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to explore clinical and epidemiological characteristics associated with an imaging feature of COVID-19 pneumonia at disease onset, in order to identify factors that may be evaluable by general practitioners at patient's home, and which may lead to identify a more severe disease, needing hospitalization.this is a retrospective/prospective observational hospital cohort.the study population includes all patients consecutively admitted to the emergency department of Città della salute e della scienza University Hospital from 01.03 to 31.05.2020 with a confirmed diagnosis of SARS-CoV-2 infection.patients were classified in two groups according to the findings of X-ray imaging, lung ultrasound and chest computer tomography, as pneumonia or not pneumonia patients.in multivariable analysis, factors most strongly associated with emergency department admission with pneumonia were age, oxygen saturation90% (adj OR 4.16 ;95%CI 1.44-12.07), respiratory rate24 breaths/min (adj OR 6.50; 95%CI 2.36-17.87), fever ≥38° (adj OR 3.05; 95%CI 1.53-6.08) and the presence of gastroenteric symptoms (vomiting and diarrhea). A delay (7 days) between the appearance of the initial lung symptoms (cough and dyspnea) and the admission to the emergency department was also related to a higher probability of receiving a positive imaging report (OR 4.99; 95%CI 2,02-12,34).in order to reorganize the management of COVID-19 patients in Italy, in view of the risk of a second wave of epidemic or of local outbreaks, it would be desirable to relocate the triage, and possibly the patient's care, from hospital to home. In this scenario it is important to identify all symptoms and signs associated with COVID-19 pneumonia that would facilitate the decision-making process of GPs leading to patients hospitalization.

IntroductionThe ERAS protocol (Enhanced Recovery After Surgery) is a multimodal pathway aimed to reduce surgical stress and to allow a rapid postoperative recovery. Application of the ERAS protocol to colorectal cancer surgery has been limited to a minority of hospitals in Italy. To promote the systematic adoption of ERAS in the entire regional hospital network in Piemonte an Audit and Feedback approach (A&F) has been adopted together with a cluster randomised trial to estimate the true impact of the protocol on a large, unselected population.MethodsA multicentre stepped wedge cluster randomised trial is designed for comparison between standard perioperative management and the management according to the ERAS protocol. The primary outcome is the length of hospital stay (LOS). Secondary outcomes are: incidence of postoperative complications, time to patients’ recovery, control of pain and patients’ satisfaction. With an A&F approach the adherence to the ERAS items is monitored through a dedicated area in the study web site. The study includes 28 surgical centres, stratified by activity volume and randomly divided into four groups. Each group is randomly assigned to a different activation period of the ERAS protocol. There are four activation periods, one every 3 months. However, the planned calendar and the total duration of the study have been extended by 6 months due to the COVID-19 pandemic.The expected sample size of about 2200 patients has a high statistical power (98%) to detect a reduction of LOS of 1 day and to estimate clinically meaningful changes in the other endpoints.Ethics and disseminationThe study protocol has been approved by the Ethical Committee of the coordinating centre and by all participating centres. Study results will be timely circulated within the hospital network and published in peer-reviewed journals.Trial registration numberNCT04037787.

Hospital discharge can potentially represent an issue. Therefore, it is important to early identify patients at higher risk. A valid tool in this field is the Blaylock Risk Assessment Screening Score (BRASS).The study aims to elaborate a simplified score system, throughout the contribution of healthcare professionals considering the single items of the original score.The study included a qualitative analysis, conducted in order to draft the synthetic tool. Alongside, a statistical analysis was carried out. The findings of these two works were compared and joined in the realization of the proposed evaluation tool.The synthetic tool, developed by the working team, is composed by 20 items. The qualitative analysis agrees with the statistical approach. Moreover, the qualitative analysis consented to redefine some items, especially considering social support, and to include some additional information e.g. clinical problems.The analysis considered only General Medicine wards, all located in the same Hospital. Therefore, generalisation to other settings or patients should be further tested.The synthetic tool, realized during the study, aims to improve the individuation of at-risk inpatients. The agreement between statistical and qualitative analysis can be considered a point of strength of our work. Our analysis consented to include some new items, improving overall organization. In conclusion, the working group aims to conduct further study in order to individuate the more appropriate cut-off of the new scoring method.

Context: Tracheotomy is used to replace endotracheal intubation in patients requiring prolonged ventilation; however, there is considerable variability in the time considered optimal for performing tracheotomy. This is of clinical importance because timing is a key criterion for performing a tracheotomy and patients who receive one require a large amount of health care resources. Objective: To determine the effectiveness of early tracheotomy (after 6-8 days of laryngeal intubation) compared with late tracheotomy (after 13-15 days of laryngeal intubation) in reducing the incidence of pneumonia and increasing the number of ventilator-free and intensive care unit (ICU)-free days. Design, Setting, and Patients: Randomized controlled trial performed in 12 Italian ICUs from June 2004 to June 2008 of 600 adult patients enrolled without lung infection, who had been ventilated for 24 hours, had a Simplified Acute Physiology Score II between 35 and 65, and had a sequential organ failure assessment score of 5 or greater. Intervention: Patients who had worsening of respiratory conditions, unchanged or worse sequential organ failure assessment score, and no pneumonia 48 hours after inclusion were randomized to early tracheotomy (n=209; 145 received tracheotomy) or late tracheotomy (n=210; 119 received tracheotomy). Main Outcome Measures: The primary endpoint was incidence of ventilator-associated pneumonia; secondary endpoints during the 28 days immediately following randomization were number of ventilator-free days, number of ICU-free days, and number of patients in each group who were still alive. Results: Ventilator-associated pneumonia was observed in 30 patients in the early tracheotomy group (14%; 95% confidence interval [CI], 10%-19%) and in 44 patients in the late tracheotomy group (21%; 95% CI, 15%-26%) (P=.07). During the 28 days immediately following randomization, the hazard ratio of developing ventilator-associated pneumonia was 0.66 (95% CI, 0.42-1.04), remaining connected to the ventilator was 0.70 (95% CI, 0.56-0.87), remaining in the ICU was 0.73 (95% CI, 0.55-0.97), and dying was 0.80 (95% CI, 0.56-1.15). Conclusion: Among mechanically ventilated adult ICU patients, early tracheotomy compared with late tracheotomy did not result in statistically significant improvement in incidence of ventilator-associated pneumonia. Trial Registration: clinicaltrials.gov Identifier: NCT00262431. ©2010 American Medical Association. All rights reserved.

