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INTRODUCTION: Critical illness from SARS-CoV-2 infection (COVID-19) is associated with a high burden of pulmonary embolism (PE) and thromboembolic events despite standard thromboprophylaxis. Available guidance is discordant, ranging from standard care to the use of therapeutic anticoagulation for enhanced thromboprophylaxis (ET). Local ET protocols have been empirically determined and are generally intermediate between standard prophylaxis and full anticoagulation. Concerns have been raised in regard to the potential risk of haemorrhage associated with therapeutic anticoagulation. This report describes the prevalence and safety of ET strategies in European Intensive Care Unit (ICUs) and their association with outcomes during the first wave of the COVID pandemic, with particular focus on haemorrhagic complications and ICU mortality. METHODS: Retrospective, observational, multi-centre study including adult critically ill COVID-19 patients. Anonymised data included demographics, clinical characteristics, thromboprophylaxis and/or anticoagulation treatment. Critical haemorrhage was defined as intracranial haemorrhage or bleeding requiring red blood cells transfusion. Survival was collected at ICU discharge. A multivariable mixed effects generalised linear model analysis matched for the propensity for receiving ET was constructed for both ICU mortality and critical haemorrhage. RESULTS: A total of 852 (79% male, age 66 [37-85] years) patients were included from 28 ICUs. Median body mass index and ICU length of stay were 27.7 (25.1-30.7) Kg/m2 and 13 (7-22) days, respectively. Thromboembolic events were reported in 146 patients (17.1%), of those 78 (9.2%) were PE. ICU mortality occurred in 335/852 (39.3%) patients. ET was used in 274 (32.1%) patients, and it was independently associated with significant reduction in ICU mortality (log odds = 0.64 [95% CIs 0.18-1.1; p = 0.0069]) but not an increased risk of critical haemorrhage (log odds = 0.187 [95%CI - 0.591 to - 0.964; p = 0.64]). CONCLUSIONS: In a cohort of critically ill patients with a high prevalence of thromboembolic events, ET was associated with reduced ICU mortality without an increased burden of haemorrhagic complications. This study suggests ET strategies are safe and associated with favourable outcomes. Whilst full anticoagulation has been questioned for prophylaxis in these patients, our results suggest that there may nevertheless be a role for enhanced / intermediate levels of prophylaxis. Clinical trials investigating causal relationship between intermediate thromboprophylaxis and clinical outcomes are urgently needed., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Plasma neurofilament light (NFL) and total Tau (t-Tau) proteins are candidate biomarkers for early stages of Alzheimer’s disease (AD). The impact of biological factors on their plasma concentrations in individuals with subjective memory complaints (SMC) has been poorly explored. We longitudinally investigate the effect of sex, age, APOE ε4 allele, comorbidities, brain amyloid-β (Aβ) burden, and cognitive scores on plasma NFL and t-Tau concentrations in cognitively healthy individuals with SMC, a condition associated with AD development. Methods Three hundred sixteen and 79 individuals, respectively, have baseline and three-time point assessments (at baseline, 1-year, and 3-year follow-up) of the two biomarkers. Plasma biomarkers were measured with an ultrasensitive assay in a mono-center cohort (INSIGHT-preAD study). Results We show an effect of age on plasma NFL, with women having a higher increase of plasma t-Tau concentrations compared to men, over time. The APOE ε4 allele does not affect the biomarker concentrations while plasma vitamin B12 deficiency is associated with higher plasma t-Tau concentrations. Both biomarkers are correlated and increase over time. Baseline NFL is related to the rate of Aβ deposition at 2-year follow-up in the left-posterior cingulate and the inferior parietal gyri. Baseline plasma NFL and the rate of change of plasma t-Tau are inversely associated with cognitive score. Conclusion We find that plasma NFL and t-Tau longitudinal trajectories are affected by age and female sex, respectively, in SMC individuals. Exploring the influence of biological variables on AD biomarkers is crucial for their clinical validation in blood.

