Search

Background: Pediatric residency in Italy has undergone significant changes in recent years, with a notable increase in the number of pediatric residents. Exploring the implications of this increase, highlighting disparities in training opportunities, and discussing the broader socio-economic impacts on pediatric healthcare, represent a crucial consideration for the healthcare system in the future. Main Body: The Italian National Association of Pediatric Residents ("Osservatorio Nazionale Specializzandi in Pediatria", ONSP) conducted an extensive survey among pediatric residents to assess the current state of pediatric residency. Key findings indicate that 50% of respondents believe the number of residents is excessive for the available training opportunities, leading to concerns about the quality of education and hands-on experience. Despite the increased number of residents, the workload has increased, but up to one-third of residents feel that the autonomy provided by their programs is insufficient. Significant disparities in training quality were found across different regions, with notable shortages in neonatology and pediatric emergency departments. Research opportunities are also limited, with only 17% of residents finding the time allocated to research satisfactory, especially in central and southern Italy. Conclusion: The increase in pediatric residents presents both challenges and opportunities. Addressing these challenges through strategic reforms, such as implementing standardized national curricula, investing in training resources and mobility programs, and enhancing research opportunities, is crucial for the future of pediatric residency in Italy. Ensuring high-quality training for all residents is an ethical and practical obligation that will significantly impact pediatric healthcare. [ABSTRACT FROM AUTHOR]

Background: The growing importance of psychological recovery for patients and their families following intensive care unit (ICU) experiences in recent years cannot be overemphasized. The ICU diary is used to aid patients in reducing the prevalence of post-traumatic stress disorder, anxiety, and depression. The usefulness of maintaining a diary during the grieving process has not yet been thoroughly investigated. Aim: To investigate the role of ICU diaries in the grief process experienced by family members of a person who died in the intensive care unit. Study Design: Nine family members of seven deceased ICU patients with an ICU diary were contacted and interviewed by phone using a semi-structured interview. A qualitative data analysis was performed using thematic synthesis. Setting: Italian general intensive care unit. Findings: Interviewed family members felt that the diary helped them during the grieving process. The return of diaries was desired by family members for support and to remember one's loved one. The diary helped them process their losses in various ways, including signs of evidence of care, emotional involvement, consideration, and coping with grief. Four main themes emerged from the analysis: writing the diary, reading the diary, talking about the diary, and the diary during the grieving process. Conclusions: The overall perception of the ICU diary was positive. The diary mostly helped relatives to "give back something of what we lost". This study also affirms the positive link between ICU diaries and bereavement in Italian ICU. Further studies are required to confirm the usefulness of this tool in the grieving process. Relevance to Clinical Practice: The ICU diary can help patients' family members understand what happened to their loved one and play an important role in the grieving process. The diary served as a valuable source of information that aided in providing bereavement support to the family by helping them to gain a rational and emotional understanding of the patient's death. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we drew up the growth charts of Italian patients with Shwachman–Diamond syndrome (SDS) at ages 0 to 18 years. We found that the 50th and 3rd percentiles of weight and height of the pediatric general population correspond to the 97th and 50th percentiles of patients with SDS, respectively. The median age at menarche in females with SDS was comparable with that of the general population. The percentage increment in weight of subjects aged 14–18 years was higher in patients with SDS than in the general population. This study provides insight into the potential usefulness of SDS-specific growth chart data as a resource for clinicians working with patients with SDS. Shwachman–Diamond syndrome (SDS) is one of the most common inherited bone marrow failure syndromes. SDS is characterized by hypocellular bone marrow, with a severe impairment of the myeloid lineage, resulting in neutropenia, thrombocytopenia, and, more rarely, anemia. Almost 15% of patients with SDS develop myelodysplastic syndrome or acute myeloid leukemia as early as childhood or young adulthood. Exocrine pancreatic insufficiency is another common feature of SDS. Almost all patients with SDS show failure to thrive, which is associated with skeletal abnormalities due to defective ossification. Considering these observations, it remains unfeasible to use the common growth charts already available for the general population. To address this issue, we report how we drew up growth charts of patients with SDS aged 0 to 18 years. We analyzed height, weight, and body max index (BMI) in 121 Italian patients with SDS. Results indicated that the 50th and 3rd percentiles of weight and height of the pediatric general population correspond to the 97th and 50th percentiles of patients with SDS aged 0–18 years, respectively. In addition, the percentage increment in weight of subjects aged 14–18 years was higher in patients with SDS than in the general population. SDS-specific growth charts, such as those described here, afford a new tool, which is potentially useful for both clinical and research purposes in SDS. [ABSTRACT FROM AUTHOR]

Achalasia is a rare esophageal motility disorder of unknown etiology. With the ageing of the general population, treatment in elderly patients has become increasingly common; however, the gold standard treatment in this population remains unclear. The aim of this study was to evaluate the outcomes of laparoscopic Heller-Dor myotomy (LHM) in geriatric patients. In this study, consecutive achalasia patients undergoing LHM at the University Hospital 'Federico II' of Naples from November 2018 to November 2022 were prospectively enrolled. Patients were divided into two groups based on their age at intervention: elderly (≥70 years) and younger (<70 years). The two study groups were compared by minimizing the different distribution of covariates through a propensity score matching analysis (PSM). In both populations, there was a significant improvement in terms of manometric parameters and symptoms after surgery. After applying one-on-one PSM, we obtained a total population of 48 achalasia patients divided into two groups (24 patients each). No significant differences were found in terms of demographic characteristics as well as preoperative and intraoperative variables between two groups. At 12 months from surgery, integrated relaxation pressure (IRP) was significantly lower in patients ≥ 70 years (p = 0.032), while younger patients scored significantly less at the post-operative Eckardt score (p = 0.047). Laparoscopic Heller-Dor myotomy is a safe and effective treatment even in elderly patients with rapid post-operative recovery, improvement of symptoms and manometric parameters. [ABSTRACT FROM AUTHOR]

To provide clinical characteristics and to quantify the number of patients receiving the extemporaneous combination of the calcium channel blocker amlodipine and the angiotensin converting enzyme inhibitor zofenopril in a real-world setting. This evidence can provide a snapshot of the potential users of the two molecules in a single pill combination (SPC). Retrospective observational study using data from the IQVIA Italian Longitudinal Patient Database. Adult patients firstly prescribed with amlodipine and zofenopril between 1 July 2011 and 30 June 2020 were identified and demographic and clinical characteristics were extracted. Treatment adherence was evaluated as proportion of days covered (PDC). The potential number of patients eligible for a SPC was calculated. A population of 2394 hypertensive patients, mean age of 68.6 years ±12.7, 52.6% male were treated with amlodipine and zofenopril. The majority of patients (54.5%) were low adherent (PDC <40%), 25.9% were intermediate adherent and only 19.6% were high adherent (>80%) to therapy. Around 42,500 adult hypertensive patients were estimated to be prescribed the extemporaneous combination in 2019 in Italy, being potentially eligible for treatment with amlodipine and zofenopril SPC. The administration of the extemporaneous combination of zofenopril and amlodipine in hypertensive patients is a common practice in Italy. The development of a SPC can be a viable treatment option to simplify therapy and to increase adherence in hypertensive patients who are already on the two monotherapies in combination. [ABSTRACT FROM AUTHOR]