Background We investigated the addition of rituximab to dose-dense and high-dose chemotherapy with autologous stem cell transplantation in patients with untreated poor-prognosis diffuse large B-cell lymphoma.Design and Methods Ninety-four young patients (age, 18–60) with stage III–IV diffuse large B-cell lymphoma at intermediate/high or high risk according to the age-adjusted International Prognostic Index were enrolled into a phase II trial. The treatment was as follows: four courses of bi-weekly rituximab-cyclophosphamide-epirubicin-vincristine-prednisone (R-MegaCEOP14), two courses of rituximab-mitoxantrone-cytarabine-dexamethasone (R-MAD) and carmustine-etoposide-cytarabine-melphalan (BEAM) with autologous stem cell transplantation.Results The complete response and toxic death rates were 82% and 5%, respectively. Failure-free survival and overall survival rates at 4 years were 73% and 80%, respectively. The outcomes of these patients were retrospectively compared to those of 41 patients with similar characteristics enrolled into a previous phase II trial of high-dose chemotherapy without rituximab. This historical group was treated with eight weekly infusions of methotrexate-doxorubicin-cyclophosphamide-vincristine-prednisone-bleomycin (MACOP-B), two courses of MAD and BEAM with autologous stem cell transplantation. The 4-year failure-free survival rates for the rituximab and historical groups were 73% versus 44%, respectively (p=0.001); the 4-year overall survival rates were 80% and 54%, respectively (p=0.002). A Cox’s multivariable model was applied to adjust the effect of treatment for unbalanced or important prognostic factors: failure and death risks were significantly reduced in the rituximab group compared to the historical group, with an adjusted hazard ratio of 0.44 (p=0.01) for failure-free survival and 0.46 (p=0.02) for overall survival.Conclusions These results suggest that the addition of rituximab to high-dose chemotherapy is effective and safe in diffuse large B-cell lymphoma with a poor-prognosis and such regimens need to be compared to dose-dense chemoimmunotherapy without autologous stem cell transplantation in randomized trials.

The initial analysis of the oral combination melphalan, prednisone, and thalidomide (MPT) in newly diagnosed patients with myeloma showed significantly higher response rate and longer progression-free survival (PFS) than did the standard melphalan and prednisone (MP) combination and suggested a survival advantage. In this updated analysis, efficacy and safety end points were updated. Patients were randomly assigned to receive oral MPT or MP alone. Updated analysis was by intention to treat and included PFS, overall survival (OS), and survival after progression. After a median follow-up of 38.1 months, the median PFS was 21.8 months for MPT and 14.5 months for MP (P = .004). The median OS was 45.0 months for MPT and 47.6 months for MP (P = .79). In different patient subgroups, MPT improved PFS irrespective of age, serum concentrations of β2-microglobulin, or high International Staging System. Thalidomide or bortezomib administration as salvage regimens significantly improved survival after progression in the MP group (P = .002) but not in the MPT group (P = .34). These data confirm activity of MPT for PFS but failed to show any survival advantage. New agents in the management of relapsed disease could explain this finding. The study is registered at www.clinicaltrials.gov as #NCT00232934.

Summary Background Since 1960, oral melphalan and prednisone (MP) has been regarded as the standard of care in elderly multiple myeloma patients. This multicentre randomised trial compared oral MP plus thalidomide (MPT) with MP alone in patients aged 60–85 years. Methods Patients with newly diagnosed multiple myeloma were randomly assigned to receive oral MP for six 4-week cycles plus thalidomide (n=129; 100 mg per day continuously until any sign of relapse or progressive disease) or MP alone (n=126). Analysis was intention-to-treat. This study is registered at ClinicalTrial.gov, number NCT00232934. Results Patients treated with thalidomide had higher response rates and longer event-free survival (primary endpoints) than patients who were not. Combined complete or partial response rates were 76·0% for MPT and 47·6% for MP alone (absolute difference 28·3%, 95% CI 16·5–39·1), and the near-complete or complete response rates were 27·9% and 7·2%, respectively. 2-year event-free survival rates were 54% for MPT and 27% for MP (hazard ratio [HR] for MPT 0·51, 95% CI 0·35–0·75, p=0·0006). 3-year survival rates were 80% for MPT and 64% for MP (HR for MPT 0·68, 95% CI 0·38–1·22, p=0·19). Rates of grade 3 or 4 adverse events were 48% in MPT patients and 25% in MP patients (p=0·0002). Introduction of enoxaparin prophylaxis reduced rate of thromboembolism from 20% to 3% (p=0·005). Conclusion Oral MPT is an effective first-line treatment for elderly patients with multiple myeloma. Anticoagulant prophylaxis reduces frequency of thrombosis. Longer follow-up is needed to assess effect on overall survival.

Blood stream infections (BSIs) remain one of the major causes of morbidity and mortality for patients receiving an allogeneic hematopoietic stem cell transplantation (HSCT). In the present study, we evaluated the incidence and characteristics of BSI within 1 year after allogeneic HSCT in 269 consecutive adult patients who received antibacterial prophylaxis with levofloxacin. Cumulative incidence of BSI was 12% (95% confidence interval, 8-16%). Bacteria were responsible for 30 out of the 32 BSI, while fungi were responsible for 2 episodes of BSI. The median onset of BSI was day 8 (range 1-328 days) post transplant, and 66% of BSI occurred before neutrophil recovery. Gram-positive organisms accounted for 60% (n=18) of bacteremia, and gram-negative isolates for 40% (n=12) of the cases. Coagulase-negative staphylococci were the most commonly isolated gram-positive pathogens (53% of the cases), while Escherichia coli was the most commonly isolated gram-negative bacteria (58% of the cases). Candida albicans and Candida guillermondii were isolated from patients with candidemia. Resistance to fluoroquinolones (FQ) was common with 13% of gram-positive isolates being susceptible to FQ, while 50% of the gram-negative rods were susceptible to FQ. Crude mortality and mortality attributable to BSI were both 3% (1 of 32). In conclusion, our data suggest that despite the emergence of antibiotic resistance, FQ prophylaxis may be considered an appealing approach in allogeneic HSCT recipients and is also worth evaluating in randomized studies.