AimsType 2 diabetes (T2D) accelerates the decline in glomerular function; however, some individuals do not develop chronic kidney disease despite advanced age and long-lasting T2D. We aimed to phenotype patients with T2D aged 80years or older who presented with a fully preserved kidney function.MethodsFrom an Italian population of 281,217 T2D outpatients, we collected data on demographics, anthropometrics, diabetes duration, HbA1c, fasting plasma glucose, lipids, liver enzymes, estimated glomerular filtration rate (eGFR), albumin excretion rate (AER), chronic complications, and medication use. We primarily compared patients with a fully preserved kidney function (eGFR>90ml/min/1.73m(2) and AER

BACKGROUND: The International Classification of Functioning, Disability and Health (ICF) Generic-30 Set (previously referred to as Rehabilitation Set) is a minimal set of ICF categories for reporting and assessing functioning and disability in clinical populations with different health conditions along the continuum of care. Recently, the Italian Society of Physical and Rehabilitation Medicine (SIMFER) developed an Italian modification of the simple and intuitive descriptions (SID) of these categories. This study was the first one to implement the use of the SID in practice. AIM: The main aims of this study are: 1) to implement the use of the ICF in clinical practice and research among Italian Residents in PRM, and 2) to verify if the SID made the application of ICF Generic 30 Set more user-friendly than the original descriptions; 3) to examine the prevalence of functioning problems of patients accessing Rehabilitation Services to serve as reference for the development of an ICF-based clinical data collection tool. DESIGN: Multicenter cross-sectional study. SETTING: Italian Physical Medicine and Rehabilitation (PRM) outpatient rehabilitation services. POPULATION: Patients referring to Italian PRM outpatient rehabilitation services and Italian Residents in PRM. METHODS: Each School of Specialization involved, randomly, received the ICF Generic-30 Set with the original descriptions or with the SID. Residents collected over a 4-month period (April-July 2016) patients data related to the ICF Generic-30 Set categories. Moreover, the residents self-assessed their difficulty in using the ICF Generic-30 Set with the original descriptions or with the SID, through a Numeric Rating Scale (NRS). RESULTS: Ninety-three residents collected functioning data of 864 patients (mean aged 57.7±19.3) with ICF Generic-30 Set: 304 with the original descriptions and 560 with SID. The difficulty in using the ICF Generic-30 Set with SID was rated as lower than using the original descriptions (NRS 2.8±2.5 vs. 3.5±3.1; P

Familial combined hyperlipoproteinaemia (FCH) is the most common inherited disorder of the lipid metabolism in patients with premature coronary heart disease; it is characterized by a primary variability of the plasma lipid phenotype. Our aim was to estimate its prevalence in the Brisighella Heart Study cohort, a large North-Italian rural population sample monitored from 1972 to 2004. At 2004 survey, 1303 subjects were selected if they were tested in ≥5 four-yearly surveys (mean age 63.74 ± 14.97 years); their first-degree relatives involved in the study were excluded from the FCH prevalence estimation. At each survey, subjects were classified as hypercholesterolaemic, hypertriglyceridaemic or mixed hyperlipidaemic on the basis of their LDL-C (>160 mg/dl) and TG (TG > 200 mg/dl) plasma concentrations. A primary hyperlipoproteinaemia was suspected on the basis of personal and familial case history, BMI and dietary habits in 4% of

The present national survey seeking to identify unmet needs in the management of spasticity with botulinum toxin type A focused on the use of OnabotulinumoxinA, since this is the brand with the widest range of licensed indications in Italy. Physicians from twenty-four Italian neurorehabilitation units compiled a questionnaire about “real-life” post-stroke spasticity management. OnabotulinumtoxinA was reported to be used in the following average doses: upper limb 316.7 ± 79.1 units; lower limb 327.8 ± 152.3; upper and lower limb 543.7 ± 123.7 units. Of the physicians surveyed, 37.5% felt that increasing the frequency of OnabotulinumtoxinA injection would improve its efficacy; 70.8% use electrical stimulation/electromyography guidance (one fourth of injections with no instrumental guidance). Instrumental evaluation was used by 41.7% of the physicians. The participants expressed the view that early identification of post-stroke spasticity would be facilitated by the availability of a post-stroke checklist, and that this should be used by physiotherapists (91.7%), physiatrists (58.3%), family doctors (50%), stroke unit physicians (25%), patients and caregivers (79.2%). According to our findings, the management of poststroke spasticity has several unmet needs that, were they addressed, might improve these patients’ clinical outcomes and quality of life. These needs concern patient follow-up, where a clearly defined pathway is lacking; furthermore, there is a need to use maximum doses per treatment and to ensure early intervention on post-stroke spasticity.