Providing evidence on donepezil and memantine administration as extemporaneous combination (DM-EXT) to treat Alzheimer Disease (AD) in Italy, and describing demographic and clinical features of AD patients prescribed DM-EXT. Retrospective observational study using IQVIA Italian LifeLink Treatment Dynamics (LRx) and Longitudinal Patient Database (LPD). Prevalent users of DM-EXT were identified on the databases (cohorts DMpLRx and DMpLPD) including patients with donepezil and memantine overlapping prescriptions during the selection period (DMpLRx: "July 2018–June 2021"; DMpLPD: "July 2012–June 2021"). Demographic and clinical profiles of patients were provided. Starting from cohort DMpLPD, new users of DM-EXT were selected to calculate treatment adherence. Three additional cohorts of prevalent users of DM-EXT were identified on IQVIA LRx over subsequent 12-month periods, from July 2018 to June 2021, to get national-level yearly estimates accounting for database representativeness. Cohorts DMpLRx and DMpLPD included 9862 and 708 patients, respectively. For both cohorts, two-third of patients were female, and more than half were aged 80+. Concomitant conditions and co-treatments prevalence was very high; most frequent comorbidities included psychiatric and cardiovascular diseases. An intermediate-to-high adherence was observed in 57% of DM-EXT new users. National-level yearly estimates showed an increasing trend (+4%) in DM-EXT prescription, which led to estimate about 10,000 patients being treated during the period "July 2020–June 2021". Prescription of DM-EXT is a common practice in Italy. Because the administration of fixed-dose (FDCs) instead of extemporaneous combinations improves treatment adherence, the introduction of an FDC containing donepezil and memantine might enhance AD patients' management and reduce caregiver burden. [ABSTRACT FROM AUTHOR]

Introduction: T1DM is the most frequent form of diabetes in children. It has a multifactorial pathogenesis in which genetic, environmental and immunological factors are involved. Among genetic explanations a major role is attributed to second class HLA genes, with the greatest risk associated with the simultaneous presence of the haplotypes DR3DQ2 and DR4DQ8. Based on results obtained in other countries, the aim of this research is to verify a possible association between the haplotype DRB1 * 04: 05-DQA1 * 03-DQB1 * 02 and the onset of T1DM among Italian children with possible genotype-phenotype correlations. Greater knowledge of genes which increase or decrease susceptibility is important for genome analysis. Materials and methods: 165 patients with type 1 diabetes treated at the Diabetology Unit of the Meyer Children's University Hospital, were clinically analyzed. Data relating to age at diagnosis, pancreatic anti-beta cell autoimmunity, comorbidities with date of diagnosis and family history were retrospectively collected from medical data. A case-control study was conducted to investigate the HLA types of the patients compared to a control group of 819 Tuscan donors enrolled in the National Bone Marrow Donor Register. Typing was carried out using the Eurospital "DIABEGEN" kit, currently in use at the immunology laboratory of the Meyer Children's University Hospital. Results: Mean age at diagnosis was 9.3 years; most children (97%) had anti-pancreatic beta cell autoimmunity; the anti-insulin antibody (IAA) was more frequent among children with early clinical disease onset (0–5 years of age). From the case control comparison performed on HLA typing, it emerged that the greatest risk for the development of type 1 diabetes is conferred by the haplotypes DR3DQ2 and DR4DQ8, but in addition to these haplotypes, already known in other countries, we identified another haplotype, DR4DQ2 (DRB1 * 04: 05-DQA1 * 03-DQB1 * 02) which appears to predispose children to type 1 diabetes (p value 2.80E-08) and it is associated with early clinical disease onset (p-value = 0.002). Conclusions: We report a new haplotype which increases susceptibility to type 1 diabetes among Italian children and which is associated with early clinical disease onset. Given the central role attributed to genetic factors in the pathogenesis of T1DM and to the II class HLA genes, this new haplotype ought to be recognized as a risk factor and included in tests routinely carried out to identify patients with a genetic predisposition to type I diabetes in Italy. These findings could have practical implications in research and prevention programs. [ABSTRACT FROM AUTHOR]

Clinically describing hypertensive patients initiating nebivolol/zofenopril extemporaneous combination (NZ-EXC) and estimating the number of patients currently receiving NZ-EXC and of those potentially eligible for the fixed-dose combination of the two molecules (NZ-FDC) in Italy. This retrospective observational study used data from IQVIA Italian Longitudinal Patient Database (LPD). Adult hypertensive patients firstly prescribed NZ-EXC between 1 July 2011 and 30 June 2020 were identified and their demographic and clinical characteristics were extracted. Treatment adherence was evaluated as proportion of days covered (PDC) and classified as low (PDC <40%), intermediate (PDC ≥40% and <80%) or high (PDC ≥80%). Two additional cohorts were identified in 2019 to provide the national-level yearly estimates of patients prescribed NZ-EXC and of patients eligible for NZ-FDC. In total 1745 patients were prescribed NZ-EXC: 60% were women; mean age was 65 years. The most frequent comorbidities were dyslipidemia (19.0%), diabetes (15.5%) and thyroid diseases (13.1%); the most common co-prescribed treatments were antithrombotics (29.1%), lipid-lowering agents (28.8%), nonsteroidal anti-inflammatory drugs (26.1%) and antihyperglycemic agents (13.5%). Mean PDC was 39%, and 57% of the patients had a PDC < 40%. The yearly estimate of patients prescribed NZ-EXC in 2019 was 59,000, while potential users of NZ-FDC were estimated to be 29,000. NZ-EXC in hypertensive patients is a common practice in Italy and the development of a NZ-FDC can be a viable treatment option for hypertensive patients who are already receiving nebivolol and zofenopril through the concomitant assumption of two distinct pills. As supported by scientific literature, FDCs of antihypertensive drugs could simplify treatment, improve adherence and potentially reduce health-care costs as related to a better control of blood pressure. [ABSTRACT FROM AUTHOR]

Circadian clocks help animals to be active at the optimal time of the day whereby for most species the daily light-dark cycle is the most important zeitgeber for their circadian clock. In this respect, long arctic summer days are particularly challenging as light is present almost 24 h per day, and continuous light makes the circadian clocks of many animals arrhythmic. This is especially true for the fruit fly, Drosophila melanogaster, which possesses a very light-sensitive clock. The blue-light photoreceptor Cryptochrome (CRY) and the clock protein Timeless (TIM) are the light-sensitive components of the circadian clock and are responsible for constant light-induced arrhythmicity even at very low light intensities. Nevertheless, D. melanogaster was able to spread from its tropical origin and invade northern latitudes. Here, we tested whether a natural polymorphism at the timeless (tim) locus, s-tim and ls-tim, helped adaptation to very long photoperiods. The recently evolved natural allele, ls-tim, encodes a longer, less light sensitive form of TIM (L-TIM) in addition to the shorter (S-TIM) form, the only form encoded by the ancient s-tim allele. ls-tim has evolved in southeastern Italy and slowly spreads to higher latitudes. L-TIM is known to interact less efficiently with CRY as compared with S-TIM. Here, we studied the locomotor activity patterns of ~40 wild s-tim and ls-tim isofemale lines caught at different latitudes under simulated high-latitude summer light conditions (continuous light or long photoperiods with 20-h daily light). We found that the ls-tim lines were significantly more rhythmic under continuous light than the s-tim lines. Importantly, the ls-tim lines can delay their evening activity under long photoperiods, a behavioral adaptation that appears to be optimal under high-latitude conditions. Our observations suggest that the functional gain associated with ls-tim may drive the northern spread of this allele by directional selection. [ABSTRACT FROM AUTHOR]