Several data suggest that neuroendocrine (NE) differentiation in prostate cancer is implicated in the development of resistance to androgen-deprivation therapy (ADT). This study was undertaken to assess the prognostic role of tissue chromogranin A (CgA) expression in patients addressed to ADT as opposed to those who did not.Four hundred fourteen newly diagnosed prostate cancer patients, consecutively recruited in a single institution, entered the study. Two hundred fourteen patients received ADT early after diagnosis, 200 did not. Median follow-up was 85 months. CgA expression was evaluated immunohistochemically in prostate cancer needle biopsies.In multivariate analysis after adjusting for Gleason score, serum PSA, disease stage and local treatments, tissue CgA expression in overall cases was significantly associated with a shorter survival (P = 0.009) but failed to be associated with PSA progression (P = 0.10). Dividing patients according to whether they received immediate ADT or not, tissue CgA was associated with a shorter time to PSA progression in ADT-treated patients (hazard ratios (HR) 1.96, 95% confidence interval (CI): 1.37-2.81, P = 0.0001), but failed to be associated in those who did not (HR 0.87, 95% CI: 0.58-1.30, P = 0.49), interaction test P = 0.007. Conversely the survival effect of tissue CgA was not modified by ADT (interaction test, P = 0.41).Tissue CgA expression, evaluated in prostate cancer needle biopsies at diagnosis, is an independent prognostic factor of survival in prostate cancer patients. The negative influence of NE differentiation on time to progression confined in ADT-treated patients suggests a role of NE differentiation in predicting endocrine resistance that deserves validation.

Purpose In the area of anticancer drugs, the legitimate search for effective interventions can be jeopardized by the strong pressure for accelerated approval, which may hinder the full assessment of their benefit-risk profile. We aimed to produce drug-specific recommendations using an explicit approach that separates the judgments on quality of evidence from the judgment about strength of recommendations. Materials and Methods We used the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system to develop recommendations for the use of specific anticancer drugs/regimens; 12 clinical questions relevant to adjuvant treatment of breast (three), colorectal (four) and lung (five) cancer have been assessed by multidisciplinary panels supported by a group of methodologists. Results For nine of 12 questions, recommendations were produced (one strong and six weak in favor and one weak and one strong against the index treatment); for the remaining three questions no specific course of action could be recommended. The perceived benefits to risk balance of the treatment was the most important and statistically significant (P < .01) predictor of panels’ recommendations and of their strength, whereas panelists’ personal (age, sex) and professional (specialty) characteristics were not statistically associated. Conclusion Because the GRADE system sets out an explicit process going from evaluation of the quality of evidence and benefit-risk profile to the judgment of the strength of recommendations, in this experience, it proved very useful to combine methodologic rigor with the interdisciplinary participation that is important in the definition of evidence based clinical policies.

To determine whether the guidelines (LGR) prepared in Piedmont for the treatment of colorectal and breast cancer reached the targetphysician population and how they were been perceived by physicians.We invited all Piedmont hospital units that had treated at least 5 cases of colon-rectal or breast cancer in 2002 to participate to the survey. Physicians had to fill a short mail questionnaire. The questionnaire had three sections: distribution and implementation, quality of the instrument, utility and applicability.Replies were 65% (53/82) and 73% (105/143) respectively for the for colon rectal cancer guidelines (LGR-CR) and for breast cancer guidelines (LGR-M)). Among responders, 6% and 9% units ignored the existence of the LGR-CR and LGR-M respectively. More than 50% responders participated in the LGR presentation meetings and/or working groups for the local implementation of LGR. Overall the units judged the LGR quality positively. The LGR utility was judged positively for LGR-CR but opinions were heterogeneous for LGR-M. The LGR-M were judged unable to improve the doctor-patient relationship--or the continuity of care.The physicians who replied to the questionnaires had received the LGRs and are familiar with them. Furthermore they had a positive attitude towards the instrument. The LGR-CR seems to be better accepted than LGR-M, for which some resistance was found among gynaecologists and radiotherapists. However, very few responders described how they formally implemented the instrument in their clinical practice. Absence of LGR promotion activities (such as working groups) and low patient volume were relevant factors in limiting local implementation.

Purpose Lenalidomide has shown significant antimyeloma activity in clinical studies. Oral melphalan, prednisone, and thalidomide have been regarded as the standard of care in elderly multiple myeloma patients. We assessed dosing, efficacy, and safety of melphalan, prednisone, and lenalidomide (MPR) in newly diagnosed elderly myeloma patients. Patients and Methods Oral melphalan was administered in doses ranging from 0.18 to 0.25 mg/kg on days 1 to 4, prednisone at a 2-mg/kg dose on days 1 to 4, and lenalidomide at doses ranging from 5 to 10 mg on days 1 to 21, every 28 days for nine cycles, followed by maintenance therapy with lenalidomide alone. Aspirin was given as a prophylaxis for thrombosis. Results Fifty-four patients were enrolled and evaluated after completing the assigned treatment schedule. The maximum tolerated dose was defined as 0.18 mg/kg melphalan and 10 mg lenalidomide. With these doses, 81% of patients achieved at least a partial response, 47.6% achieved a very good partial response, and 23.8% achieved a complete immunofixation-negative response. In all patients, 1-year event-free and overall survival rates were 92% and 100%, respectively. At the maximum tolerated dose, grade 3 adverse events included neutropenia (38.1%), thrombocytopenia (14.2%), febrile neutropenia (9.5%), vasculitis (9.5%), and thromboembolism (4.8%); grade 4 adverse events were neutropenia (14.2%) and thrombocytopenia (9.5%). Conclusion Oral MPR therapy is a promising first-line treatment for elderly myeloma patients. Hematologic adverse events were frequent but manageable. A low incidence of nonhematologic adverse events was noted. Aspirin appears to provide adequate antithrombosis prophylaxis.

