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A 19-year-old woman presented to the emergency department with arrhythmia and signs of cardiogenic shock. After a 12-lead electrocardiogram ruled out acute myocardial infarction, and cardiac magnetic resonance showed no sign of cardiomyopathy, cardiac computed tomography angiography (CCTA) was performed, displaying ostial atresia of the right coronary artery. She was thus referred to a specialist centre for congenital cardiovascular disease, where an electrophysiological study observed an arrhythmogenic focus on the posteromedial papillary muscle, which was ablated, and she has been asymptomatic since. When dealing with patients presenting with arrhythmias or cardiogenic shock, and no signs of myocardial infarction or cardiomyopathy, performing CCTA to study the anatomy of the coronary arteries is vital., Competing Interests: The authors have no conflict of interest to disclose with regards to the matters of this article., (© The Author(s) 2025. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Purpose: The aim of the present systematic review was to corroborate existing evidence on how serum25(OH)D levels affect obstructive sleep apnea syndrome (OSAS) severity in the absence of comorbidities., Methods: From inception to May 2024, PubMed, Scopus, and Embase electronic databases were systematically screened to identify randomized controlled trials (RCTs), quasi-RCTs, prospective, and retrospective studies. A strict search protocol was applied following the application of PROSPERO, under the registration number CRD42023468744. The formulated question based on PICO process was: "how do serum25(OH)D levels affect the severity of OSAS or result in enhanced sleep function?". Collected results were finally reviewed for meta-analysis and quality assessment according to the ROBINS-I tool., Results: Data from 24 studies were pooled and divided into 15 case-control studies and 9 cross-sectional studies. All studies involved a total of 2640 OSAS subjects and 933 healthy subjects. All studies underwent qualitative analysis whereas only 20 were collected for meta-analysis. Mild OSAS showed 25(OH)D levels non-statistically significant (P = 0.12) than the healthy patients whereas moderate OSAS (P = 0.004) and severe OSAS (P < 0.001) differed significantly from control groups. Meta-regression suggested that OSAS severity correlated inversely to the deficiency of 25(OH)D serum levels. Qualitative assessment and Egger's test revealed an elevated risk of bias but low presence of publication bias, respectively., Conclusion: Serum levels of 25(OH)D were observed to be inversely proportional to OSAS severity in patients without coexisting morbidities. 25(OH)D levels in mild OSAS patients were not significantly different from non-OSAS patients, suggesting vitamin supplementation to improve potential sleep disorders., Competing Interests: Declarations. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors. Conflict of interest: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript., (© 2024. The Author(s).)

During embryonic and neonatal development, mitochondria have essential effects on metabolic and energetic regulation, shaping cell fate decisions and leading to significant short- and long-term effects on embryonic and offspring health. Therefore, perturbation on mitochondrial function can have a pathological effect on pregnancy. Several shreds of evidence collected in preclinical models revealed that severe mitochondrial dysfunction is incompatible with life or leads to critical developmental defects, highlighting the importance of correct mitochondrial function during embryo-fetal development. The mechanism impairing the correct development is unknown and may include a dysfunctional metabolic switch in differentiating cells due to decreased ATP production or altered apoptotic signalling. Given the central role of mitochondria in embryonic and fetal development, the mitochondrial dysfunction typical of Mitochondrial Diseases (MDs) should, in principle, be detectable during pregnancy. However, little is known about the clinical manifestations of MDs in embryonic and fetal development. In this manuscript, we review preclinical and clinical evidence suggesting that MDs may affect fetal development and highlight the fetal and maternal outcomes that may provide a wake-up call for targeted genetic diagnosis., (© 2024. The Author(s).)

