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Accumulating evidence indicates that cerebral desaturation in the perioperative period occurs more frequently than recognized. Combining monitoring modalities that reflect different aspects of cerebral perfusion status, such as near-infrared spectroscopy, jugular bulb saturation, and transcranial Doppler ultrasonography, may provide an extended window for prevention, early detection, and prompt intervention in ongoing hypoxic/ischemic neuronal injury and, thereby, improve neurologic outcome. Such an approach would minimize the impact of limitations of each monitoring modality, while individual components complement each other, enhancing the accuracy of acquired information. Current literature has failed to demonstrate any clear-cut clinical benefit of these modalities on outcome prognosis.

Background and objective Bone fragility has been linked to COVID-19 severity. The objective of this study was to evaluate whether a diagnosis of vertebral fracture (VF) increased mortality risk in COVID-19 patients and whether this effect was greater than in those without COVID-19. Methods We assessed VFs by computed tomography (CT) in a cohort of 501 patients consecutively admitted to the emergency department (ED) for clinical suspicion of SARS-CoV-2 infection during the first wave of pandemic emergency. Of those, 239 had a confirmed diagnosis of COVID-19. Results VF prevalence was similar between COVID-19 and non-COVID-19 groups (22.2 vs. 19%; p = 0.458). Death rates were similar between COVID-19 and non-COVID-19 groups at both 30 (15.8 vs. 12.2%; p = 0.234) and 120 days (21.8 vs. 17.6%; p = 0.236). The mortality risk was higher in COVID-19 patients either with one or multiple fractures compared to those without VFs, at 30 and 120 days, but statistical significance was reached only in those with multiple VFs (30-day HR 3.03, 95% CI 1.36–6.75; 120-day HR 2.91, 95% CI 1.43–5.91). In the non-COVID-19 group, the 30-day mortality risk was significantly higher in patients either with one (HR 7.46, 95% CI 3.12–17.8) or multiple fractures (HR 6.2, 95% CI 2.75–13.98) compared to those without VFs. A similar effect was observed at 120 days. After adjustment for age, sex and bone density, mortality risk remained associated with VFs in the non-COVID-19 group only. Conclusions VFs were not independently associated with short-term mortality in patients with COVID-19, but they strongly increased mortality risk in those without COVID-19.

Dear Editor, Generalized granuloma annulare (GGA) is a granulomatous necrobiotic inflammatory condition characterized by widespread annular lesions involving trunk and limbs with variable disease course and frequently associated with endocrinological, neoplastic, and infectious diseases. Patho-mechanism is likely based on T-helper-1 cytokines and often the course is persistent despite several empirical therapies. Apremilast is an oral phosphodiesterase-4 (PDE-4) inhibitor approved by EMA for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis. Recently few cases of GGA treated with this small molecule were reported considering its ability to reduce the T-helper-1 cytokines.

We present a 53‐year‐old male with nonketotic hyperglycinemia (NKH) who presented in decompensated state to our university hospital several months prior to a primary diagnosis of multifocal pneumonia accompanied by reports of seizure‐like activity, altered mental status, tremors, and fever. He was initially diagnosed with NKH in his preschool years, over 40 years previously, along with his younger sister. At that time, he had developmental and physical delays (which his sister also experienced). His health course has been relatively uneventful otherwise, as regards decompensation of his disease, and he has not been on the standard regimens of reduced dietary glycine intake along with dextromethorphan and sodium benzoate. Recent molecular confirmation of NKH was completed and both he and his sibling likely have an attenuated form of NKH mediated by the combined effects of their variants. This paper presents what we believe to be report of the oldest surviving individuals with attenuated NKH.