Outpatient activity recording system has a potential role in clinical practice evaluation. Nevertheless, up to now, its utilisation has been limited by the paucity of its clinical data. This study describes a procedure for identifying the oncological diagnosis in patients receiving radiotherapy at an ambulatory service in the Piedmont Region. The procedure is based on the record linkage between discharge records (SDO) and outpatients records (PA), in order to obtain clinical information from the diagnosis related to possible admissions of the patients.The study analyzed radiotherapy outpatients records in 2003 related to Piedmont residents and all discharge records in years 2000-2004. The quality of the procedure has been assessed by using the information on the real oncological diagnosis as reported in the outpatients medical records of a random sample of patients.The record linkage with SDO allows to define an oncological diagnosis for 82% (95% CI 78.5-84.8) of the patients. Agreement between defined diagnosis and the real one is 85.7% (CI 95% 82.2-88.6). The validity of the procedure is affected by the patients' cancer site. The distribution by cancer site of the patients treated with radiotherapy in Piedmont Region obtained with the record linkage procedure is homogeneous to the real distribution of the random sample used for control.Overall, the record linkage between SDO and radiotherapy PA shows a good performance in defining the oncological diagnosis of the patients receiving radiotherapy at an ambulatory setting. This method allows to increase interest and utility of PA records.

The increase in the prevalence of asthma and allergies observed during the last decades has been largely investigated, but the reasons for such trend are still unclear. The distribution of factors traditionally considered responsible of the allergic disorders (such as pollen or moulds), do not explain the geographical differences observed internationally in the prevalence of asthma and allergies. The conduction of new studies aimed at monitoring the trend in asthma and allergies, and in the risk factors associated with these disorders, such as the SIDRIA study (Italian Studies on Respiratory Disorders in Children and the Environment), will shed new light on this phenomenon.

One of the main objectives of SIDRIA-2 study was to evaluate the possible changes in the occurrence of social characteristics and risk factors for asthma and allergies in childhood, comparing the data obtained in 2002 to those collected in 1994-1995. A positive change in socio-economic characteristics of the childrens' and adolescents' families was generally observed. The levels of exposure to outdoor (traffic) and indoor (passive smoking) pollutants are still high, although a decreasing trend in parents' smoking habits is evident.

To compare hospital mortality in a cardiac surgery unit with external data and to assess changes in time (patients undergoing surgery in two different periods).Data on risk factors for hospital mortality were collected from clinical records (retrospectively for the first period and prospectively for the second) for all patients undergoing open heart surgery at the Heart Surgery Unit of the University of Turin (Italy) during 1991 and 1995 (n = 1794) and 1999 (n = 892). Comparisons of in-hospital mortality, expressed as Standardized Mortality Ratios (SMR), were adjusted for risk factors defined according to EuroSCORE (European System for Cardiac Operative Risk Evaluation).In the first and second period, complete information on all the 17 EuroSCORE items was available for 58.3% and 89.6% patients respectively. After exclusion of patients with one or more missing data, observed and expected numbers of death were found to be very similar, with SMRs ranging between 0.82 (isolated bypass in the second period) and 1.06 ("other" surgery in the first period). Mortality was higher among patients with missing data, but at least in 1999 the latter had a limited impact on the overall estimates. Compared to the first period, mortality was reduced during 1999 (from 5.9% to 5.4%), in particular for isolated bypass (from 4.4% to 3.4%).In the unit under investigation, hospital mortality following heart surgery was similar to that predicted from EuroSCORE and seemed to be lower in 1999 than in 1991-95, particularly for isolated bypass. Incompleteness of data on individual risk factors may have been a source of bias, especially when data were collected retrospectively.

Background: Variations in the prevalence of respiratory symptoms according to geo-climatic factors could provide important clues to the knowledge of the aetiology of asthma. Methods: Geo-climatic variations in the prevalence of current asthma, allergic rhinitis and chronic cough, and phlegm were assessed on a random sample of 18 873 subjects (response rate = 72.7%) from different climatic regions of Italy. An ecological analysis, supported by robust statistical methods, was employed to investigate potential trends. Results: The prevalence of all symptoms was significantly heterogeneous throughout the peninsula. Only asthma-like symptoms showed a north–south trend: the prevalence increased at a decreasing latitude [odds ratio (OR) varies from 0.92 to 0.96, P

Essential Thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by a long median survival, even though serious complications such as acute hemorrhagic or thrombotic events are not infrequent. Very few information are available about risk factors for ET because of lack of epidemiological studies focused on this topic.We conducted a case-control study in order to analyze the possible association between ET and some occupational and environmental risk factors. A total of 93 patients enrolled in two hospitals in Turin (Italy) and 280 subjects randomly selected from the general population as controls, were included in the analysis.We found an association between ET and selected occupations. OR estimates suggest a significant association between ET cooks/waiters (OR 4.96, CI 1.59-16.9) and clerks (OR 2.63, CI 1.53-4.51) and a non significant association between ET and hairdressers (OR 5.10, CI 0.82-31.4), nurses (OR 3.75, CI 0.80-19.4), farmers (OR 1.74, CI 0.84-3.56), electricians (OR 1.42, CI 0.48-3.78), and photographers (OR infinity). Data did not suggest any strong association between environmental risk factors and ET.Selected occupations seem to be associated to ET. The association of ET with occupations as hairdressers, farmers and electricians could be attributable to known risk factors for other hematolymphopoietic malignancies such as hair dye, pesticides and magnetic fields. The association with other occupations is more difficult to explain, but all the results we presented are consistent with data from previous studies on onco-hematological diseases.

This study was undertaken to evaluate the usefulness of hospital discharge data for monitoring the impact of a regional practice guideline on treatment of colorectal cancer. The aims of the study were: i) estimating process and outcome indicators; ii) exploring the relationship between patient and hospital characteristics and these indicators. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for all risk factors analysed. All 3,614 patients undergoing potentially curative resection for rectal cancer in 75 hospitals in Piedmont (Italy) between 1997 and 2000 were included. Occurrences of abdominoperineal resections (APR), postoperative complications, reinterventions and hospital mortality were 16.2%, 11.0%, 5.5% and 4.4%, respectively. APR was performed more frequently in patients with distant metastases or urgently admitted and by hospitals with a lower volume of cases (25 per year) compared to hospital with more than 50 cases per year (OR = 1.50, CI = 1.16-1.94). The strongest predictors for mortality and complications were: older age, distant metastases and urgency of admission. Incidence of complications and of reinterventions was also increased among males and in patients with lesions of the lower rectum. The rate of complications showed an increasing trend during the period, from 8.5% to 14.5% likely reflecting improvement in coding during time. Low hospital workload was associated to a reduced risk of complications and reinterventions, but there was evidence of underreporting of secondary diagnoses and procedures in smaller hospitals. Outcome indicator based on secondary diagnoses and procedures are of limited value in monitoring improvement of care since they reflect also differences in coding during time and among providers.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines underline that the presence of chronic cough and sputum production before airflow obstruction offers a unique opportunity to identify subjects at risk of chronic obstructive pulmonary disease for an early intervention. Current epidemiological data on these subjects are scant. Between 1998-2000, the authors evaluated the prevalence and characteristics of these symptoms by a multicentre cross-sectional survey of Italian people aged between 20-44 yrs from the general population (Italian Study on Asthma in Young Adults (ISAYA)). Besides the questions on asthma, more than 18,000 subjects answered the question: "Have you had cough and phlegm on most days for as much as 3 months per year and for at least two successive years?" The adjusted prevalence of subjects with chronic cough and phlegm was 11.9%, being 11.8% in males and 12.0% in females. From these subjects approximately 20% reported coexisting asthma and approximately 30%, predominately females, were nonsmokers. The survey showed that sex (female), smoking and low socioeconomic status were significantly and independently associated with chronic cough and phlegm, current smoking playing the major role. The prevalence of subjects with chronic cough and phlegm is startlingly high among young adults. Further follow-up studies are needed to establish how many of them will go on to develop chronic obstructive pulmonary disease.