The association between systemic scleroderma and malignancy is well-documented, but there is limited data on the relationship between morphea and malignancy. This study aims to assess the incidence and types of malignancies in morphea patients, comparing demographics, clinical characteristics, treatments, and outcomes between those with and without malignancy. We conducted a retrospective study of 204 morphea patients treated at Rabin Medical Center between 2012 and 2023. Data on demographics, clinical subtypes, comorbidities, treatments, and outcomes were collected. Patients were categorized based on malignancy status and the timing of malignancy relative to their morphea diagnosis. Among the 204 patients (154 women and 50 men, mean age 53.7 ± 20 years), 47 (23%) developed malignancies. In 29 patients (61.7%), malignancy occurred before the onset of morphea; in 23 patients (48.9%), it occurred after morphea. Five patients (10.6%) had malignancies both before and after the diagnosis of morphea. Patients with malignancy were significantly older than those without (64.7 ± 15.1 years vs. 50.3 ± 20 years, p < 0.0001). The all-cause mortality rate was higher in the malignancy group compared to those without malignancy (23.4% vs. 3.8%, p = 0.00002). Moreover, mortality was higher in patients whose malignancy occurred after morphea than in those whose malignancy preceded morphea (26% vs. 17.2%). The most common post-morphea malignancies in our cohort included non-melanoma skin cancer, cervical cancer, breast cancer, stomach cancer, and lung cancer. The most common pre-morphea malignancies included breast cancer, non-melanoma skin cancer, colon cancer, prostate cancer, and testicular cancer. This study suggests potential associations between morphea and malignancies, influenced by patient age, sequence of diagnosis, and treatment regimens. Further control studies are needed to explore these relationships more definitively., (© 2024. The Author(s).)

Background: Dilated cardiomyopathy (DCM) is an etiologically heterogeneous group of diseases of the myocardium. With the rapid evolution in laboratory investigations, genetic background is increasingly determined including many genes with variable penetrance and expressivity. Biallelic NEXN variants are rare in humans and associated with poor prognosis: fetal and perinatal death or severe DCMs in infants., Case Presentation: We describe two male infants with prenatal diagnosis of dilated cardiomyopathy with impaired ventricular contractility. One of the patients showed hydrops and polyhydramnios. Postnatally, a DCM with severely reduced systolic function was confirmed and required medical treatment. In patient 1, Whole Exome Sequencing (WES) revealed a homozygous NEXN variant: c.1156dup (p.Met386fs) while in patient 2 a custom Next Generation Sequencing (NGS) panel revealed the homozygous NEXN variant c.1579&#95;1584delp. (Glu527&#95;Glu528del). These NEXN variants have not been previously described. Unlike the unfavorable prognosis described for biallelic NEXN variants, we observed in both our patients a favorable clinical course over time., Conclusion: This report might help to broaden the present knowledge regarding NEXN biallelic variants and their clinical expression. It might be worthy to consider the inclusion of the NEXN gene sequencing in the investigation of pediatric patients with DCM., (© 2024. The Author(s).)

Personality disorders (PD) are described as enduring patterns of markedly deviant and pervasive inner experiences and behaviors, with onset in adolescence, which lead to severe distress or impairment. Patients suffering from major depressive disorder (MDD) display higher rates of comorbidity with personality disorders, often complicating the treatment, and worsening the outcomes. Borderline personality disorder (BPD) is the most common of PD and is frequently associated with MDD, with which shares several features. The most part of research agrees on the fact that comorbid BPD in MDD patients quite doubles the poor response to treatments. Moreover, no treatment strategy stands out currently to emerge as more effective in these cases, thus urging the call for the need of new approaches. Herein, we revise the current literature on BPD, its neurobiology and comorbidity with MDD, as well as the more recent treatment strategies used. Then, based on its pharmacology, we propose a possible role of trazodone as a valuable tool to approach comorbid BPD-MDD., (© 2024. The Author(s).)

Introduction: Differential diagnosis among subjects with Primary Progressive Aphasia (PPA) can be challenging. Structural MRI can support the clinical profile. Visual rating scales are a simple and reliable tool to assess brain atrophy in the clinical setting. The aims of the study were to establish to what extent the visual rating scales could be useful in the differential diagnosis of PPA, to compare the clinical diagnostic impressions derived from routine MRI interpretations with those obtained using the visual rating scale and to correlate results of the scales in a voxel-based morphometry (VBM) analysis., Method: Patients diagnosed with primary progressive aphasia (PPA) according to current criteria from two centers-Ospedale Maggiore Policlinico of Milan and Hospital Clínic de Barcelona-were included in the study. Two blinded clinicians evaluated the subjects MRIs for cortical atrophy and white matter hyperintensities using two protocols: routine readings and the visual rating scale. The diagnostic accuracy between patients and controls and within PPA subgroups were compared between the two protocols., Results: One hundred fifty Subjects were studied. All the scales showed a good to excellent intra and inter-rater agreement. The left anterior temporal scale could differentiate between semantic PPA and all other variants. The rater impression after the protocol can increase the accuracy just for the logopenic PPA. In the VBM analysis, the scores of visual rating scales correlate with the corresponding area of brain atrophy., Conclusion: The Left anterior temporal rating scale can distinguish semantic PPA from other variants. The rater impression after structured view improved the diagnostic accuracy of logopenic PPA compared to normal readings. The unstructured view of the MRI was reliable for identifying semantic PPA and controls. Neither the structured nor the unstructured view could identify the nonfluent and undetermined variants., (© 2024. The Author(s).)

