly longer (p < 0.001) in index patients (first patients who attained definite HHT diagnosis in a given family) than in non-index patients (relative of index patients). The diagnostic time lag was also significantly associated with education grade (p < 0.001).ConclusionsOur data report for the first time a systematic inquiry of diagnostic delay in HHT showing that patients receive a definite diagnosis only after nearly three decades from disease onset. Concerted efforts are still to be made to increase awareness of this disease among both families and physicians.

Assessment of lymphocyte subsets and neutrophil leukocyte function in chronic psychiatric patients on long-term drug therapy

1. Lymphocyte subsets and neutrophil function were studied in chronic psychiatric patients on long-term multiple drug therapy, and the correlation with disease and drug treatments was also investigated. 2. Patients showed decreased CD4+ percentage, CD4+/CD8+ ratio, B lymphocyte percentage, increased absolute and percentage NK, and impaired neutrophil chemotaxis, phagocytosis, and oxidative metabolism. Correlations were found between: patient status and lower CD4+ percentage, CD4+/CD8+ ratio, neutrophil chemotaxis, phagocytosis, and oxidative metabolism; schizophrenia and higher absolute and percentage NK, and neutrophil random migration; benzodiazepines and higher CD8+ absolute number and lower NBT reduction frequency; carbamazepine and higher NK percentage, neutrophil chemotaxis, phagocytosis, stimulated O2-production, and lower microbicidal activity. 3. The present study provides direct evidence for the existence of immunologic abnormalities in a population of chronic psychiatric patients on long-term drug therapy. Although a possible role by other factors could not be excluded, such abnormalities are strongly associated with chronic administration of benzodiazepines and carbamazepine. Further investigations are warranted to confirm these findings and disclose the possible mechanism(s) involved.