Objective: To assess the results of tricuspid annuloplasty performed with the Edwards MC3 remodeling ring. Methods: From 2005 to 2007, 140 patients with tricuspid regurgitation (TR) secondary to left-sided valve disease (mean age 63.8 +/- 11.6, permanent pacemaker in 7.8%, LVEF 56.4 +/- 10.1%, LVEDD 54.1 +/- 8 mm, SPAP 52.5 +/- 14.4 mmHg) underwent tricuspid annuloplasty using the MC3 ring. Dilatation of the tricuspid annulus was present in all patients. Other concomitant mechanisms of TR (moderate leaflet prolapse, pacemaker wires, leaflets' retraction) were documented in 21 cases (15%). All patients underwent concomitant left-sided valve surgery. Ring size was between 28 and 32 in 84.3% of patients. Results: Hospital mortality was 3.5% and actuarial survival at 3 years 94.8 +/- 2.1%. Mean follow-up of the 135 hospital survivors was 22 +/- 9.5 months (median 23 months). Echocardiography at hospital discharge documented no or mild TR in 119 patients (87%), moderate TR (2+/4+) in 15 (11%) and moderate-to-severe (3+/4+) in 1 patient (0.7%). At echocardiographic follow-up moderate TR was present in 14 patients (10.3%) and moderate-to-severe TR in 2 (1.4%). At 3 years freedom from TR >= 2+ was 88.1 +/- 2.78% and freedom from TR >= 3+ was 94.3 +/- 4.89. Predictors of TR >= 2+ at hospital discharge and at follow-up were preoperative LVEF (OR:0.8; p = 0.001 at discharge; HR:0.9; p = 0.003 at follow-up) and the presence of other mechanisms of TR besides annular dilatation (OR:10.8; p = 0.007 at discharge; HR:6.1; p = 0.003 at follow-up). Conclusion: Tricuspid annuloplasty with the MC3 ring provides satisfactory early results which remain stable at mid-term follow-up. The presence of other mechanisms besides annular dilatation leads to residual valve insufficiency after ring annuloplasty alone. doi: 10.1111/j.1540-8191.2012.01443.x (J Card Surg 2012;27:288-294)

Background The aim of this study is to assess the clinical value of a recently introduced original protocol for full three dimensional analysis of ankle rotations in patients with equinovarus foot. Methods A preliminary study merging the Total3Dgait protocol and the conventional Vicon® Plug-in-Gait marker-sets on five patients with foot deformity was performed to compare the output exactly over the same gait cycles. In the second study, 15 patients with equinus varus foot were assessed retrospectively by means of the Total3Dgait protocol before and after surgery. Data on ankle kinematics were compared to those of a control group. The Functional Ambulation Categories scale and other goals such as orthosis/aids removal, decrease in foot pain, healing of calluses and sores were considered as measures of clinical outcome. Findings The Total3Dgait protocol provides additional joint motion, in the coronal and transverse planes. Kinematics in the three anatomical planes improved significantly although no changes in time-distance parameters were evident. Improvement in clinical outcome measures was also achieved. Interpretation The new protocol provides valuable additional data in measuring full three dimensional kinematics of the foot during gait. Whereas the speed of walking was unchanged after surgery for most of patients, the kinematic changes in the three anatomical planes, as measured by the new protocol, were the only measures able to demonstrate motion changes induced by surgery at the foot and to explain subject-specific gains as improvement in stability during walking, relief of pain, calluses and sores, and removal or modification of foot orthosis and aids.