Transnasal transsphenoidal (TNTS) pituitary surgery is associated with short-lived but intense nociceptive stimuli which cause substantial hemodynamic perturbations that may increase blood loss and impair visualization of the surgical field. This systematic review aimed to critically appraise the clinical evidence for the efficacy and safety of various anesthetic techniques, other pharmacological modalities, and supplementary interventions by assessing intraoperative systemic hemodynamics, use of adjunct medications, quality of the surgical field, intraoperative blood loss, and recovery profiles in patients undergoing TNTS pituitary surgery. Relevant randomized clinical trials and observational studies were identified in a systematic literature search; 16 studies (13 randomized clinical trials, 3 observational studies) enrolling a total of 907 patients were identified for inclusion in this review. Propofol provided more potent hemodynamic control compared with volatile anesthetics with a sparing effect on the need for additional drugs to blunt hemodynamic responses. Recovery profiles between propofol and sevoflurane were either equivalent or favored sevoflurane, but both agents were superior to isoflurane. Regarding intraoperative analgesia, remifentanil was associated with superior hemodynamic control and recovery profiles than fentanyl. Dexmedetomidine had beneficial effects on hemodynamics, surgical field quality, recovery characteristics, and nociceptive properties compared with placebo. Although there was no clear-cut superiority of other adjunct pharmacological modalities on hemodynamic responses during surgery, regional blocks were associated with beneficial impacts on both primary and secondary outcomes. In summary, short-acting anesthetics, analgesics and dexmedetomidine seem to improve intraoperative hemodynamics, blood loss, and recovery qualities during TNTS pituitary surgery. However, definitive conclusions cannot be drawn because of methodological heterogeneity in the identified studies.

More than 60 SARS-CoV-2 vaccine candidates are currently in clinical trials and more than 170 vaccines are in different stages of preclinical evaluation worldwide

Nickel is the most common cause of contact allergy in the general population and the most frequently detected allergen in patients patch tested for suspected allergic contact dermatitis (ACD). ACD from nickel is a typical type IV hypersensitivity. Nickel allergy is mostly caused by nonoccupational exposure, such as jewelry and clothing decorations, metal tools, medical devices (mainly orthopedic and orthodontic implants, cardiovascular prosthesis), eyeglasses, utensils, keys, pigment for paint, cosmetics, and food (mainly legumes, chocolate, salmon, peanuts). Occupational exposure can involve several workers (mechanics, metalworkers, platers, hairdressers, jewelers, workers in the constructions and electronic industries), classically involving hands and forearms. The classic clinical pattern of ACD caused by nickel is characterized by eczematous dermatitis involving the sites of direct contact with the metal. Non-eczematous-patterns are reported, including lichenoid dermatitis, granuloma annulare, vitiligo-like lesions, dyshidrosiform dermatitis, and vasculitis. In the case of systemic exposure to nickel, sensitized patients could develop systemic contact dermatitis. Patch testing represents the gold standard for the diagnosis of ACD from nickel. Treatment includes avoidance of contact with products containing nickel and the patient’s education about the possible use of alternative products. A recent EU nickel directive, regulating the content and release of nickel from products, has caused a decrease of nickel contact allergy in some European countries. Nickel allergy is a relevant issue of public health with significant personal, social, and economic impact. This review summarizes epidemiology, pathomechanism, clinical patterns, treatment, and prevention programs.

Epidemiological evidence shows clear gender disparities in the Coronavirus 2019 Disease (COVID-19) severity and fatality. This may reflect the contribution of gender-related factors, such as sex hormones, to COVID-19 pathogenesis. However, the mechanism linking gender disparities to COVID-19 severity is still poorly understood. In this review, we will pinpoint several elements involved in COVID-19 pathogenesis that are regulated by the two main sex hormones, estrogen and androgen. These include tissue specific gene regulation of SARS-CoV2 entry factors, innate and adaptive immune responses to infection, immunometabolism, and susceptibility to tissue injury by cytopathic effect or hyper-inflammatory response. We will discuss the mechanistic link between sex hormone regulation of COVID-19 pathogenetic factors and disease severity. Finally, we will summarize current evidence from clinical studies and trials targeting sex hormones and their signalling in COVID-19. A better understanding of the role of sex hormones in COVID-19 may identify targets for therapeutic intervention and allow optimization of treatment outcomes towards gender-based personalised medicine.