Objectives: A calcium phosphate extracted from fish bones (CaP-N) was evaluated for enamel remineralization and dentinal tubules occlusion., Methods: CaP-N was characterized by assessing morphology by SEM, crystallinity by PXRD, and composition by ICP-OES. CaP-N morphology, crystallinity, ion release, and pH changes over time in neutral and acidic solutions were studied. CaP-N was then tested to assess remineralization and dentinal tubules occlusion on demineralized human enamel and dentin specimens (n = 6). Synthetic calcium phosphate in form of stoichiometric hydroxyapatite nanoparticles (CaP-S) and tap water were positive and negative controls, respectively. After treatment (brush every 12 h for 5d and storage in Dulbecco's modified PBS), specimens' morphology and surface composition were assessed (by SEM-EDS), while the viscoelastic behavior was evaluated with microindentation and DMA., Results: CaP-N consisted of rounded microparticles (200 nm - 1 µm) composed of 33 wt% hydroxyapatite and 67 wt% β-tricalcium phosphate. In acidic solution, CaP-N released calcium and phosphate ions thanks to the preferential β-tricalcium phosphate phase dissolution. Enamel remineralization was induced by CaP-N comparably to CaP-S, while CaP-N exhibited a superior dentinal tubule occlusion than CaP-S, forming mineral plugs and depositing new nanoparticles onto demineralized collagen. This behavior was attributed to its bigger particle size and increased solubility. DMA depth profiling and SEM showed an excellent interaction between the newly formed mineralized structures and the pristine tissue, particularly at the exposed collagen fibrils., Significance: CaP-N demonstrated very good remineralizing and occlusive activity in vitro, comparable to CaP-S, thus could be a promising circular economy alternative therapeutic agent for dentistry., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: During the last decades, in patients with periodontitis, periodontal treatment has been shown to reduce the potential release of local and systemic biomarkers linked to an early risk of systemic inflammatory disorders. This study evaluated the efficacy of non-surgical-periodontal treatment (NSPT) on growth differentiation factor 15 (GDF-15) and related circulating biomarkers such as glutathione peroxidase 1 (GPx-1), c-reactive protein (hs-CRP), and surfactant protein D (SP-D) in periodontal patients and explored whether subjects who had high GDF-15 levels at baseline showed increased clinical benefits following NSPT at 6-months follow-up., Methods: For this two-arm, parallel randomized clinical trial, patients with periodontitis were randomly allocated to receive quadrant scaling and root-planing (Q-SRP, n = 23, median age 51 years old) or full-mouth disinfection (FMD, n = 23, median age 50 years old) treatment. Clinical and periodontal parameters were recorded in all enrolled patients. The primary outcome was to analyse serum concentrations changes of GDF-15 and of GPx-1, hs-CRP, and SP-D at baseline and at 30, 90, and 180-days follow-up after NSPT through enzyme-linked immunosorbent assay (ELISA) and nephelometric assay techniques., Results: In comparison with FMD, patients of the Q-SRP group showed a significant improvement in clinical periodontal parameters (p < 0.05) and a reduction in the mean levels of GDF-15 (p = 0.005), hs-CRP (p < 0.001), and SP-D (p = 0.042) and an increase of GPx-1 (p = 0.025) concentrations after 6 months of treatment. At 6 months of treatment, there was a significant association between several periodontal parameters and the mean concentrations of GDF-15, GPx-1, hs-CRP, and SP-D (p < 0.05 for all parameters). Finally, the ANOVA analysis revealed that, at 6 months after treatment, the Q-SRP treatment significantly impacted the reduction of GDF-15 (p = 0.015), SP-D (p = 0.026) and the upregulation of GPx-1 (p = 0.045)., Conclusion: The results evidenced that, after 6 months of treatment, both NSPT protocols improved the periodontal parameters and analyzed biomarkers, but Q-SRP was more efficacious than the FMD approach. Moreover, patients who presented high baseline GDF-15 and SP-D levels benefited more from NSPT at 6-month follow-up., Trial Registration: NCT05720481., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Chronic inflammation and cumulative oxidative stress have been theorized as two common pathways of the interconnection between periodontitis and diabetes. Improvement in oxidizing status has been demonstrated in periodontal patients with diabetes treated with proper non-surgical periodontal treatment. In addition to periodontal treatment, Gaseous ozone therapy has been reported to possess anti-inflammatory properties and the ability to stimulate the endogenous antioxidant defence mechanism. To date, the antioxidant effect of gaseous ozone, in addition with periodontal treatment in diabetic patients, has been examined in only one study. The aim of this study was to determine the efficacy of gaseous ozone therapy as an alternative approach to supporting non-surgical periodontal therapy (NSPT), aimed at improving antioxidant machinery and interfering with ROS production on plasma levels in diabetic individuals diagnosed with moderate or severe periodontitis., Methods: One hundred and eighty patients with periodontitis and type 2 diabetes mellitus were randomly assigned to receive non-surgical periodontal treatment (NSPT) plus gaseous ozone therapy (A) NSPT alone (B). Clinical and periodontal parameters -Bleeding on probing (BOP), Periodontal pocket depth (PPD), and Clinical attachment Level (CAL)- and plasma levels of oxidant-antioxidant (TOS- TAOS) levels, glutathione (GSH), and malondialdehyde (MDA) were recorded at baseline and at 3- (T1) and at 6-months (T2) after treatment., Results: Both treatments were efficacious in reducing clinical parameters. However, there were no significant differences regarding oxidative stress parameters in group A compared to group B., Conclusions: In the present study, gaseous ozone therapy did not enhance the effect of periodontal treatment in reducing oxidative stress in plasma levels of periodontitis patients with type II diabetes., Trial Registration: The study was registered with ISRCTN1728169 (23/07/2022)., (© 2023. The Author(s).)