The spittlebug Philaenus spumarius L. (Hemiptera: Aphrophoridae) is the predominant vector of Xylella fastidiosa Wells et al. (Xanthomonadales: Xanthomonadaceae) (Xf) to olive trees in the Apulia Region in Italy. Previous studies focused on assessing the Xf transmission efficiency of spittlebugs and the natural infectivity of the P. spumarius populations. However, the factors that influence Xf transmission by P. spumarius to olive are still largely unknown, and these knowledge gaps hamper the comprehension of the epidemiology of emerging Xf-associated diseases. We have performed two sets of experiments to study the transmission biology of Xf by P. spumarius to understand the kinetics of the bacterial persistence, transmission efficiency and the spread rate of Xf among olive trees in summer and autumn. The results show that i) P. spumarius is a competent Xf vector to olive plants throughout its adult life, ii) the bacterial load in the foregut of the vector increases during the first 2-3 weeks after acquisition and then becomes stable, iii) the transmission rates may vary significantly during the year and under different climatic conditions, and iv) the differential survival of vectors -- which is influenced by the age of the insects, the season and climatic conditions -- may affect the spread of Xf in olive plants. These results will help to improve both the modelling of the spread of the pathogen, by allowing the effect of the insect vectors to be explicitly incorporated, and the design of effective control and prevention measures against this vector-borne disease. [ABSTRACT FROM AUTHOR]

The aim of this work was to evaluate the susceptibility to flavescence dorée (FD) of 12 Vitis vinifera cultivars grown in Piedmont, and representative of the wine‐making tradition of this area. The experiments were conducted under controlled conditions to ensure constant infection pressure. Test plants were ex vitro potted vines, singly inoculated with four Scaphoideus titanus infected by FD‐C phytoplasma (FDp), under greenhouse conditions. Vines were tested for FDp at 5 and 8 weeks postinoculation (wpi) and the phytoplasma load was measured in leaves and roots at 8 wpi. Within the 14 V. vinifera accessions (belonging to 12 cultivars), three susceptibility clusters were identified. Cultivars within the low susceptibility group showed low phytoplasma loads and low percentages of infected plants, suggesting a tolerant behaviour. To confirm these results, four Vitis cultivars, representing extremes of FD susceptibility from low to high, were grafted onto Kober 5BB rootstocks and inoculated with laboratory‐infected S. titanus, under semi‐field conditions. The transmission experiments onto grafted cuttings confirmed that susceptibility to the disease depends on the scion genotype. The data indicated that none of the tested V. vinifera genotypes are resistant to FD, although some cultivars with low susceptibility are available, and can be explored for identifying genetic traits involved in disease tolerance/resistance. Moreover, ranking Vitis genotypes for their susceptibility to FD is in itself a valuable tool to support vine growers in their decision management, by helping them to choose the most appropriate varieties according to their specific FD epidemiological contexts. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency is a major cause of anemia in older people. Increasing the knowledge on the predictors of iron-deficiency anemia (IDA) may facilitate its timely diagnosis. Aim: To investigate the predictors of IDA in older people in four European countries. Design and Setting: Retrospective longitudinal study. Primary care patients aged 65 or older (N = 24,051) in four European countries. Methods: IDA predictors were estimated using multivariate Cox regression based on information gathered from national primary care databases: Italy (years 2002–2013), Belgium, Germany and Spain (years 2007–2012). Adjusted hazard ratios (aHR) with 95% confidence intervals (CIs) were estimated. Results: In Spain and Belgium, men were at greater risk of IDA than women, while they had a lower risk in Italy. Weakness, irritability, alopecia and xerostomia were signs and symptoms significantly associated with IDA. Concurrent diseases, potential causes of anemia, positively associated with IDA were small bowel polyposis, stomach cancer, obesity, gastritis and peptic ulcer, esophagitis, Crohn's disease, celiac disease, lymphangiectasis, gastrectomy or gastric atrophy, gut resection or bypass, and cardiac prosthetic valve. Aspirin users had a 12–35% higher hazard of IDA than non-users. Similarly, corticosteroids and anti-acids were positively associated with IDA. A higher level of comorbidity was associated with an increased hazard of IDA in all countries. Conclusions: Specific signs and symptoms, chronic conditions, a greater comorbidity burden, and specific pharmacological treatments registered in primary care databases represent relevant predictors and correlates of incident IDA in older people in Europe. General practitioners might employ this information to obtain early diagnosis of IDA in community-dwelling older adults. [ABSTRACT FROM AUTHOR]

Introduction: Italian law mandates that every competitive athlete must undergo annual preparticipation evaluation (PPE) to identify cardiovascular (CV) diseases that pose a risk of sudden death (SD) during sport and other conditions that may threaten the athlete's health. We investigated the diagnostic yield, rate of disqualification and costs of our PPE.Methods: We included 5910 consecutive apparently healthy athletes (61% males, mean age 15±4 years) who underwent annual PPE performed by a sports medicine specialist. The PPE included history, physical examination, weight, height and blood pressure measurement, test of visual acuity, spirometry, urine chemistry, resting 12-lead ECG and exercise testing with ECG monitoring. In cases of abnormal findings, we carried out second-line investigations.Results: During a 12-month study period, 5.326 (90.2%) athletes were cleared for competition after a normal first-line evaluation and 584 (9.8%) underwent one or more further examinations. Of those, 88 (1.5%) were diagnosed to have a CV disease (including 18 (0.3%) at-risk of SD) and 31 (0.5%) had a non-CV diagnosis. A total of 32 (0.5%) athletes were temporarily (n=15) or permanently (n=17) disqualified from competitive sports. The average cost per athlete was €79, which consisted of €64 (80%) for first-line evaluations and €15 (20%) for additional investigations.Conclusion: PPE according to the Italian model identified a range of diseases in 2.0% of apparently healthy athletes at an average cost of €79. [ABSTRACT FROM AUTHOR]

The Toarcian Oceanic Anoxic Event (T-OAE) interval was cored at Colle di Sogno and Gajum in the Lombardy Basin (Southern Alps, northern Italy). The Sogno and Gajum cores recovered 26.83 and 31.18 stratigraphic metres, respectively, of pelagic sediments consisting of marly limestones, marlstone, marly claystone, and black shale. Drilling at both sites resulted in 100 % recovery of unweathered material. The pelagic succession comprises a relatively expanded black shale interval of 4.98 m in the Sogno core and 15.35 m in the Gajum core, with lower and upper boundaries without evidence of hiatuses. The Sogno and Gajum cores can be considered reference sections for the pelagic lower Toarcian interval of the western Tethys and will provide high-resolution micropaleontological, inorganic and organic geochemical, isotopic multiproxy data. Integrated stratigraphy and cyclostratigraphy are predicted to result in estimates of durations and rates to model the ecosystem resilience to the extreme perturbations of the T-OAE and gain a better understanding of current global changes and help provide better projections of future scenarios. [ABSTRACT FROM AUTHOR]