Background Current guidelines suggest to consider dual antiplatelet therapy (DAPT) continuation for longer than 12 months in selected patients with myocardial infarction (MI). Hypothesis We sought to assess the criteria used by cardiologists in daily practice to select patients with a history of MI eligible for DAPT continuation beyond 1 year. Methods We analyzed data from the EYESHOT Post-MI, a prospective, observational, nationwide study aimed to evaluate the management of patients presenting to cardiologists 1 to 3 years from the last MI event. Results Out of the 1633 post-MI patients enrolled in the study between March and December 2017, 557 (34.1%) were on DAPT at the time of enrolment, and 450 (27.6%) were prescribed DAPT after cardiologist assessment. At multivariate analyses, a percutaneous coronary intervention (PCI) with multiple stents and the presence of peripheral artery disease (PAD) resulted as independent predictors of DAPT continuation, while atrial fibrillation was the only independent predictor of DAPT interruption for patients both at the second and the third year from MI at enrolment and the time of discharge/end of the visit. Conclusions Risk scores recommended by current guidelines for guiding decisions on DAPT duration are underused and misused in clinical practice. A PCI with multiple stents and a history of PAD resulted as the clinical variables more frequently associated with DAPT continuation beyond 1 year from the index MI.

Background and aim: Over 80% (365/454) of the nation’s centers participated in the Italian Society of Nephrology COVID-19 Survey. Out of 60,441 surveyed patients, 1368 were infected as of April 23rd, 2020. However, center-specific proportions showed substantial heterogeneity. We therefore undertook new analyses to identify explanatory factors, contextual effects, and decision rules for infection containment. Methods: We investigated fixed factors and contextual effects by multilevel modeling. Classification and Regression Tree (CART) analysis was used to develop decision rules. Results: Increased positivity among hemodialysis patients was predicted by center location [incidence rate ratio (IRR) 1.34, 95% confidence interval (CI) 1.20–1.51], positive healthcare workers (IRR 1.09, 95% CI 1.02–1.17), test-all policy (IRR 5.94, 95% CI 3.36–10.45), and infected proportion in the general population (IRR 1.002, 95% CI 1.001–1.003) (all p < 0.01). Conversely, lockdown duration exerted a protective effect (IRR 0.95, 95% CI 0.94–0.98) (p < 0.01). The province-contextual effects accounted for 10% of the total variability. Predictive factors for peritoneal dialysis and transplant cases were center location and infected proportion in the general population. Using recursive partitioning, we identified decision thresholds at general population incidence ≥ 229 per 100,000 and at ≥ 3 positive healthcare workers. Conclusions: Beyond fixed risk factors, shared with the general population, the increased and heterogeneous proportion of positive patients is related to the center’s testing policy, the number of positive patients and healthcare workers, and to contextual effects at the province level. Nephrology centers may adopt simple decision rules to strengthen containment measures timely.

Bone fragility is one of the possible complications of diabetes, either type 1 (T1D) or type 2 (T2D). Bone fragility can affect patients of different age and with different disease severity depending on type of diabetes, disease duration and the presence of other complications. Fracture risk assessment should be started at different stages in the natural history of the disease depending on the type of diabetes and other risk factors. The risk of fracture in T1D is higher than in T2D, imposing a much earlier screening and therapeutic intervention that should also take into account a patient's life expectancy, diabetes complications etc. The therapeutic armamentarium for T2D has been enriched with drugs that may influence bone metabolism, and clinicians should be aware of these effects.Considering the complexity of diabetes and osteoporosis and the range of variables that influ-ence treatment choices in a given individual, the Working Group on bone fragility in patients with diabetes mellitus has identified and issued recommendations based on the variables that should guide screening of bone fragility and management of diabetes and bone fragility: (A) ge, (B)MD, (C)omplications, (D)uration of disease, & (F)ractures (ABCD&F). Consideration of these parameters may help clinicians identify the best time for screening, the appropriate glycaemic target and anti-osteoporosis drug for patients with diabetes at risk of or with bone fragility.(c)& nbsp;2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