Background: Despite the relevance of telephone-based cognitive screening tests in clinical practice and research, no specific test assessing executive functioning is available. The present study aimed at standardizing and providing evidence of clinical usability for the Italian telephone-based Frontal Assessment Battery (t-FAB)., Methods: The t-FAB (ranging 0-12), comprising two subtests, has two versions: one requiring motor responses (t-FAB-M) and the other verbal responses (t-FAB-V). Three hundred and forty-six Italian healthy adults (HPs; 143 males; age range = 18-96 years; education range = 4-23 years) and 40 participants with neurological diseases were recruited. To HPs, the t-FAB was administered along with a set of telephone-based tests: MMSE, verbal fluency (VF), backward digit span (BDS). The in-person version of the FAB was administered to both HPs and clinical groups. Factorial structure, construct validity, inter-rater and test-retest reliability, t-FAB-M vs. t-FAB-V equivalence and diagnostic accuracy were assessed. Norms were derived via Equivalent Scores., Results: In HPs, t-FAB measures yielded high inter-rater/test-retest reliability (ICC = .78-.94), were internally related (p ≤ .005) and underpinned by a single component, converging with the telephone-based MMSE, VF, BDS (p ≤ .0013). The two t-FAB versions were statistically equivalent in clinical groups (ps of both equivalence bounds < .001). Education predicted all t-FAB scores (p < .001), whereas age only the t-FAB-M score (p ≤ .004). t-FAB scores converge with the in-person FAB in HPs and clinical groups (r s  = .43-.78). Both t-FAB versions were accurate in discriminating HPs from the clinical cohort (AUC = .73-.76)., Discussion: The t-FAB is a normed, valid, reliable and clinically usable telephone-based cognitive screening test to adopt in both clinical and research practice., (© 2022. The Author(s).)