Background: Mutations in the LMNA (lamin A/C) gene have been associated with neuromuscular and cardiac manifestations, but the clinical implications of these signs are not well understood.Objective: To learn more about the natural history of LMNA-related disease.Design: Observational study.Setting: 13 clinical centers in Italy from 2000 through 2018.Patients: 164 carriers of an LMNA mutation.Measurements: Detailed cardiologic and neurologic evaluation at study enrollment and for a median of 10 years of follow-up.Results: The median age at enrollment was 38 years, and 51% of participants were female. Neuromuscular manifestations preceded cardiac signs by a median of 11 years, but by the end of follow-up, 90% of the patients had electrical heart disease followed by structural heart disease. Overall, 10 patients (6%) died, 14 (9%) received a heart transplant, and 32 (20%) had malignant ventricular arrhythmias. Fifteen patients had gait loss, and 6 had respiratory failure. Atrial fibrillation and second- and third-degree atrioventricular block were observed, respectively, in 56% and 51% of patients with combined cardiac and neuromuscular manifestations and 37% and 33% of those with heart disease only.Limitations: Some of the data were collected retrospectively. Neuromuscular manifestations were more frequent in this analysis than in previous studies.Conclusion: Many patients with an LMNA mutation have neurologic symptoms by their 30s and develop progressive cardiac manifestations during the next decade. A substantial proportion of these patients will have life-threatening neurologic or cardiologic conditions.Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Iron-deficiency anemia (IDA) was the main condition contributing to higher rates of years lived with disabilities in women in 2016. To date, few studies have investigated gender differences in determinants of IDA in Europe. The aim of the present study was to evaluate the determinants of IDA among females and males in four European countries. IDA determinants were estimated using multivariable Cox regression based on information gathered from national primary care databases, namely Italy (for years 2002-2013), Belgium, Germany, and Spain (for years 2007-2012). Adjusted hazard ratios (aHR) with 95% confidence intervals (CIs) were estimated. Age was significantly associated with IDA in females of childbearing age in all four countries, as well as pregnancy, for which the aHR ranged from 1.20 (95% CI 1.15-1.25) in Italy to 1.88 (95% CI 1.53-2.31) in Germany. In males, the aHR increased with age starting from the 65-69 age group. Menometrorrhagia was associated with IDA in Germany (aHR 2.71, 95% CI 1.96-3.73), Italy (aHR 1.80, 95% CI 1.60-2.03), and Spain (aHR 1.52, 95% CI 1.31-1.76). A greater risk for women with alopecia was also observed. Weakness and headache indicated a higher risk in both men and women. Patients with diseases characterized by blood loss or gastrointestinal malabsorption were also at significantly increased risk. Physicians should encourage women of childbearing age to adhere to dietary recommendations regarding iron intake and regularly prescribe screening of iron status. Upper and lower gastrointestinal investigations should be recommended for patients with a confirmed diagnosis of IDA. [ABSTRACT FROM AUTHOR]

Myasthenia gravis is a well-treatable disease, in which a prompt diagnosis and an adequate management can achieve satisfactory control of symptoms in the great majority of patients. Improved knowledge of the disease pathogenesis has led to recognition of patient subgroups, according to associated antibodies, age at onset and thymus pathology, and to a more personalized treatment. When myasthenia gravis is suspected on clinical grounds, diagnostic confirmation relies mainly on the detection of specific antibodies. Neurophysiological studies and, to a lesser extent, clinical response to cholinesterase inhibitors support the diagnosis in seronegative patients. In these cases, the differentiation from congenital myasthenia can be challenging. Treatment planning must consider weakness extension and severity, disease subtype, thymus pathology, together with patient characteristics and comorbidities. Since most subjects with myasthenia gravis require long-term immunosuppressive therapy, surveillance of expected and potential adverse events is critical. For patients refractory to conventional immunosuppression, the use of biologic agents is highly promising. These recommendations are addressed to non-experts on neuromuscular transmission disorders. The diagnostic procedures and therapeutic approaches hereafter described are largely accessible in Italy. [ABSTRACT FROM AUTHOR]

Background: A small number of patients affected by Neutral Lipid Storage Diseases (NLSDs: NLSD type M with Myopathy and NLSD type I with Ichthyosis) have been described in various ethnic groups worldwide. However, relatively little is known about the progression and phenotypic variability of the disease in large specific populations. The aim of our study was to assess the natural history, disability and genotype-phenotype correlations in Italian patients with NLSDs. Twenty-one patients who satisfied the criteria for NLSDs were enrolled in a retrospective cross-sectional study to evaluate the genetic aspects, clinical signs at onset, disability progression and comorbidities associated with this group of diseases.Results: During the clinical follow-up (range: 2-44 years, median: 17.8 years), two patients (9.5%, both with NLSD-I) died of hepatic failure, and a further five (24%) lost their ability to walk or needed help when walking after a mean period of 30.6 years of disease. None of the patients required mechanical ventilation. No patient required a heart transplant, one patient with NLSD-M was implanted with a cardioverter defibrillator for severe arrhythmias.Conclusion: The genotype/phenotype correlation analysis in our population showed that the same gene mutations were associated with a varying clinical onset and course. This study highlights peculiar aspects of Italian NLSD patients that differ from those observed in Japanese patients, who were found to be affected by a marked hypertrophic cardiopathy. Owing to the varying phenotypic expression of the same mutations, it is conceivable that some additional genetic or epigenetic factors affect the symptoms and progression in this group of diseases. [ABSTRACT FROM AUTHOR]

The Italian debate about the role of clinical ethics and ethics consultation has brought about the need to create a working group of Healthcare Ethics Consultation. The group began to take shape and to be organized in 2010; its activities are largely directed to share experiences, to analyze this field and to develop a professional profile of the clinical ethicist recognized throughout the nation. The working group of Clinical Ethics and Healthcare Ethics Consultation was born from some meetings and the group started to draft a Document about Clinical Ethics Consultation in Healthcare in Rome (June 2013). The Document was approved in Trento at the Kessler Foundation (October 2013) and undersigned by more than 200 people. The newborn document was called “The Document of Trento”: it is the first Italian document regarding clinical ethics consultation. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to investigate the proportion of physicians and nurses who agree with the administration of antibiotic therapy (AT), artificial hydration (AH), and artificial nutrition (AN) in patients with advanced dementia and different life expectancies. Furthermore, we aimed at analyzing the correlates of the opinion according to which medical treatments should no longer be given to advanced dementia patients once their life expectancy falls. Methods: End-of-life decisions and opinions were measured with a questionnaire that was sent to geriatric units, hospices and nursing homes in three different regions of Italy. Multivariate logistic regressions were carried out to ascertain the correlates of the agreement with the administration of AH, AT or AN. Results: When the patient's life expectancy was 1-6 months, 83% of respondents agreed with AH, 79% with AT and 71% with AN. When the life expectancy was less than 1 month, a large proportion of respondents still agreed with AH and AT (73% and 61%), whereas less than one in two respondents (48%) agreed with AN. Conclusions: The findings of the present study showed that AN creates more ethical dilemmas in the clinical management of end of life than other treatments, such as AH or AT. Opinions on whether or not these practices are appropriate at the end of life were related with feelings, thoughts and ethical issues that played a different part for physicians and nurses. Geriatr Gerontol Int 2017; 17: 487-493. [ABSTRACT FROM AUTHOR]

The world population is demonstrating an increasing awareness about the ecological impacts of air quality, including impacts on human health. The Veneto region and, more generally, the Po Valley (NE Italy), are characterised by frequent exceedance of limit values for air quality, in particular particulate matter (PM 10), which causes these areas to be listed as hotspots; thus, this region has some of the worst air pollution in Europe. The aim of the current research was to analyse a 10 year-long time series of air quality data (2011–2021) in the Veneto region to investigate the influence of selected factors on air quality, such as natural processes (meteorological conditions), environmental policies, and health emergency measures due to the COVID-19 pandemic. Generally, the considered pollutants, PM 10 , NO, and NO 2 , presented a decreasing trend during the last ten years. The reduction in nitrogen oxides was clearly improved after the implementation of a specific environmental protocol (the "New Agreement of Po Valley Basin"). Conversely, the PM 10 concentration seemed to be affected by other important emission sources, such as domestic heating systems, agricultural activities, and animal farms, which are not as strongly regulated as emission sources such as traffic. The 2020 lockdown mainly influenced nitrogen oxide concentrations. • Italy has infringed on the EU law regarding ambient air quality. • One of the more polluted Italian areas is the Po Valley, including the Veneto region. • A long time series of the air quality data region was statistically analysed. • Only nitrogen oxide concentrations were significantly reduced during the last ten years. • Environmental policies have mainly addressed traffic emissions. [ABSTRACT FROM AUTHOR]