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Objective Non-melanoma skin cancer (NMSC) has been rapidly increasing in incidence over the past 30 years. Mainstays of treatment remain surgery and radiotherapy, particularly in older and/or frail patients (≥75 years old) that often require a personalized treatment strategy using innovative biotechnologies. High-dose-rate interventional radiotherapy (HDR-IRT) seems to be an excellent option for NMSC. Material and Methods Nineteen aged patients with advanced, biopsy proven NMSC were treated with exclusively HDR-IRT. A personalized double-layer mould of thermoplastic mask material was applied to the skin surface. Plastic tubes were fixed on the mould in appropriate geometry over the target area. Planning computed tomography (CT) images were acquired with 2.5 mm slice thickness and transmitted to the planning system. Treatment intention was to deliver ≥95% of the prescribed dose to the Planning Target Volume (PTV), accepting 90% as satisfactory. Toxicities were assessed using the Common Terminology Criteria for Adverse Events scale (CTCAE) v. 4.0. Results Median age was 86 years. Acute toxicity: Grade 2 erythema appeared in all 19 patients. Towards the end of each treatment schedule, epidermolysis developed which was resolved within 6 weeks of completing HDR-IRT. Late toxicity: Grade 1 skin atrophy, pigmentation changes and alopecia in field were observed in all patients. At last follow-up, all patients were disease free. Conclusions Personalized HDR-IRT appears to be safe and effective for frail older patients and a valid alternative to supportive care for those with contraindication to surgery. Future investigations using also large database analysis seem to be advisory.

Increased circulating sclerostin levels and accumulation of advanced glycation end-products (AGEs) are two potential mechanisms underlying low bone turnover and increased fracture risk in type 2 diabetes (T2D). Recent data from our group have shown that T2D affects the expression of genes controlling bone formation (SOST and RUNX2) and that accumulation of AGEs is associated with impaired bone microarchitecture. Whether the expression of the Wnt beta-catenin target genes is altered in T2D, and whether AGEs accumulation it is associated with type 1 Collagen (COL1A1) alteration is still unknown. We hypothesized that increased SOST gene expression leads to downregulation of Wnt β- catenin target genes (TCF/LEF1) and AGEs accumulation is related to a downregulation of COL1A1 in bones from subjects with T2D. We analyzed bone tissue from femoral heads of 14 T2D postmenopausal women (mean HbA1c 6.5%) and 21 age- and BMI-comparable nondiabetic women undergoing hip replacement surgery. We found that TCF-LEF1 was significantly lower in T2D compared to non- diabetic subjects (p=0.0092). Dickkopf -1 (DKK-1), the other inhibitor of beta-catenin-dependent Wnt signalling besides sclerostin, was not different between groups (p=0.1083). However, analysis of correlation showed that DKK-1 increases with age (r2=0.038; p=0.043) and HbA1c (r2=0.503; p=0.048) in T2D subjects. COL1A1 gene expression was lower in T2D compared to controls although significance was not fully reached (p=0.0564). Importantly, AGEs bone content was significantly higher in T2D compared to nondiabetics (1.5 fold increase; p In conclusion, our data show that even in patients with relatively good glycemic control, T2D affects the expression of collagen and Wnt beta-catenin target genes. We also found that accumulation of AGEs is possibly associated with alteration in collagen gene expression. We provide novel insights that may help understand the mechanisms underlying bone fragility in T2D. Disclosure G. Leanza: None. F. Tramontana: None. F. Cannata: None. A. Piccoli: None. M. Faraj: None. V. Viola: None. R. Strollo: None. N. Napoli: None. P. Pozzilli: None. Funding Campus Bio-Medico University

Background Budesonide was included in the European Baseline Series in 2000 as the most suitable marker forcorticosteroid hypersensitivity. In the last two decades, a decreasing trend of budesonide allergy has been observed. Objectives To estimate the prevalence of positive patch test reactions to budesonide in a large, Italian patch test population, characterizing patients according to MOAHLFA index and evaluating the benefit with extended readings of budesonide patch test. Methods Retrospective analysis of patient demographics and patch test results over a 2-year period (2018-2019) was performed at 14 patch test clinics in Italy. Results Ninety out of 14 544 (0.6%) patients reacted to budesonide 0.01% pet.. Positive reactions were mild in 54.4% and late readings at day 7 showed new positive reactions in 37.8% of patients. The MOAHLFA index showed a significant positive association with male gender, atopic dermatitis, and age >40 years and a significant negative association with hand and face dermatitis. Conclusions We documented a low prevalence of budesonide allergy in Italy, confirming its decreasing trend recently reported in the literature. Nevertheless, budesonide needs to be maintained in the baseline series for its good ability to detect corticosteroid sensitization.