The prevalence of asthma and allergic rhinitis has increased worldwide during the 1970s and 1980s.This study was aimed at evaluating whether the increasing trend in prevalence persisted during the 1990s in the young adult Italian population.In 1998 to 2000 a screening questionnaire was sent by mail to a general population sample aged 20 to 44 years; nonresponders were contacted again first by mail and then by phone, achieving a final response rate of 78.1% (6876 of 8800). Prevalence estimates, adjusted to correct for nonresponse bias, were compared with those recorded in Italy in 1991 to 1993 during the European Community Respiratory Health Survey, when response rate had been slightly higher (87.6%). Temporal variations in symptom prevalence were analyzed by a logistic regression model, controlling for sex, age, site of residence (urban vs suburban areas), season of response, response rate, and type of contact (mail vs phone).The prevalence of asthma attacks did not vary significantly from 1991 to 1993 (3.6%) to 1998 to 2000 (3.2%) (P =.188). The prevalence of asthma-like symptoms (wheezing, chest tightness, shortness of breath) tended to decrease in the age classes of 32.5 to 45 years, while increasing in the youngest age class (20 to 26 years). A clear-cut increase from 15.4% to 18.3% was observed for the prevalence of allergic rhinitis (P.001), whereas the proportion of people under antiasthmatic treatment increased in suburban areas but not in urban areas (interaction time-site of residence, P.001).Asthma prevalence has not increased during the last decade in Italy. The persistence of an increasing trend in allergic rhinitis prevalence deserves attention.

The knowledge of the natural history of asthma from birth to adulthood could provide important clues for its cause and for the understanding of epidemiologic findings.This study is aimed at assessing the incidence and remission of asthma from birth to the age of 44 years by using data from 18,873 subjects involved in a large, nationally representative, cross-sectional study carried out in Italy from 1998 through 2000.The onset of asthma was defined as the age at the first attack, and remission was considered present when a subject was neither under treatment nor had experienced an asthma attack in the last 24 months. Person-years and survival techniques were used for the analysis.The average annual incidence rate for the 1953 to 2000 period was 2.56/1000 persons per year. Incidence peaked in boys less than 10 years of age (4.38/1000 persons per year) and in women 30 years of age or older (3.1/1000 persons per year) and showed a generational increase (incident rate ratio = 2.63 and 95% CI = 2.20-3.12 for 1974-1979 vs 1953-1958 birth cohort). The overall remission rate was 45.8% (41.6% in women and 49.5% in men, P.001). Asthmatic patients in remission had an earlier age at onset (7.8 vs 15.9 years, P.001) and a shorter duration of the disease (5.6 vs 16.1 years, P.001) than patients with current asthma. The probability of remission was strongly (P.001) and inversely related to the age at onset (62.8% and 15.0% in the10- andor =20-years age-at-onset groups, respectively).With respect to its natural history, asthma presents 2 different forms: early-onset asthma, which occurs early in childhood, affects mainly boys, and has a good prognosis, and late-onset asthma, which generally occurs during or after puberty, mainly affects women, and has a poor prognosis. The minority of patients with early-onset asthma who do not remit represents more than 35% of patients with current asthma in the general young adult population.

The validity of discharge diagnosis of amyotrophic lateral sclerosis (ALS) and of the main procedures performed during hospitalization was assessed using as gold standard the data from the Piemonte and Valle d'Aosta Register for ALS (PARALS), a collaborative population-based registry aimed at determining prospectively the incidence and the factors related to ALS outcome. All patients discharged with ICD code 335.2 (primary and secondary diagnoses) in the period 1995-1996 in Piemonte, Italy, were considered. Out of the 1,049 cases identified, 433 remained after excluding patients not resident in Piemonte and repeated admissions. Of these, 258 had a correct diagnosis of ALS (168 incident and 90 prevalent cases) after a review of clinical records. The sensitivity of discharge diagnoses was 78.9%, and the positive predictive value was 38.8%. The sensitivity for main procedures (percutaneous endoscopic gastrostomy, noninvasive ventilation, and tracheostomy) ranged between 76 and 100%. ICD codes allowed to identify 22 cases that had not been ascertained with other sources. In conclusion, hospital discharge records appear to poorly reflect the incidence of ALS, and can be used only after clinical verification of the diagnosis.

Epidemiological and clinical information on respiratory and allergic disorders in adolescents has been collected from the adolescents themselves or from their parents, but little is known about the differences between these two sources of information. This study compared the responses to 10 identically worded questions from the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire on asthma, rhinitis and eczema between written self- and parent-completed questionnaires in a large sample of 21,068 adolescent Italians aged 13-14 yrs. The effects of sex, latitude of residence, urbanization, socioeconomic status, previous diagnosis of asthma, family history of allergic diseases and adolescent's smoking habits on the prevalence estimates obtained with the two questionnaires were analysed using multiple logistic regression. Prevalence of self-reported symptoms was significantly higher in self-reported for all questions except for lifetime eczema, which was higher in parental report. Agreement between the two sources of information was poor, although it was slightly better for questions relative to clinical diagnosis of asthma, hay fever or eczema than for related symptoms, and for respiratory with respect to cutaneous disorders. When compared with self-reported, parent-reported was consistently higher in males and was more affected by socioeconomic level and by a diagnosis of asthma or family history of allergic diseases, whereas self-reported was more sensitive to the effect of the adolescent's smoking habits. It is concluded that, in adolescents, parent- and self-reported respiratory and allergic symptoms differ significantly and are differently affected by several constitutional and environmental factors. Obtaining direct information from adolescents may be essential for a correct evaluation of respiratory symptoms.