Flavescence dorée (FD) is a threat for wine production in the vineyard landscape of Piemonte, Langhe-Roero and Monferrato, Italy. Spread of the disease is dependent on complex interactions between insect, plant and phytoplasma. In the Piemonte region, wine production is based on local cultivars. The role of six local grapevine varieties as a source of inoculum for the vector Scaphoideus titanus was investigated. FD phytoplasma (FDP) load was compared among red and white varieties with different susceptibility to FD. Laboratory-reared healthy S. titanus nymphs were caged for acquisition on infected plants to measure phytoplasma acquisition efficiency following feeding on different cultivars. FDP load for Arneis was significantly lower than for other varieties. Acquisition efficiency depended on grapevine variety and on FDP load in the source plants, and there was a positive interaction for acquisition between variety and phytoplasma load. S. titanus acquired FDP with high efficiency from the most susceptible varieties, suggesting that disease diffusion correlates more with vector acquisition efficiency than with FDP load in source grapevines. In conclusion, although acquisition efficiency depends on grapevine variety and on FDP load in the plant, even varieties supporting low FDP multiplication can be highly susceptible and good sources for vector infection, while poorly susceptible varieties may host high phytoplasma loads. [ABSTRACT FROM AUTHOR]

Objective: To carry out a deep characterisation of the main androgen-responsive tissues involved in spinal and bulbar muscular atrophy (SBMA).Methods: 73 consecutive Italian patients underwent a full clinical protocol including biochemical and hormonal analyses, genitourinary examination, bone metabolism and densitometry, cardiological evaluation and muscle pathology.Results: Creatine kinase levels were slightly to markedly elevated in almost all cases (68 of the 73; 94%). 30 (41%) patients had fasting glucose above the reference limit, and many patients had total cholesterol (40; 54.7%), low-density lipoproteins cholesterol (29; 39.7%) and triglyceride (35; 48%) levels above the recommended values. Although testosterone, luteinising hormone and follicle-stimulating hormone values were generally normal, in one-third of cases we calculated an increased Androgen Sensitivity Index reflecting the presence of androgen resistance in these patients. According to the International Prostate Symptom Score (IPSS), 7/70 (10%) patients reported severe lower urinal tract symptoms (IPSS score >19), and 21/73 (30%) patients were moderately symptomatic (IPSS score from 8 to 19). In addition, 3 patients were carriers of an indwelling bladder catheter. Videourodynamic evaluation indicated that 4 of the 7 patients reporting severe urinary symptoms had an overt prostate-unrelated bladder outlet obstruction. Dual-energy X-ray absorptiometry scan data were consistent with low bone mass in 25/61 (41%) patients. Low bone mass was more frequent at the femoral than at the lumbar level. Skeletal muscle biopsy was carried out in 20 patients and myogenic changes in addition to the neurogenic atrophy were mostly observed.Conclusions: Our study provides evidence of a wide non-neural clinical phenotype in SBMA, suggesting the need for comprehensive multidisciplinary protocols for these patients. [ABSTRACT FROM AUTHOR]

Objective: Differently than Schizophrenia, the investigation of cognitive impairment in bipolar disorder and major depressive disorder (MDD) attracted the interest of research only recently. Therefore, it is worth understanding clinicians’ perception about cognitive dysfunction in MDD and raising awareness about this issue.Methods: Between December 2014 and January 2015, 128 Italian psychiatrists participated in an on-line survey aiming at understanding psychiatrists’ perception about cognitive symptoms in MDD. The questionnaire comprised three sections: the first investigating psychiatrists’ socio-demographic profile, the second assessing cognitive symptoms relevance without mentioning that they represented the study focus and the third explicitly investigating cognitive symptoms.Results: Cognitive symptoms were considered as a relevant dimension of MDD and appeared among the most frequently cited residual symptoms influencing patients’ work and relapse risk. About 70% of psychiatrists declared that cognitive symptoms significantly influence antidepressant choice. However, in the second questionnaire section cognitive symptoms appeared less frequently considered for antidepressant choice.Conclusions: Results revealed a clear understanding of cognitive symptoms relevance in MDD. Nevertheless, the discrepancy between psychiatrists’ perception and their therapeutical choices underlines the presence of an unmet-need that should be addressed increasing the awareness about the positive effects on cognitive symptoms of existing drugs, which could allow a more symptom-oriented therapeutical intervention.Key pointsMajor depressive disorder (MDD) is a common mental disorder often associated with deficits in cognitive function.Psychiatrists considered cognitive symptoms among the most relevant residual symptoms in MDD patients that compromise patients working and influence the relapse risk.The importance given to residual cognitive symptoms seemed not to be reflected by psychiatrists’ therapeutical choice.There is a gap between what psychiatrists know and what psychiatrists apply to their clinical practice reflecting the feeling of a therapeutical unmet need. [ABSTRACT FROM PUBLISHER]

Background: Although their benefits are controversial, artificial nutrition and hydration are often administered as a form of basic care to terminally ill patients. An important reason for this may be that these treatments have strong emotional and psychological meanings. Aims: In the present article we investigated the opinions of Italian physicians and nurses on the administration of artificial nutrition and hydration to terminally ill patients with advanced dementia. We also investigated the antecedents of these opinions, considering feelings and thoughts related to death, ethical issues and training in palliative care. Method: A questionnaire was administered to Italian physicians ( n=288) and nurses ( n=763). We analyzed the percentages of agreement with the administration of artificial nutrition and hydration and, using multivariate logistic regressions, the possible antecedents of these opinions. Results: Agreement with the provision of artificial hydration was higher (73%) than for artificial nutrition (48%), suggesting that artificial hydration may be seen as a form of basic care. Agreement with their administration was generally lower among professionals in northern Italy working in geriatrics wards who had received training in palliative care. We also found that death-related feelings and thoughts and ethical issues played a different part for physicians and nurses. Conclusions: Our findings suggest that opinions concerning artificial nutrition and hydration not only derive from scientific background, but also relate to cultural, ethical, and psychological issues. Our results also reveal important differences between physicians' and nurses' opinions, providing useful information for interpreting and overcoming obstacles to the effective cooperation between these professionals. [ABSTRACT FROM AUTHOR]

Background and aims: In Italy there is a paucity of empirical data on practices concerning end- of-life decisions (ELDs) in geriatrics. We aimed to investigate the frequency and characteristics of ELDs made by Italian physicians and nurses in the geriatric setting. Methods: In 2009, an anonymous questionnaire was sent to 54 geriatric units, 21 hospices, and 382 nursing homes in the Véneto and Trentino Alto Adige regions, and to professionals in the area who are members of the Italian Gerontology and Geriatrics Association. Results: This paper reports the results of 552 questionnaires answered by 171 physicians, 368 nurses and 13 professionals who did not state their profession. Death was preceded by decisions to start or continue treatments likely to prolong the patients' life in 51.3% of cases. The proportion of deaths preceded by a decision to end life (DEL) was 20.8%; 18% of DELs concerned non-treatment decisions. There were 9 cases of ending of life without patient's explicit request. No cases of doctor-assisted suicide were reported, while there were 2 cases of euthanasia, one reported by a physician and one by a nurse. Conclusion: In geriatrics, DELs often precede the deaths of terminally-ill Italian patients. Nurses report making DELs more often than physicians, especially in incompetent patients. Continuous deep sedation was adopted by 39.5% of the Italian physicians for deaths not occurring suddenly and unexpectedly. Our report on physicians' and nurses' experiences of ELD making in geriatric settings can offer a valuable contribution to the current debate on end-of-life treatment, an issue that goes beyond national borders. [ABSTRACT FROM AUTHOR]