Adverse drug reactions (ADRs) are common and influence negatively the patient's therapeutic options. They recognize multiple pathogenic mechanisms, some of immunological origin, and the clinical manifestations involve several organs and systems, including skin and/or mucous membranes in 25-30% of patients. The identification of the trigger drug remains a medical challenge, mainly in poly-medicated patients. Anamnesis and clinical approach are crucial, but allergy work-up is the essential tool to confirm or exclude the causative role of the culprit drug. Besides in-vitro tests and drug provocation test, skin tests (ST) represent the cornerstone: patch test in delayed ADR, prick test in immediate ADR, and intradermal test in both. Nevertheless, ST are in continuous evolution and characterized by technical difficulties (concentration and vehicle) that can influence their value and specificity. In this article we review the indications and the rules in performing patch test, prick test, and intradermal test with the most commonly used drugs in Italy to determine the cause of a cutaneous and/or mucous ADR, precise the involved pathogenic mechanism, and provide a valid therapeutic alternative to the patient.

Atopic dermatitis (AD) therapeutic approach calls for a long-term treatment. Treatment options for AD have recently undergone a revolutionary change by the introduction of the first biologic drug. Availability in daily practice of the last version of international AD guidelines, taking peculiarities of the country into account, can contribute to good clinical practice in Italy. To adapt European Dermatology Forum (EDF) guidelines for AD to the Italian medical–legal context, the EDF guidelines were assessed independently by two independent Italian renowned experts in the field and further integrated with articles published and systematically reviewed before May 2019. The first draft was collegially corrected and updated by the members of the SIDEMAST, ADOI, and SIDAPA. Recommendation levels (A; B; C; D) were graded based on the evidence levels (1–4). The adapted guidelines presented here focus on topical and systemic therapies in AD patients, both children and adults. As opposed to previous Italian guidelines, they include indications about biologics. New relevant evidence available from very recent literature and peculiarities of the Italian medical and legal context have been integrated in the revision process. If compared to general guidelines for AD not adapted to a specific national and cultural context, a revision for specific Italian needs is now available: It comprises the option of implementing the new biologic treatments and is likely to provide an important contribution to the improvement of clinical practice in Italy. Cooperation between patients, dermatologists, allergologists, and pediatricians remains mandatory in AD management. The authors of the present revision recommend an update of the Italian guidelines to be performed at least every second year.

Inflammatory bowel diseases (IBDs) may be associated with extra-intestinal manifestations. Among these, mucocutaneous manifestations are relatively frequent, often difficult to diagnose and treat, and may complicate the course of the underlying disease. In the present review, a summary of the most relevant literature on the dermatologic manifestations occurring in patients with inflammatory bowel diseases has been reviewed. The following dermatological manifestations associated with IBDs have been identified: (i) specific manifestations with the same histological features of the underlying IBD (occurring only in Crohn’s disease); (ii) cutaneous disorders associated with IBDs (such as aphthous stomatitis, erythema nodosum, psoriasis, epidermolysis bullosa acquisita); (iii) reactive mucocutaneous manifestations of IBDs (such as pyoderma gangrenosum, Sweet’s syndrome, bowel-associated dermatosis-arthritis syndrome, aseptic abscess ulcers, pyodermatitis–pyostomatitis vegetans, etc.); (iv) mucocutaneous conditions secondary to treatment (including injection site reactions, infusion reactions, paradoxical reactions, eczematous and psoriasis-like reactions, cutaneous infections, and cutaneous malignancies); (v) manifestations due to nutritional malabsorption (such as stomatitis, glossitis, angular cheilitis, pellagra, scurvy, purpura, acrodermatitis enteropathica, phrynoderma, seborrheic-type dermatitis, hair and nail abnormalities). An accurate dermatological examination is essential in all IBD patients, especially in candidates to biologic therapies, in whom drug-induced cutaneous reactions may assume marked clinical relevance.