Objectives: To describe results from a novel percutaneous technique designed to minimize the risk of hemorrhage in the event of a major complication during transcatheter aortic valve implantation. Background: Vascular access management is a major challenge in transfemoral TAVI due to the large introducer sheathes required. Methods: Fifty-two pts underwent TAVI between November 2007 and March 2009. Of these, 37 received an Edwards-Sapien Valve (23 mm valve: 17/37; 26 mm valve: 20/37) whilst 15 patients received a CoreValve (26 mm valve: 6/15; 29 mm valve: 9/15). Using a crossover technique, the opposing femoral artery was cannulated with a 7Fr long sheath. This allowed contralateral passage of a balloon and inflation in the proximal iliac. The sheath was then removed and Prostar sutures tied in a dry field. Balloon optimization of the puncture site was performed as required. Results: In three subjects, elective surgical repair was undertaken due to excessive femoral arterial calcification. In the remaining 49, the crossover technique was employed and closed with two Prostar devices (Edwards-Sapien) or one (CoreValve). There were serious “on-table” complications in seven patients, six due to the large introducer sheathes used in the TAVI procedure—iliac avulsion, two iliac dissections, iliac perforation, common femoral perforation and scrotal hematoma. All were repaired safely by combined surgical and endovascular techniques, using the crossover technique to ensure patient stability. All made a good recovery and were independently ambulant at discharge. Conclusion: Using crossover balloon inflation as an adjunct to Prostar closure may be helpful for managing TAVI vascular access sites. © 2009 Wiley-Liss, Inc.

Epidemiological data from the Framingham and other prospective studies suggests an inverse correlation between the plasma concentration of HDL-cholesterol (HDL-C) and the incidence of cardiovascular disease. The relationship between HDL-C and its vascular-protective effects is particularly due to the heterogeneity of these particles and their important role in reverse cholesterol transport. It is well-known that many different factors are involved in metabolic regulation of HDL and can affect their plasma concentration. Apolipoprotein A-I, the principal apolipoprotein of HDL, is synthesized and secreted in the intestine and liver, where several enzymatic processes contribute to the biogenesis and the catabolism of HDLs. In this review we report and analyze the main clinical, genetic and environmental determinants of plasma HDL-C concentration; moreover we underline how different laboratory methods of HDL-C dosage can influence the correct assessment of these plasma values. We present a comparison of HDL-C...

Conference scene of the satellite meeting of the 14th International Congress on Atherosclerosis, on "Physical activity, exercise and cardiovascular health"

Objectives Various investigators believe that alcoholic chronic pancreatitis is the result of recurrent episodes of acute necrotic pancreatitis. The aim of this work is to study pancreatic histology in early stages of the disease to search for evidence of these acute episodes. Study Of about 650 patients with alcoholic pancreatitis seen during the 30-year period from 1972 to 2002, 45 underwent surgery for this disease, all within 2 years of clinical onset. Of these 45, tissue samples adequate for study were obtained from 42, and this was the study material. Tissue samples were prepared for histologic examination by standard procedures. Results Areas of pancreatic necrosis were seen in tissue samples of only three (7%) of the 42 patients, and in all three cases chronic lesions were also present. No evidence of localized scarring that could be attributed to prior episodes of focal necrotic pancreatitis was found. A typical feature was the patchy distribution of the lesions in largely normal pancreatic tissue. The main lesions observed were perilobular and intralobular fibrosis, dilation of acini and ducts, and protein plugs in dilated ducts surrounded by periductal fibrosis. Conclusions This study shows that, in the early stages of alcoholic chronic pancreatitis, signs of acute necrotic pancreatitis are very infrequent and, when present, they are associated with chronic lesions. These findings suggest that alcoholic pancreatitis begins as a chronic disease.