Abstract: Background: A substantial proportion of patients with neuromuscular disease (NMD) who undergo positive pressure ventilation via endotracheal intubation for acute respiratory failure fail to pass spontaneous breathing trials and should be considered at high risk for extubation failure. In our study, we prospectively investigated the efficacy of early application of noninvasive ventilation (NIV) combined with assisted coughing as an intervention aimed at preventing extubation failure in patients with NMD. Methods: This study is a prospective analysis of the short-term outcomes of 10 patients with NMD who were treated by NIV and assisted coughing immediately after extubation and comparison with the outcomes of a population of 10 historical control patients who received standard medical therapy (SMT) alone. The participants were composed of 10 patients with NMD who were submitted to NIV and assisted coughing after extubation (group A) and 10 historical control patients who were administered SMT (group B), who were admitted to a 4-bed respiratory intensive care unit (RICU) in a university hospital. Need for reintubation despite treatment was evaluated. Mortality during RICU stay, need for tracheostomy, and length of stay in the RICU were also compared. Results: Significantly fewer patients who received the treatment protocol required reintubation and tracheostomy compared with those who received SMT (reintubation, 3 vs 10; tracheostomy, 3 vs 9; P = .002 and .01, respectively). Mortality did not differ significantly between the 2 groups. Patients in group A remained for a shorter time in the RICU compared with group B (7.8 ± 3.9 vs 23.8 ± 15.8 days; P = .006). Conclusions: Preventive application of NIV combined with assisted coughing after extubation provides a clinically important advantage to patients with NMD by averting the need for reintubation or tracheostomy and shortening their stay in the RICU; its use should be included in the routine approach to patients with NMD at high risk for postextubation respiratory failure. [Copyright &y& Elsevier]

Aim: A retrospective survey was performed to identify factors predicting functional recovery in an elderly population admitted to a subacute care nursing home for rehabilitation treatment (abbreviated RSA. from the Italian: "Residenza Sanitaria Assistenziale"). Methods: Demographic data (age and sex), clinical features (type of disease at admission, length of stay in RSA, Barthel Index (Bl) at admission and discharge, duration of rehabilitation treatment and destination at discharge) were extracted from the medical records of 551 subjects. Multiple logistic regression was used to assess relationships between functional outcome on the Bl and predictive variables. Results: Of all subjects, 239 (43.3%) had neurological, 214 (38.8%) orthopaedic and 98 (17.7%) internal disorders. On discharge from the RSA, subjects with orthopedic and internal diseases showed significantly greater functional improvement than those with neurological disorders (p<0.0001). Multivariate analysis showed that the independent variables related to functional recovery on the Bl were pathology (orthopedic and internal diseases), Bl (≤32) score at RSA admission, and duration of rehabilitation treatment (≥30 sessions). Conclusion: Our results may help to optimize management of older adults admitted to an RSA for rehabilitation treatment. [ABSTRACT FROM AUTHOR]

Background and purpose: Several studies have reported an increase in ALS incidence in recent years but population-based studies in Europe do not confirm this trend. To analyze ALS incidence over time we conducted a retrospective incidence study in the Padova district of Italy (1992 to 2005). We had previously conducted a survey in the same area in the years 1980–1991. Methods: We used the archives of all the neurological wards of the Padova district to identify all subjects with a discharge diagnosis of ALS or motor neuron disease and resident in the Padova district. Results: We ascertained 182 patients (85 males and 97 females; male:female ratio 0.88:1) over the 14-year study period. The annual incidence rates adjusted by sex and age increased from 1.31/100000/year in the years 1992–1994 to 1.92/100000/year in the years 2004–2005. Conclusions: This study confirmed an ALS incidence increase over the last 25 years in the Padova district. The increase in incidence may be partially explained by the ageing of the general population rather than by an improved diagnostic assessment. [ABSTRACT FROM AUTHOR]

The off-label use of drugs is very common in cancer treatment for many reasons. This practice is challenging for pharmacists who practice in oncology, for bureaucratic and medico-legal reasons and for reasons concerning ethics. Several Italian legislative Acts and Laws allow pharmacists to have a voice in the management of off-label use of drugs in oncology and offer instruments to allow reasoning from an ethical perspective. The main aim of this paper was to identify the role of pharmacists within the ethical context in the off-label use of drugs in oncology, taking into account the legislative framework and clinical oncology setting. We consider the existing norms to develop an ethical perspective, through the values underlying the Laws and Acts. From a hermeneutical perspective, we focus on the actual oncology setting to identify the ethical space. The off-label use of drugs in Italy is currently regulated by Law 648/96, Law 94/98 and Decree Law on the therapeutic use of drugs under clinical investigation. From the oncology pharmacist’s perspective, the application of the Laws mentioned is often problematic. The disease itself brings forth many ethical issues. In particular, human experience is extremely important in oncology and cannot be separated from other considerations. When faced with the common choice of oncologists to use drugs off-label the late stages of the disease or after many chemotherapy attempts, pharmacists have to take responsibility for the sick person. This usually involves collaboration with the physician, within a process oriented by the ‘circumstances of compromise in ethics’. The pharmacist practising in oncology should promote real collaboration especially with the physician for the benefit of the sick person. The pharmacist has to maintain his/her professional integrity, and orient it towards accurate evaluation of the so-called ‘circumstances of compromise in ethics’. [ABSTRACT FROM AUTHOR]

Background: In response to limited resources, health care systems have adopted diverse costcontainment strategies and give priority to differing types of interventions. The perception of physicians, who witness the effects of these strategies, may provide useful insights regarding the impact of system-wide priority setting on access to care. Methods: We conducted a cross-sectional survey to ascertain generalist physicians' perspectives on resources allocation and its consequences in Norway, Switzerland, Italy and the UK. Results: Survey respondents (N = 656, response rate 43%) ranged in age from 28-82, and averaged 25 years in practice. Most respondents (87.7%) perceived some resources as scarce, with the most restrictive being: access to nursing home, mental health services, referral to a specialist, and rehabilitation for stroke. Respondents attributed adverse outcomes to scarcity, and some respondents had encountered severe adverse events such as death or permanent disability. Despite universal coverage, 45.6% of respondents reported instances of underinsurance. Most respondents (78.7%) also reported some patient groups as more likely than others to be denied beneficial care on the basis of cost. Almost all respondents (97.3%) found at least one cost-containment policy acceptable. The types of policies preferred suggest that respondents are willing to participate in cost-containment, and do not want to be guided by administrative rules (11.2%) or restrictions on hospital beds (10.7%). Conclusion: Physician reports can provide an indication of how organizational factors may affect availability and equity of health care services. Physicians are willing to participate in costcontainment decisions, rather than be guided by administrative rules. Tools should be developed to enable physicians, who are in a unique position to observe unequal access or discrimination in their health care environment, to address these issues in a more targeted way. [ABSTRACT FROM AUTHOR]

The article discusses the 4th annual "Conferenza Organizzativa degli Archivi delle Università Italiane," which took place on October 24-25, 2002 in Padua, Italy. Giovanni Marchesini, Rector of the University of Padua gave the opening remarks and spoke on the topic of the university's archival system. The event was split into several sessions and included topics such as the current state of archival systems, the exploitation and protection of archival materials, and excellence in archival storage.