A growing body of evidence suggests a potential link between bone metabolism and cardiovascular disease. Aim of this study was to investigate the relationship between levels of circulating bone turnover biomarkers and advanced atherosclerosis. Klotho (KL), sclerostin (SOST), osteopontin (OPN) and osteoprotegerin (OPG) were measured in patients undergoing elective coronary angiography and carotid Doppler ultrasound. The primary outcome was the difference in bone biomarkers levels between participants with and without advanced atherosclerosis, defined as the presence of a critical coronary (≥70%) and/or carotid (≥50%) stenosis. A total of 80 subjects (32.5% females) with a mean age of 68 ± 10 years were included. Advanced atherosclerosis was detected in 55 (68.8%) patients. Subjects with advanced atherosclerosis showed higher serum levels of OPG (p = 0.0015) and SOST (p = 0.017) and similar levels of KL (p = 0.62) and OPN (p = 0.06) compared to patients without. After adjustment for age and sex, only elevated levels of OPG remained significantly associated with advanced atherosclerosis (p = 0.011). Higher serum levels of OPG are independently associated with advanced atherosclerosis confirming a common bond between bone metabolism and vascular disease. Further investigations on the role of selected bone biomarkers in the pathogenesis of cardiovascular disease are needed.

From the beginning of the year 2020, the world was affected by a coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2, leading to a shortage of personal protective equipment (PPE) at a global level, and thus generating exposure of health professionals to this extremely contagious virus. Within this context, the present work seeks to present an alternative for the production of face shields “face shields,” in which it recommends its production “in house” through 3D printing, in principle initiated by Prusa Research, where we download your project of support of facial protectors, proceeding with printing through the 3D printer Gtmax3D Core H5. The authors produced a face shield in ABS, in a total time of 3 hours and 44 minutes. Thus, the model presented proved to be feasible, at a low cost, adding to the list of possibilities to produce inputs necessary to maintain the fight against this epidemic.

Coronavirus 2019 disease (COVID-19) mostly adversely affects the elderly, a population at higher risk for low serum 25-hydroxyvitamin D (25(OH)D) levels. In this viewpoint, we highlight the well-known musculoskeletal properties of vitamin D, which are particularly relevant in the context of COVID-19, suggesting further potential benefits through extra-skeletal effects. Maintaining optimal 25(OH)D is crucial to prevent falls, frailty and fractures in elderly patients, with low activity levels due to lockdown, or who are relatively immobilized during hospitalization and after discharge for prolonged periods of time. Hypovitaminosis D is also associated with susceptibility to respiratory infections, admissions to the intensive care unit, and mortality. We underscore the importance of achieving desirable serum 25(OH)D in COVID-19 elderly patients, to ensure beneficial musculoskeletal effects and possibly respiratory effects of vitamin D, in the context of COVID-19.

Background: The efficacy of increasing dietary fiber intake (DFI) to ameliorate glycemic control in patients with type 2 diabetes (T2D) is still controversial. In this randomized open-label comparator-controlled study we tested the effect of high-fiber diet and fiber supplement on glycemic control in patients with T2D on metformin monotherapy. Methods: Seventy-eight T2D overweight patients on metformin monotherapy were randomized 1:2:1 to 12 weeks intensive nutrition program to follow high-fiber diet (HFD), dietary fiber supplementation (FS) or standard diet recommendations (SDR). Dietary recommendations were reinforced in all groups every 4 weeks by study dieticians. Biochemistry, anthropometric measures, food frequency questionnaires to asses DFI were collected at baseline and after 12 weeks. Results: At baseline groups did not differ in terms of mean age, BMI, metformin intake, HbA1c, fiber and calorie intake (p>0.05 for all). After three months, DFI significantly increase in both HDF and FS group but not in SDR group (HFD: 19.8 ± 6.1 g vs. 24.3 ± 6.8 g, p= 0.0001; FS: 17.5 ± 5.9 g vs. 27.0 ± 6.2 g p< 0.0001; SDR: 22.8 ± 9.1 g vs. 21.2 ± 6.4 g, p= 0.32). HbA1c significantly improved in all groups (HFD: 7.1 ± 0.5 % vs. 6.6 ± 0.6 %, p< 0.0001; FS: 7.1 ± 0.5 % vs. 6.8 ± 0.5 % p< 0.001; SDR: 7.2 ± 0.4 % vs. 6.7 ± 0.5 g, p< 0.001). All HFD, FS and SDR intervention reduced mean body weight by 2.1 ± 2.6 Kg (p< 0.0001), 1.0 ± 1.8 Kg (p< 0.05) and 1.1 ± 2.1 Kg (p< 0.05), respectively. Changes in HbA1c and body weight did not differ among groups. A significant correlation between calorie intake and the reduction of HbA1c levels was seen across groups (r= 0.307 p Conclusions: Intensive nutrition education programs with monthly meetings similarly reduced HbA1c in all groups. Furthermore, our study suggested that rather than fiber intake, caloric restriction followed by moderate weight loss is the main driver for glycemic improvement in overweight patients with T2D. Disclosure F. Tramontana: None. E. Maddaloni: Consultant; Self; Merck KGaA. Speaker’s Bureau; Self; Abbott, AstraZeneca, Pikdare. S. Greci: None. G. Defeudis: None. R. Strollo: None. P. Pozzilli: Advisory Panel; Self; Abbott, AstraZeneca, Eli Lilly and Company. Research Support; Self; Medtronic, Sanofi. N. Napoli: None.