OBJECTIVES Idiopathic pancreatic hyperenzymemia is a new syndrome that is characterized by a chronic increase of serum pancreatic enzymes in the absence of pancreatic disease. The aim of this study was to assess whether mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene may have a role in the etiology of this hyperenzymemia. METHODS Seventy subjects with idiopathic pancreatic hyperenzymemia, 44 men and 26 women (mean age, 48 years; range, 8-74 years), were studied. Thirteen of these 70 subjects had the familial form of the syndrome. The mutation analysis of the CFTR gene was carried out using diagnostic commercial kits for the simultaneous detection of 29 mutations and Tn polymorphism. RESULTS Among the 70 subjects studied, 7 (10.0%) had CFTR gene mutations. None of these 7 subjects had the familial form of pancreatic hyperenzymemia. These mutations were DeltaF 508 in 1 subject, 2789 + 5 G > A in another subject, and T5 allele in the remaining 5. All these mutations were heterozygous, with the exception of 1 T5 allele that was homozygous in 1 subject. CONCLUSIONS The frequencies of the mutations of the CFTR gene found in these subjects are similar to the carrier frequencies in the general Italian population. This finding does not support a role for CFTR gene mutations in the etiology of idiopathic pancreatic hyperenzymemia.

BACKGROUND: Knee dislocation is a severe but relatively uncommon injury caused by violent trauma that can result in long-term complications, such as arthrofibrosis, stiffness, instability, and pain. Perhaps owing in part to its rarity, treatment of this injury is controversial. We therefore describe a treatment approach for these complex cases involving a novel dynamic knee external fixator. DESCRIPTION OF TECHNIQUE: We performed open PCL reconstruction when possible and/or repair of other associated lesions. At the end of the surgical procedure, the surgeon applied an external fixator that reproduced normal knee kinematics, allowing early motion exercises and reducing the risk of joint stiffness while protecting the bony and soft tissue structures involved in the repair during the first healing phase. PATIENTS AND METHODS: We retrospectively reviewed eight patients treated with this approach, four of whom had the PCL reconstructed and four of whom had only associated injuries reconstructed. We evaluated all patients with clinical scores (subjective International Knee Documentation Committee form, Lysholm score, and Tegner level), physical examination (objective International Knee Documentation Committee form), and KT-1000™ arthrometer for AP laxity. Minimum followup was 10 months (mean, 26 months; range, 10-45 months). RESULTS: One patient had manipulation under anesthesia. The median Lysholm score was 76, Tegner level was 4, and subjective International Knee Documentation Committee was 73. All patients recovered to their preinjury work activity, except one unemployed patient. Stability was normal or nearly normal in five patients; the mean side-to-side difference in AP displacement with manual maximum force was 2.9 mm. CONCLUSIONS: This approach with an external fixator allowed staged reconstruction and early motion and provided reasonable stability, ROM, and activity level at followup in patients with complex injuries. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Picelli A, Bonetti P, Fontana C, Barausse M, Dambruoso F, Gajofatto F, Girardi P, Manca M, Gimigliano R, Smania N. Is spastic muscle echo intensity related to the response to botulinum toxin type A in patients with stroke? A cohort study. Objective To investigate the relationship between gastrocnemius muscle echo intensity and response to botulinum toxin type A (BoNT-A) in patients with spastic equinus foot resulting from stroke. Design Cohort study. Setting University hospital. Participants Adult patients (N=56) with spastic equinus foot resulting from stroke scheduled to receive BoNT-A injection into the gastrocnemius muscle. Interventions All patients were injected with BoNT-A (abobotulinumtoxinA) into the gastrocnemius muscle with an ultrasonography-guided, multisite injection technique. The toxin dose was 250U for the gastrocnemius medialis and 250U for the gastrocnemius lateralis (dilution 500U/2mL) in each patient. All patients were evaluated before and 4 weeks after BoNT-A injection. Main Outcome Measures Spastic gastrocnemius muscle echo intensity visually graded with the Heckmatt scale. Clinical assessment of the spastic gastrocnemius with the Modified Ashworth Scale, Tardieu Scale, and ankle passive range of motion. Results Postintervention testing at 4 weeks showed overall significant improvements in the clinical assessment of the spastic gastrocnemius muscle. No significant change was observed in the echo muscle intensity of the spastic gastrocnemius after BoNT-A injection. Post hoc comparisons showed that all clinical outcomes were significantly better in those patients with echo muscle intensity of the spastic gastrocnemius graded II on the Heckmatt scale than those with grades III ( P P Conclusions These findings support the hypothesis that patients with higher spastic muscle echo intensity have a reduced response to BoNT-A.