Quantitative estimates of vector populations and their infectivity in the wild and in cultivated compartments of agroecosystems have been carried out to elucidate the role of the wild compartment in the epidemiology of Flavescence dorée (FD). Seven sites were selected for the investigations in the Piedmont Region of Italy. They were characterized by a high variety of agricultural and ecological landscape features, and included a vineyard surrounded by wild vegetation. In order to describe abundance and prevalence of FD-infected vectors in the cultivated and wild compartments of the vineyard agroecosystem, adults of Scaphoideus titanus were collected by yellow sticky traps inside and outside the vineyard over the period July 10th–September 9th, 2015. They were counted and singly analyzed for the presence of FD phytoplasmas by PCR. Multifactorial correlations among vector population level, prevalence of infected insects inside and outside the vineyards, disease prevalence in cultivated and wild Vitis plants, and location of wild Vitis plants with respect to the vineyard were analyzed. Abundance of S. titanus adults significantly decreased from the end of July onwards, particularly inside the vineyard (average range 22.7 ± 2.5 insects/trap). Percentage of FD-positive S. titanus was significantly higher outside the vineyard (up to 48% on average) compared to inside the vineyard (up to 34% on average), and increased during the season in both compartments. [ABSTRACT FROM AUTHOR]

An abstract of the study "Observational Study on the Professional Culture of Nurses and Doctors Regarding End-of-Life Situations (EOL) in some Resuscitation and ICUs in Italy," by Flavia Pegoraro et al is presented.

Abstract: Background: Acute respiratory failure (ARF) is a common event in the advanced stage of amyotrophic lateral sclerosis (ALS) and may be rarely a presenting symptom. Frequently, such patients require intubation and mechanical ventilation (MV) and, in a large proportion, receive tracheostomy, as a consequence of weaning failure. In our study, we investigated postdischarge survival and quality of life (QoL) after tracheostomy for ARF in patients with ALS. Methods: Design: This study is a retrospective chart review combined with prospective evaluation of QoL and degree of depression. Setting: The study was conducted in an adult, respiratory intensive care unit in a university hospital. Patients: Amyotrophic lateral sclerosis patients with tracheostomy for ARF between January 1, 1995 and April 30, 2008 were investigated. Intervention and measurements: (a) A retrospective chart review was used and (b) prospective administration of the 11-item short-form Life Satisfaction Index (LSI-11) and Beck Depression Inventory (BDI) questionnaires to survivors, at least 1 month after discharge from hospital, was performed. Results: Sixty patients were studied retrospectively. None of the patients died in the hospital after tracheostomy. Forty-two patients (70%) were discharged completely MV dependent, and 17 patients (28.3%) were partially MV dependent. One patient (1.6%) was liberated from MV. The median survival after tracheostomy was 21 months (range, 0-155 months). The survival rate was 65% by 1 year and 45% by 2 years after tracheostomy. Survival was significantly shorter in patients older than 60 years at tracheostomy, with a hazard ratio of dying of 2.1 (95% confidence interval, 1.1-3.9). All 13 survivors completed the LSI-11 and BDI. The mean (SD) cumulative score on the LSI-11 was 9.3 (3.6; range, 0-22; higher values indicating better QoL), similar to that obtained from a control group consisting of individuals with ALS who had not received tracheostomy (9.3 ± 4.3) and to that reported for persons in the general population. Only 15% of the tracheostomized patients (2/13) were severely depressed, according to BDI; 11 of 13 patients reported a positive view of tracheostomy and said that they would want to undergo this procedure if they could make the decision again. Conclusions: Patients with ALS have a high chance of long-term survival after tracheostomy for ARF. Although administered at the time of a respiratory crisis without being discussed in advance, tracheostomy shows good acceptance and results in acceptable QoL. [Copyright &y& Elsevier]

Myasthenia gravis (MG) is a rare, autoimmune, neurological disorder. Most MG patients have autoantibodies against acetylcholine receptors (AChRs). Some have autoantibodies against muscle-specific tyrosine kinase (MuSK) or lipoprotein-receptor-related protein 4 (LRP4), and some are seronegative. Standard of care, which includes anti-cholinesterase drugs, thymectomy, corticosteroids (CS), and off-label use of non-steroidal immunosuppressive drugs (NSISTs), is bounded by potential side effects and limited efficacy in refractory generalized MG (gMG) patients. This highlights the need for new therapeutic approaches for MG. Eculizumab, a monoclonal antibody that inhibits the complement system, has been recently approved in Italy for refractory gMG. A panel of 11 experts met to discuss unmet therapeutic needs in the acute and chronic phases of the disease, as well as the standard of care for refractory patients. Survival was emphasized as an acute phase outcome. In the chronic phase, persistent remission and early recognition of exacerbations to prevent myasthenic crisis and respiratory failure were considered crucial. Refractory patients require treatments with fast onset of action, improved tolerability, and the ability to slow disease progression and increase life expectancy. The Panel agreed that eculizumab would presumably meet the therapeutic needs of many refractory gMG patients. The panel concluded that the unmet needs of current standard of care treatments for gMG are significant. Evaluating new therapeutic options accurately is essential to find the best balance between efficacy and tolerability for each patient. Collecting real-world data on novel molecules in routine clinical practice is necessary to address unmet needs. [ABSTRACT FROM AUTHOR]

Abstract: Mutations in POMT1 and POMT2 genes were originally identified in Walker–Warburg syndrome (WWS) and subsequently reported in patients with milder phenotypes characterised by mental retardation with or without brain abnormalities and without ocular malformations. As part of a multicentric Italian study we screened the POMT1 and POMT2 genes in 61 congenital muscular dystrophy (CMD) patients with α-dystroglycan reduction on muscle biopsy and/or clinical and radiological findings suggestive of the known forms of CMD with α-dystroglycan deficiency. The aim of the study was to establish how frequently mutations in POMT1 and POMT2 occur in CMD patients in the Italian population and to evaluate the spectrum of associated phenotypes. Thirteen patients showed mutations in POMT1 and five harboured mutations in POMT2, accounting for a total of 20 different mutations, eight of which were novel (two in POMT1 and six in POMT2). Normal brain MRI associated with mental retardation and microcephaly was the most frequent finding in patients with mutations in POMT1 (six out of 13), but was also found in a patient with POMT2 mutations. Predominant cerebellar hypoplasia was also frequent both in patients with POMT1 (three out of 13) and POMT2 (three out of 5) mutations. A MEB phenotype with frontal cortical dysplasia and pons abnormalities was found in two patients with POMT1 and in one with POMT2 mutations, while a WWS phenotype was only found in a case with mutations in POMT1. Mutations causing frameshifts and stop codons were responsible for the more severe phenotypes. Our results provide further evidence that, as previously reported for FKRP, the array of mutations in POMT1 and POMT2 is ample and the spectrum of associated phenotypes is wider than initially thought. [Copyright &y& Elsevier]