Parkinson disease (PD) is a chronic neurodegenerative condition that leads to progressive disability. PD-related reductions in muscle strength have been reported to be associated with lower functional performance and balance confidence with an increased risk of falls. Progressive resistance training (PRT) improves strength, balance, and functional abilities. This umbrella review examines the efficacy of PRT regarding muscular strength in PD patients. The PubMed, PEDro, Scopus, and Cochrane Library databases were searched from January 2009 to August 2019 for systematic reviews and meta-analyses conducted in English. The populations included had diagnoses of PD and consisted of males and females aged >18 years old. Outcomes measured were muscle strength and enhanced physical function. Eight papers (six systematic reviews and meta-analyses and two systematic reviews) were considered relevant for qualitative analysis. In six of the eight studies, the reported severity of PD was mild to moderate. Each study analyzed how PRT elicited positive effects on muscle strength in PD patients, suggesting 10 weeks on average of progressive resistance exercises for the upper and lower limbs two to three times per week. However, none of the studies considered the postworkout follow-up, and there was no detailed evidence about the value of PRT in preventing falls. The possibility of PRT exercises being effective for increasing muscle strength in patients with PD, but without comorbidities or severe disability, is discussed. Overall, this review suggests that PRT should be included in rehabilitation programs for PD patients, in combination with balance training for postural control and other types of exercise, in order to preserve cardiorespiratory fitness and improve endurance in daily life activities.

Importance Methicillin-resistantStaphylococcus aureus(MRSA) bacteremia is associated with mortality of more than 20%. Combining standard therapy with a β-lactam antibiotic has been associated with reduced mortality, although adequately powered randomized clinical trials of this intervention have not been conducted. Objective To determine whether combining an antistaphylococcal β-lactam with standard therapy is more effective than standard therapy alone in patients with MRSA bacteremia. Design, Setting, and Participants Open-label, randomized clinical trial conducted at 27 hospital sites in 4 countries from August 2015 to July 2018 among 352 hospitalized adults with MRSA bacteremia. Follow-up was complete on October 23, 2018. Interventions Participants were randomized to standard therapy (intravenous vancomycin or daptomycin) plus an antistaphylococcal β-lactam (intravenous flucloxacillin, cloxacillin, or cefazolin) (n = 174) or standard therapy alone (n = 178). Total duration of therapy was determined by treating clinicians and the β-lactam was administered for 7 days. Main Outcomes and Measures The primary end point was a 90-day composite of mortality, persistent bacteremia at day 5, microbiological relapse, and microbiological treatment failure. Secondary outcomes included mortality at days 14, 42, and 90; persistent bacteremia at days 2 and 5; acute kidney injury (AKI); microbiological relapse; microbiological treatment failure; and duration of intravenous antibiotics. Results The data and safety monitoring board recommended early termination of the study prior to enrollment of 440 patients because of safety. Among 352 patients randomized (mean age, 62.2 [SD, 17.7] years; 121 women [34.4%]), 345 (98%) completed the trial. The primary end point was met by 59 (35%) with combination therapy and 68 (39%) with standard therapy (absolute difference, −4.2%; 95% CI, −14.3% to 6.0%). Seven of 9 prespecified secondary end points showed no significant difference. For the combination therapy vs standard therapy groups, all-cause 90-day mortality occurred in 35 (21%) vs 28 (16%) (difference, 4.5%; 95% CI, −3.7% to 12.7%); persistent bacteremia at day 5 was observed in 19 of 166 (11%) vs 35 of 172 (20%) (difference, −8.9%; 95% CI, −16.6% to −1.2%); and, excluding patients receiving dialysis at baseline, AKI occurred in 34 of 145 (23%) vs 9 of 145 (6%) (difference, 17.2%; 95% CI, 9.3%-25.2%). Conclusions and Relevance Among patients with MRSA bacteremia, addition of an antistaphylococcal β-lactam to standard antibiotic therapy with vancomycin or daptomycin did not result in significant improvement in the primary composite end point of mortality, persistent bacteremia, relapse, or treatment failure. Early trial termination for safety concerns and the possibility that the study was underpowered to detect clinically important differences in favor of the intervention should be considered when interpreting the findings. Trial Registration ClinicalTrials.gov Identifier:NCT02365493