This paper investigates the ability of a single wireless inertial sensing device stuck on the lower trunk to provide spatial-temporal parameters during level walking. The 3-axial acceleration signals were filtered and the timing of the main gait events identified. Twenty-two healthy subjects were analyzed with this system for validation, and the estimated parameters were compared with those obtained with state-of-the-art gait analysis, i.e. stereophotogrammetry and dynamometry. For each side, from four to six gait cycles were measured with the device, of which two were validated by gait analysis. The new acquisition system is easy to use and does not interfere with regular walking. No statistically significant differences were found between the acceleration-based measurements and the corresponding ones from gait analysis for most of the spatial-temporal parameters, i.e. stride length, stride duration, cadence and speed, etc.; significant differences were found for the gait cycle phases, i.e. single and double support duration, etc. The system therefore shows promise also for a future routine clinical use.

The reliability of kinematic measurements has a top priority in gait analysis. The aim of the present work was to assess the inter-trial, inter-session and inter-examiner variability of an anatomical-based protocol by an established method. The gait of two young adult volunteers was analyzed by four examiners with different degrees of experience in three sessions 1 week apart. The data of five trials of level walking were collected and the rotations in the three anatomical planes of the pelvis, hip, knee and ankle were calculated. Themean value over the gait cycle of the standard deviation of these rotations wascalculated for each of the 24 groups of five trials (inter-trial), the eight groups of five trials multiplied by three sessions (intersession), and the two groups of five trials multiplied by three sessions multiplied by four examiners (interexaminer). For each rotation, the inter-examiner variability was larger than the inter-session, and the latter larger than the inter-trial. The present ratio between inter-examiner and inter-trial variability wasfound to be smaller than that of the conventional protocol for each of the gait variables. 2010 Elsevier B.V. All rights reserved.

Most widespread clinical gait analysis protocols for lower limb kinematics provide information about the ankle motion only in the sagittal plane. Behavior of the foot in the coronal plane during gait is usually determined just through the measure of the foot angle of progression. In the clinical practice most of the patients, particularly with upper motor disease, present a complex deformity of the foot in the three anatomical planes, most frequently in equinus, varus, supinated foot. Adequate kinematic analysis requires full consideration of the 3D ankle-foot complex position and motion on the basis of appropriate biomechanical conventions. The aim of the present work is to test the efficacy of current kinematic protocols for gait analysis in the measurement of 3D motion in stroke patients with foot deformities before and after surgery.

In the setting of a six-month, open-label clinical trial, 141 consecutively enrolled, hypertensive, overweight patients were randomized to the oral ingestion of psyllium powder or guar gum 3.5 gr t.i.d., to be taken 20 min before the main two meals, or to standard diet. Both fibers improved significantly BMI, FPG, FPI, HOMA Index, HbA1c, LDL-C, and ApoB. Psyllium supplementation only exerted a significant improvement in plasma TG concentration, in SBP and DBP. In our study, six-month supplementation with psyllium fiber, but not with guar fiber nor standard diet, appears to significantly reduce both SBP and DBP in hypertensive overweight subjects.