Summary Rationale and objectives Response to mailed epidemiological surveys has decreased in recent decades. Since subjects with respiratory symptoms are usually early responders to surveys performed in Southern Europe, this trend could bias prevalence estimates. The present study aimed at evaluating the impact of non-response bias on prevalence estimates of respiratory symptoms and smoking habits. Methods In 9 centres, participating in the Italian Study on Asthma in Young Adults (ISAYA), random samples of people aged 20–45 years were administered a mailed questionnaire between 1998 and 2000. Non-responders were contacted again first by mail and then by phone. Cumulative response percentage was 30.5%, 52.4% and 72.7% (18,873/25,969), respectively, after the 1st, 2nd and 3rd contact. Results The prevalence of self-reported current asthma, asthma-like symptoms, and chronic cough/phlegm was more than halved from the first contact (5.6%, 17.8%, 14.6% respectively) to the third contact (2.7%, 6.4%, 6.9%). This pattern was less pronounced when considering allergic rhinitis and past asthma, whose prevalence decreased, respectively, from 21.5% to 15.6% and from 3.5% to 2.6%. At the same time the proportion of current smokers increased from 29.2% to 38%, while the proportion of ex-smokers decreased from 16.5% to 10.1%. In a multinomial logistic model current asthma, asthma-like symptoms, chronic cough/phlegm and smoking habits, and to a lower extent past asthma and allergic rhinitis, were significant predictors of late response. Conclusions In Italy when response percentage is low, the prevalence of current asthma, chronic cough/phlegm and ex-smokers is overestimated, while the proportion of current smokers is underestimated.

Though the term 'nephritis' first appeared in the 19th century, this word did not bear the same meaning as it does today; indeed, for many years it was used to indicate 'renal diseases' (in the sense of Bright's disease) in a larger sense. This review summarizes the long gestation of the concept of 'glomerulonephritis' from the prehistory of medicine up to the beginning of the second half of the 20th century with emphasis on Italy and, in particular, on Torino, which was the capital of the Kingdom of Italy from 1861 to 1865. To the best of our kowledge, this is the first study reporting an epidemiology survey of Bright's disease in Italy from 1880 up to 1960. Towards the end of the 19th century, Bright's disease accounted for 26 deaths/year/10(5) population (in comparison with more than 200 from tuberculosis) in Italy, roughly paralleling that reported in the USA. At the beginning of the 20th century, Bright's disease was the seventh cause of death (almost 1% of total deaths) in Italy. Furthermore, in Italy, as elsewhere, autopsy studies showed a higher percentage of deaths attributed to Bright's disease (5-7%) in comparison with those obtained from vital statistics. In 1960, just before the beginning of renal replacement therapy, Bright's disease accounted for 15.7 deaths/year/10(5) population (= 1.46% of all deaths), roughly paralleling that reported in the United Kingdom (13.8/10(5) population = 1.25% of deaths). Probably, it was difficult to recognize the real incidence of chronic renal diseases leading to death in the 1960s, and vital statistics were able to furnish only approximate estimates. However, noteworthy is the fact that these values were very close to those estimated as being the annual need for renal replacement therapy (10-20 cases/year/10(5) population).

Key Points The prognosis of patients with advanced HL who achieved CMR after both 2 and 6 ABVD cycles is excellent without consolidation RT.An additional benefit of consolidation RT of sites >5 cm is likely to be small and could not be proved for this small sample size., Visual Abstract, The role of consolidation radiotherapy (RT) for bulky lesions is controversial in patients with advanced-stage Hodgkin lymphoma who achieve complete metabolic response (CMR) after doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD)–based chemotherapy. We present the final results of the Fondazione Italiana Linfomi HD0801 trial, which investigated the potential benefit of RT in that setting. In this phase 3 randomized study, patients with a bulky lesion at baseline (a mass with largest diameter ≥5 cm) who have CMR after 2 and 6 ABVD cycles were randomly assigned 1:1 to RT vs observation (OBS) with a primary endpoint of event-free survival (EFS) at 2 years. The sample size was calculated estimating an EFS improvement for RT of 20% (from 60% to 80%). The secondary end point was progression-free survival (PFS). One hundred sixteen patients met the inclusion criteria and were randomly assigned to RT or OBS. Intention-to-treat (ITT) analysis showed a 2-year EFS of 87.8% vs 85.8% for RT vs OBS (hazard ratio [HR], 1.5; 95% confidence interval [CI], 0.6-3.5; P = .34). At 2 years, ITT-PFS was 91.3% vs 85.8% (HR, 1.2; 95% CI, 0.5-3; P = .7). Patients in CMR randomly assigned to OBS had a good outcome, and the primary end point of a 20% benefit in EFS for RT was not met. However, the sample size was underpowered to detect a benefit of 10% or less, keeping open the question of a potential, more limited role of RT in this setting. This trial was registered at www.clinicaltrials.gov as #NCT00784537.

Summary Background & aims The refeeding syndrome (RFS) has been recognized as a potentially life-threatening metabolic complication of re-nutrition, but the definition widely varies and, its incidence is unknown. The aim of this systematic review and meta-analyses was to estimate the incidence of RFS in adults by considering the definition used by the authors as well as the recent criteria proposed by the American Society of Parenteral and Enteral Nutrition (ASPEN) consensus. Furthermore, the incidence of refeeding hypophosphatemia (RH) was also assessed. Methods Four databases were systematically searched until September 2020 for retrieving trials and observational studies. The incidences of RFS and RH were expressed as percentage and reported with 95% confidence intervals (CI). Results Thirty-five observational studies were included in the analysis. The risk of bias was serious in 16 studies and moderate in the remaining 19. The incidence of RFS varied from 0% to 62% across the studies. No substantial change in the originally reported incidence of RFS was found by applying the ASPEN criteria. Similarly, the incidence of RH ranged between 7% and 62%. In the subgroup analyses, inpatients from Intensive Care Units (ICUs) and those initially fed with >20 kcal/kg/day seemed to have a higher incidence of both RFS (pooled incidence = 44%; 95% CI 36%–52%) and RH (pooled incidence = 27%; 95% CI 21%–34%). However, due to the high heterogeneity of data, summary incidence measures are meaningless. Conclusion The incidence rate of both RFS and RH greatly varied according to the definition used and the population analyzed, being higher in ICU inpatients and in those with increased initial caloric supply. Therefore, a universally accepted definition for RFS, taking different clinical contexts and groups of patients into account, is still needed to better characterize the syndrome and its approach.