Patch testing is the standard procedure used to diagnose allergic contact dermatitis. It is an in-vivo test, which reproduces the reaction to a contact allergen. This in-vivo test aims to reproduce the elicitation phase of allergic contact dermatitis and is performed applying allergens under occlusion on the skin under standardized conditions. These guidelines for the best practice in performing patch test have been developed by an Italian group of experts taking in account the Italian legislation and local pharmacological governance. Guidelines are adapted from the original article under the guidance of the European Society of Contact Dermatitis (ESCD) and on the basis of the SIDAPA guidelines.

Dear Editor, A 47‐year‐old calf breeder presented with a history of four recurrences of painless erythematous, nodular–ulcerative and exudative lesions of both hands (a), suggestive of Parapoxvirus infection.

Tumours can be viewed as aberrant tissues or organs sustained by tumorigenic stem-like cells that engage into dysregulated histo/organogenetic processes. Paragangliomas, prototypical organoid tumours constituted by dysmorphic variants of the vascular and neural tissues found in normal paraganglia, provide a model to test this hypothesis. To understand the origin of paragangliomas, we built a biobank comprising 77 cases, 18 primary cultures, 4 derived cell lines, 80 patient-derived xenografts and 11 cell-derived xenografts. We comparatively investigated these unique complementary materials using morphofunctional, ultrastructural and flow cytometric assays accompanied by microRNA studies. We found that paragangliomas contain stem-like cells with hybrid mesenchymal/vasculoneural phenotype, stabilized and expanded in the derived cultures. The viability and growth of such cultures depended on the downregulation of the miR-200 and miR-34 families, which allowed high PDGFRA and ZEB1 protein expression levels. Both tumour tissue- and cell culture-derived xenografts recapitulated the vasculoneural paraganglioma structure and arose from mesenchymal-like cells through a fixed developmental sequence. First, vasculoangiogenesis organized the microenvironment, building a perivascular niche which in turn supported neurogenesis. Neuroepithelial differentiation was associated with severe mitochondrial dysfunction, not present in cultured paraganglioma cells, but acquired in vivo during xenograft formation. Vasculogenesis was the Achilles’ heel of xenograft development. In fact, imatinib, that targets endothelial-mural signalling, blocked paraganglioma xenograft formation (11 xenografts from 12 cell transplants in the control group versus 2 out of 10 in the treated group, P = 0.0015). Overall our key results were unaffected by the SDHx gene carrier status of the patient, characterized for 70 out of 77 cases. In conclusion, we explain the biphasic vasculoneural structure of paragangliomas and identify an early and pharmacologically actionable phase of paraganglioma organization. Electronic supplementary material The online version of this article (10.1007/s00401-017-1799-2) contains supplementary material, which is available to authorized users.