In dysferlinopathy patients, the upper limb muscles are affected in the later stages of the disease, and muscle fat replacement of arm and forearm muscles follows thigh and leg involvement. Additionally, increased disease activity (such as inflammation) in lower limb muscles has been reported to be a feature in patients with dysferlinopathy. Adding to the COS1 results, a longitudinal quantitative MRI study in upper limbs was set up in four clinical centers (UK, France, Italy, USA), investigating both muscle fat fraction (FF; reflecting the extent of muscle fat replacement) and water T2 (reflecting the extent of muscle inflammation). The MRI data presented here were acquired in two of the four sites, at baseline, 6-months, and/or 12-months. The MRI acquisitions included FF and water T2 mapping at the level of the upper arm (deltoid, triceps and biceps brachialis) and forearm (extensor, flexor). Student's t-tests were performed (P<0.05). Patients in this cohort (17 female, 10 male, 89% ambulant, 70% LGMD R2 diagnosis) were 46.1±12.1 years old and had symptoms for 14.9±7.7 years. At baseline, the lowest FF values were found in forearm muscles (23.5±14.6% in flexor, 24.1±16.1% in extensor). FF values in upper arm muscles were 30.1±18.6%, 31.1±21.4% and 35.1±24.1% in deltoid, biceps brachialis and triceps muscles, respectively. Per 6 months, FF increased, on average, by 2 to 3% in forearm muscles and 2 to 5% in upper arm muscles (P>0.05). Biceps brachialis and extensor muscles showed normal water T2 values (<37.0 ms), whereas elevated water T2 values were found in flexor and triceps muscles (≥38.7 ms) across the three visits. These quantitative MRI data showed that the upper arm muscles were somewhat more involved than forearm muscles. A high inter-patient heterogeneity of disease progression was observed, resulting in non-significant results for changes in FF. The persistent disease activity in some muscles (reflected by elevated water T2 values across the entire study) was earlier shown in thigh and leg muscles in dysferlinopathy. [ABSTRACT FROM AUTHOR]

Despite all the advances in diagnosis and management of Duchenne muscular dystrophy over the past 50 years, the average age at diagnosis in most countries in the world around is still around 4–5 years. This retrospective study investigates the age at diagnosis in Italy in the past 10 years. We report findings from 384 boys who were diagnosed with DMD from 2005 to 2014. The mean age at first medical contact, which raised the suspicion of DMD, was 31 months. The mean age at diagnosis was 41 months. The finding that more frequently brought to suspect a DMD was the incidental finding of consistent elevated creatine kinase serum level detected during routine assessments in children undergoing general anesthesia or with intercurrent illness. This was followed by motor delay and signs of muscle weakness. Initial concerns were raised by general pediatricians (29%), specialists at tertiary centers (35%) or first level hospitals (23%). In children presenting incidental elevated creatine kinase values the diagnosis was achieved earlier than in children presenting a developmental delay. The mean age at diagnosis in our cohort was about 10–12 months lower than that reported in other countries. [ABSTRACT FROM AUTHOR]

Limb girdle muscular dystrophies (LGMD) are genetic heterogeneous disorders characterized by slow but progressive muscular impairment. Despite the recent identification of new genes, about 30% of these LGMDs remain without molecular diagnosis. However clinical-genetic correlations are fundamental for genetic counselling, definition of natural history and insight into pathogenesis. We collected detailed clinical, biochemical, histological and molecular data of 467 Italian LGMD patients, belonging to 8 neuromuscular Italian centres. Detailed data about neuromuscular, cardiological, respiratory involvement as far as molecular analysis and muscle biopsy were collected. Molecular analysis identified mutations in LGMD causative genes in 312 patients; 109 patients (23.1%) are still without a molecular diagnosis and 46 subjects (9.8%) carried heterozygous mutations in genes responsible for autosomal recessive forms. The relative frequency was as follows: 5.8% LGMD1B, 11.2% LGMD1C, 24.3% LGMD2A, 25.6% LGMD2B, 9.6% LGMD2I, 9.9% LGMD2D, 6.4% LGMD2E, 4.2% LGMD2C, 1.9% LGMD2L, 0.3% LGMD2F. Interestingly 1 LGMD patient (0.3%) carried mutations in ISPD and one patient in LAMA2 gene. Onset spans from the first decade to adulthood; LGMD2E being the most precocious (6.2 ± 5.3 years) and LGMD2L the latest (36.6 ± 7.1 years). Creatine-kinase values were generally increased, especially in sarcoglycanopathies, LGMD2B, LGMD1C. Cardiomyopathy was more frequent in LGMD1B (100%), LGMD2E (47%) and LGMD2I (50%) and restrictive pulmonary involvement in LGMD2I (53%) and LGMD2E (47%). About 30% of patients were wheelchair bound. The study of undiagnosed patients will potentially lead to identification of new LGMD causative genes. Overall this study defined the relative frequency of Italian LGMD and improved the knowledge about clinical, morphological and molecular spectrum as far as their natural history as far as the parameters that can better define the clinical evolution of these forms. [ABSTRACT FROM AUTHOR]

Abstract: Amyotrophic lateral sclerosis (ALS) is as an adult-onset neurodegenerative disorder involving both upper and lower motor neurons. About 5% of all cases exhibit signs of frontotemporal degeneration (FTD). We established the mutation frequency of C9ORF72, SOD1, TARDBP, and FUS genes in 307 patients with sporadic ALS, 46 patients with familial ALS (FALS), and 73 patients affected with FTD, all originating from the northeastern part of Italy. C9ORF72 pathogenic expansion was found on 22% of familial ALS, 5% of sporadic ALS, and 14% of FTD patients, resulting the most frequently genetic determinant in our cohort. Sequence analysis of ALS cohort identified 2 novel variants on SOD1 (p.Glu41Gly) and FUS (p.Gly496Glyfs*31). Interestingly, the single base deletion on FUS was observed in an homozygous state, suggesting a recessive pattern of inheritance. No point mutations were identified on FTD cohort. Although useful to direct genetic testing, this study results expand the current knowledge of ALS genetics. [Copyright &y& Elsevier]

Objective: To describe the hematologic outcome and long-term survival of patients enrolled in the Shwachman-Diamond syndrome Italian Registry., Study Design: A retrospective and prospective study of patients recorded in the Shwachman-Diamond syndrome Italian Registry., Results: The study population included 121 patients, 69 males and 52 females, diagnosed between 1999 and 2018. All patients had the clinical diagnosis confirmed by mutational analysis on the SBDS gene. During the study period, the incidence of SDS was 1 in 153 000 births. The median age of patients with SDS at diagnosis was 1.3 years (range, 0-35.6 years). At the first hematologic assessment, severe neutropenia was present in 25.8%, thrombocytopenia in 25.5%, and anemia in 4.6% of patients. A normal karyotype was found in 40 of 79 patients, assessed whereas the most frequent cytogenetic abnormalities were isochromosome 7 and interstitial deletion of the long arm of chromosome 20. The cumulative incidence of severe neutropenia, thrombocytopenia, and anemia at 30 years of age were 59.9%, 66.8%, and 20.2%, respectively. The 20-year cumulative incidence of myelodysplastic syndrome/leukemia and of bone marrow failure/severe cytopenia was 9.8% and 9.9%, respectively. Fifteen of 121 patients (12.4%) underwent allogeneic stem cell transplantation. Fifteen patients (12.4%) died; the probability of overall survival at 10 and 20 years was 95.7% and 87.4%, respectively., Conclusions: Despite an improvement in survival, hematologic complications still cause death in patients with SDS. Further studies are needed to optimize type and modality of hematopoietic stem cell transplantation and to assess the long-term outcome in nontransplanted patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)