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BACKGROUND: the Covid-19 pandemic has provoked a huge of clinical and epidemiological research initiatives, especially in the most involved countries. However, this very large effort was characterized by several methodological weaknesses, both in the field of discovering effective treatments (with too many small and uncontrolled trials) and in the field of identifying preventable risks and prognostic factors (with too few large, representative and well-designed cohorts orcase-control studies). OBJECTIVES: in response to the fragmented and uncoordinatedresearch production on Covid-19, the italian Association of Epidemiology (AIE) stimulated the formation of a working group (WG) with the aims of identifying the most important gaps in knowledge and to propose a structured research agenda of clinical and epidemiological studies considered at high priority on Covid-19, including recommendations on the preferable methodology. METHODS: the WG was composed by 25 subjects, mainly epidemiologists, statisticians, and other experts in specific fields, who have voluntarily agreed to the proposal. The agreement on a list of main research questions and on the structure of the specific documents to be produced were defined through few meetings and cycles of document exchanges. RESULTS: twelve main research questions on Covid-19 were identified, covering aetiology, prognosis,interventions, follow-up and impact on general and specific populations (children, pregnant women). For each of them, a two-page form was developed, structured in: background, main topics, methods (with recommendations on preferred study design and warnings for bias prevention) and an essential bibliography. CONCLUSIONS: this research agenda represents an initial contribution to direct clinical and epidemiological research efforts on high priority topics with a focus on methodological aspects. Further development and refinements of this agenda by Public Health Authorities are encouraged.

Strong prognostic markers able to stratify lung adenocarcinoma (ADC) patients are lacking. We evaluated whether a six-immunohistochemical markers panel (TTF1, SP-A, Napsin A, MUC5AC, CDX2 and CK5), defining the putative neoplastic “cell of origin,” allows to identify prognostic subgroups among lung ADC. We screened a large cohort of ADC specimens (2003–2013) from Torino Institutional Repository identifying: (i) marker positivity by immunohistochemistry, (ii) main morphological appearance by light microscopy, (iii) presence of “hotspot” mutations of candidate genes by Sequenom technology. To evaluate possible predictors of survival and time to recurrence, uni- and multivariable-adjusted comparisons were performed. We identified 4 different subgroups: “alveolar,” “bronchiolar,” “mixed” and “null type." Alveolar-differentiated ADC were more common in young (P =.065), female (P =.083) patients, frequently harboring EGFR-mutated (P =.003) tumors with acinar pattern (P

A retrospective study was performed on 27 patients with hepatitis C (HCV)-related mixed cryoglobulinemia (purpura, arthralgia, hepatitis, glomerulonephritis, peripheral neuropathy) to assess peripheral nerve involvement during follow-up of up to 8 years. All patients had the same degree of organ/system involvement initially and were clinically evaluated at least annually. All 27 patients received steroids; 15 also received recombinant interferon-alpha 2b (rIFN-alpha 2b). At first examination, neurological signs and electrodiagnostic findings consistent with peripheral neuropathy were found in 20 (74%) and in 24 (88.8%) patients, respectively. Neurological evaluation and electrodiagnostic data at 3 and 8 years revealed worsening of neuropathy, whereas the other manifestations of mixed cryoglobulinemia (MC) were stable. At the last examination, clinical and electrodiagnostic signs of neuropathy were found in 25 patients (92.5%), occurring in 1 of 3 patients with normal initial findings, and worsened in 8. A more severe neuropathy was observed in 3 (25%) of the patients treated with prednisone alone and in 6 (40%) of the patients additionally treated with rIFN-alpha 2b. Our data confirm that in patients with HCV-related MC, peripheral nerve involvement is frequent, is progressive, and does not seem to benefit by addition of rIFN-alpha 2b to steroid treatment.

High-dose therapy is an effective standard treatment for multiple myeloma patients. Evidence that intermediate-dose therapy improves survival is limited. At diagnosis, about 70% of patients are older than 65. Intermediate-dose regimen is very well tolerated in older patients. In a multicenter study, 194 patients were randomized to receive at diagnosis either conventional chemotherapy (6 courses of oral melphalan and prednisone [MP]) or intermediate-dose therapy (2 courses of melphalan at 100 mg/m(2) [MEL100]) with stem cell support. Response rate was higher after MEL100. Near-complete remission (nCR) was 6% after MP and 25% after MEL100 (P = .0002). At 3 years, MEL100 increased event-free survival (EFS) from 16% to 37% and overall survival (OS) from 62% to 77% (P < .001). Similar results were observed in patients aged 65 to 70: nCR was 8% after MP and 25% after MEL100 (P = .05); at 3 years, MEL100 improved EFS from 18% to 31% (P = .01) and OS from 58% to 73% (P = .01). Patients aged 65 to 70 had a median OS of 37.2 months (MP) versus 58 months (MEL100). Intermediate-dose melphalan improves response rate, EFS, and OS in myeloma patients, specifically in those aged 65 to 70. It constitutes a more effective first-line regimen than standard treatment for elderly patients.