Recent evidences suggest that modulation of vascular structure by matrix metalloproteinases (MMPs) could be a main determinant of acute cardiovascular events in high-risk subjects. The authors consecutively selected 46 subjects affected by familial combined hyperlipidemia (FCH), 44 by metabolic syndrome (MS), 44 by FCH and MS, and 40 healthy subjects. All these subjects were firstly diagnosed and not treated with lipid-lowering, antihypertensive, or antidiabetic drugs. A 12-h fasting blood sample was obtained from each patient, and plasma levels of MMP-2 and MMP-9 were measured together with their tissue inhibitors and a full set of laboratory cardiovascular disease markers. MMP-2 plasma levels were not significantly different among the considered groups. MMP-9, tissue inhibitor of MMP (TIMP)-1, and TIMP-2 are significantly higher in FCH (p < .001) and MS (p < .001) patients than in healthy controls, and they are also higher in MS patients than in FCH ones (p < .001). TIMP-1 (p < .001) and TIMP-2 (p < .001), but not MMP-9, are also significantly higher in subjects with MS associated to FCH than in patients with MS alone. No specific correlation among MMPs, TIMPs, and the other studied parameters has been observed in the whole sample and in the four above-defined subgroups. MMP-9, TIMP-1, and TIMP-2 plasma levels could be significant determinant and/or diagnostic markers of MS but not of FCH. However, the superposition of MS on FCH further increases the plasma level of these parameters. The prognostic value of this observation has to be evaluated.

Alcoholic pancreatitis is an old disease that continues to present controversial issues. One of the most hotly debated issues is whether alcoholic pancreatitis is a chronic disease from the beginning or if instead it becomes chronic after repeated episodes of acute pancreatitis. Histologic studies, including very large series of patients with alcoholic pancreatitis, have clearly shown that this disease is chronic from the beginning and that, if acute necrotic pancreatitis occurs, it is associated with chronic lesions. The possibility that acute alcoholic pancreatitis can occur in the absence of chronic lesions cannot be excluded, but, if this occurs, it is rare. In addition to alcohol, genetic factors certainly play a determining role. Until now many genetic studies have been made on chronic pancreatitis; the first dealt with hereditary pancreatitis. In this disease it has been shown that mutations of the cationic trypsinogen gene and of SPINK1 are implicated in its pathogenesis. Concerning alcoholic pancreatitis, several studies have been made, but the results so far are disappointing.

Mitochondrial impairment has been implicated in the pathogenesis of the amyotrophic lateral sclerosis (ALS). Furthermore, mitochondrial-specific polymorphisms were previously related to other neurodegenerative diseases, such as Parkinson, Friedreich and Alzheimer disease. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of sporadic ALS (sALS), we have genotyped predefined European mtDNA haplogroups in 222 Italian patients with sALS and 151 matched controls. Individuals classified as haplogroup I demonstrated a significant decrease in risk of ALS versus individuals carrying the most common haplogroup, H (odds ratio 0.08, 95% confidence interval 0.04-0.4, p < 0.01). Further stratification of the dataset by sex, age and site of onset of disease and survival failed to reach significance for association. Our study provides evidence of the contribution of mitochondrial variation to the risk of ALS development in Caucasians. Further it may help elucidate the mechanism of the mitochondrial dysfunction detectable in ALS, and may be of relevance in development of strategies for the treatment of this disease.

Objectives: Whether acute alcoholic pancreatitis occurs in a normal pancreas or in a pancreas that has already been altered by chronic pancreatitis is unclear. Our objective is to clarify the relation between acute and chronic alcoholic pancreatitis by histologic study of the pancreas in a group of patients having a first attack of acute alcoholic pancreatitis. Methods: From January 1989 to December 1999, 138 patients with acute pancreatitis, of whom 28 had alcoholic pancreatitis, were seen by us; in 21 of the latter 28 patients, it was the first attack. Of these 21, 6 underwent surgery for acute necrotic pancreatitis. In all 6 patients, adequate pancreatic biopsies were obtained during surgery. Tissue samples were prepared for histologic examination according to standard procedures. Results: In all 6 patients, both acute necrotic and chronic lesions were found. The chronic lesions had characteristics of chronic calcifying pancreatitis and consisted of perilobular and intralobular fibrosis, loss of exocrine parenchyma, dilated interlobular ducts, and protein plugs within dilated ducts. Conclusions: This study suggests that acute alcoholic pancreatitis develops in a pancreas already affected by chronic pancreatitis. The hypothesis that in alcoholics chronic pancreatitis derives from acute pancreatitis is not supported by the present data.