BACKGROUND: This open-label, randomized, phase 3 study compared melphalan at a dose of 200 mg per square meter of body-surface area plus autologous stem-cell transplantation with melphalan-prednisone-lenalidomide (MPR) and compared lenalidomide maintenance therapy with no maintenance therapy in patients with newly diagnosed multiple myeloma. METHODS: We randomly assigned 273 patients 65 years of age or younger to high-dose melphalan plus stem-cell transplantation or MPR consolidation therapy after induction, and 251 patients to lenalidomide maintenance therapy or no maintenance therapy. The primary end point was progression-free survival. RESULTS: The median follow-up period was 51.2 months. Both progression-free and overall survival were significantly longer with high-dose melphalan plus stem-cell transplantation than with MPR (median progression-free survival, 43.0 months vs. 22.4 months; hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.32 to 0.61; P

This multicenter, open-label phase 2 trial determined the safety and efficacy of carfilzomib, a novel and irreversible proteasome inhibitor, in combination with cyclophosphamide and dexamethasone (CCyd) in patients with newly diagnosed multiple myeloma (NDMM) ≥65 years of age or who were ineligible for autologous stem cell transplantation. Patients (N 5 58) received CCyd for up to 9 28-day cycles, followed by maintenance with carfilzomib until progression or intolerance. After a median of 9 CCyd induction cycles (range 1-9), 95% of patients achieved at least a partial response, 71% achieved at least a very good partial response, 49% achieved at least a near complete response, and 20% achieved stringent complete response. After a median follow-up of 18 months, the 2-year progression-free survival and overall survival rates were 76% and 87%, respectively. The most frequent grade 3 to 5 toxicities were neutropenia (20%), anemia (11%), and cardiopulmonary adverse events (7%). Peripheral neuropathy was limited to grades 1 and 2 (9%). Fourteen percent of patients discontinued treatment because of adverse events, and 21% of patients required carfilzomib dose reductions. In summary, results showed high complete response rates and a good safety profile. This trial was registered at clinicaltrials.gov as #NCT01346787. © 2014 by The American Society of Hematology.

Purpose To evaluate the efficacy of rituximab maintenance in 60- to 75-year-old patients with advanced follicular lymphoma responding to brief first-line chemoimmunotherapy followed by rituximab consolidation. Patients and Methods A total of 234 treatment-naive 60- to 75-year-old patients began chemoimmunotherapy with four monthly courses of rituximab, fludarabine, mitoxantrone, and dexamethasone (R-FND) followed by four weekly cycles of rituximab consolidation. Of these, 210 patients completed the planned treatment, and 202 responders were randomly assigned to rituximab maintenance (arm A) for 8 months, once every 2 months for a total of four doses, or to observation (arm B). Results Median ages in arms A and B were 66 and 65 years, respectively. After induction and consolidation therapy, the overall response rate was 86%, with 69% complete remissions (CR). After a 42-month median follow-up from diagnosis, 3-year progression-free survival (PFS; the primary end point) and overall survival (OS) were 66% (95% CI, 59% to 72%) and 89% (95% CI, 85% to 93%), respectively. After randomization, 2-year PFS was 81% for rituximab maintenance versus 69% for observation, with a hazard ratio of 0.74 (95% CI, 0.45 to 1.21; P = .226), although this was not statistically significant. No differences between the two arms were detected for OS. Overall, the regimen was well-tolerated. The most frequent grade 3 to 4 toxicity was neutropenia (25% of treatment courses), with 13 infections. Two toxic deaths (0.8%) occurred during induction treatment. Conclusion A brief R-FND induction plus rituximab consolidation achieved excellent results with high CR and PFS rates, supporting the feasibility of this regimen in patients older than 60 years. A short rituximab maintenance did not achieve a statistically significant PFS improvement over observation.

There is increasing interest in the potential influence of fetal and early life conditions on childhood wheezing.To investigate the associations between maternal complications and procedures in pregnancy and at birth and the risk of various wheezing phenotypes in young children.We studied 15,609 children, aged 6-7 yr, enrolled in a population-based study. Standardized questionnaires were completed by the children's mothers.Of the children, 9.5% (1,478) had transient early wheezing, 5.4% (884) had persistent wheezing, and 6.1% (948) had late-onset wheezing. Maternal hypertension or preeclampsia was associated with an increased risk of all three wheezing phenotypes (for transient early wheezing: odds ratio [OR], 1.40; 95% confidence interval [95% CI], 1.08-1.82; for persistent wheezing: OR, 1.59; 95% CI, 1.15-2.19; and for late-onset wheezing: OR, 1.47; 95% CI, 1.06-2.01). Use of antibiotics for urinary tract infections was associated with transient early wheezing (OR, 1.52; 95% CI, 1.16-2.00), whereas antibiotic administration at delivery was associated with both transient early wheezing (OR, 1.21; 95% CI, 1.01-1.46) and persistent wheezing (OR, 1.39; 95% CI, 1.10-1.75). Children who had a mother with diabetes were also more likely to have persistent wheezing (OR, 1.72; 95% CI, 0.99-3.00). Neither amniocentesis/chorionic villus sampling, nor weight gain in pregnancy, nor cesarean section was associated with the subsequent development of wheezing. Maternal asthma or atopy was not an effect modifier of the associations found.Some maternal complications during pregnancy and at delivery may increase the risk of developing different phenotypes of wheezing in childhood.

A retrospective, cross-sectional study was performed on a series of HCV-related mixed cryoglobulinemia (HCV-MC) patients to assess autonomic neuropathy (AN) and its relation to peripheral neuropathy (PN). Thirty consecutive patients affected by HCV-MC underwent clinical, neurological and electrodiagnostic examinations. Autonomic nervous system (ANS) involvement was assessed by functional cardiovascular tests and sympathetic skin response (SSR) evaluation. Sural nerve biopsy was performed in 10 patients with PN. All patients received steroids, 15 also received recombinant interferon-alpha2b (RIfn-alpha2b). PN occurred in 27 patients (90.0%) and AN in 4 (13.3 %) all with signs of PN. SSR was the autonomic test more frequently altered. Biopsy disclosed axonal degeneration more evident in the 4 patients with AN. Three out of 4 patients with AN received steroids and rIFN-alpha2b and 1 steroids alone. In our study on HCV-MC, it was concluded that AN can occur also without dysautonomic symptoms, SSR appears to be one of the optional tests to use together with dysautonomic tests to identify AN and finally PN and AN do not seem to be positively influenced by addition of rIFN-alpha2b to steroid treatment.

A consecutive sample of 76 chronic alcoholic patients was studied clinically, biochemically and electrophysiologically to assess clinical and/or subclinical signs of alcohol-related neuropathy as well as the most important and disputed risk factors for neuropathy such as age, parental history of alcoholism, nutritional status, alcoholic disease duration and total lifetime dose of ethanol (TLDE). The results show that alcohol-related neuropathy, especially when subclinical, seems to be frequent and mostly characterized by axonal degeneration of peripheral nerve fibres with earlier and more frequent involvement of sensory fibres and lower limbs. Moreover, positive family history of alcoholism, but above all alcoholic disease duration and TLDE, could be more important factors than malnutrition in determining neuropathy.