Background: The aim of this study was to evaluate the relationship between frontal sinus shape and facial growth pattern., Methods: The three-dimensional examination was carried out by means of 80 CBCT scans selected from a sample of 1247 records of patients treated, for different reason, at the Department of Biomedical Surgical and Dental Sciences at University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico Milan. The sample (age ranges between 12 and 40 years) was divided according to gender and age in four groups (12-17, 18-20, 21-30, 31-40). Left and right frontal sinus volume (VOL), surface (SUP) and linear maximum width (XMAX), depth (ZMAX) and height (YMAX) were calculated using Mimics Research 17.0 (Materialise N.V., Leuven, Belgium). Cephalometric analysis has been performed for all subjects to categorize the patients depending on their facial growth pattern. Univariate and multivariate regression analysis were performed to investigate any association of frontal sinuses measurements (height, width, depth, volume and surface) and cephalometric variables. P value < 0.05 was considered statistically significant., Results: A total of 160 frontal sinuses were measures in 80 patients: 40 men and 40 women, average age of 23.5 ±14.6. Globally the frontal sinuses had the following average dimensions: volumes of 9055.8 ± 6505 mm 3 and surfaces of 3820.3 ± 2125 mm 2 . The statistical analysis showed that frontal sinus volume was statistically significant (p=0.003) greater for male (11,425 mm 3 ) than female (6597.5 mm 3 ). Similarly, the surface showed to be greater in men than in women (p=0.005). No correlation between age and frontal sinuses characteristics has been found. A statistically significant (p<0.05) increase of frontal sinus depth, surface and volume was correlated with SNB angle. In addition, frontal sinus volume increased in subjects with greater anterior skeletal dimension values and with a superior length of the cranial base. Furthermore, a decrease of ANB has been found related to an increase in frontal sinus volume (p=0.04)., Conclusions: The present study showed a correlation between frontal sinuses dimensions and craniofacial aspects, despite the inter-individual variability of their morphology. The results suggested that young adults in whom the frontal sinuses have reached their maximum size, while vertical growth continues, a larger frontal sinus may be associated with future vertical growth., (© 2022. The Author(s).)

Impaired semantic knowledge is a characteristic feature of some forms of frontotemporal dementia (FTD), particularly the sporadic disorder semantic dementia. Less is known about semantic cognition in the genetic forms of FTD caused by mutations in the genes MAPT , C9orf72 , and GRN . We developed a modified version of the Camel and Cactus Test (mCCT) to investigate the presence of semantic difficulties in a large genetic FTD cohort from the Genetic FTD Initiative (GENFI) study. Six-hundred-forty-four participants were tested with the mCCT including 67 MAPT mutation carriers (15 symptomatic, and 52 in the presymptomatic period), 165 GRN mutation carriers (33 symptomatic, 132 presymptomatic), and 164 C9orf72 mutation carriers (56 symptomatic, 108 presymptomatic) and 248 mutation-negative members of FTD families who acted as a control group. The presymptomatic mutation carriers were further split into those early and late in the presymptomatic period (more than vs. within 10 years of expected symptom onset). Groups were compared using a linear regression model, adjusting for age and education, with bootstrapping. Performance on the mCCT had a weak negative correlation with age (rho = -0.20) and a weak positive correlation with education (rho = 0.13), with an overall abnormal score (below the 5th percentile of the control population) being below 27 out of a total of 32. All three of the symptomatic mutation groups scored significantly lower than controls: MAPT mean 22.3 (standard deviation 8.0), GRN 24.4 (7.2), C9orf72 23.6 (6.5) and controls 30.2 (1.6). However, in the presymptomatic groups, only the late MAPT and late C9orf72 mutation groups scored lower than controls (28.8 (2.2) and 28.9 (2.5) respectively). Performance on the mCCT correlated strongly with temporal lobe volume in the symptomatic MAPT mutation group (rho > 0.80). In the C9orf72 group, mCCT score correlated with both bilateral temporal lobe volume (rho > 0.31) and bilateral frontal lobe volume (rho > 0.29), whilst in the GRN group mCCT score correlated only with left frontal lobe volume (rho = 0.48). This study provides evidence for presymptomatic impaired semantic knowledge in genetic FTD. The different neuroanatomical associations of the mCCT score may represent distinct cognitive processes causing deficits in different groups: loss of core semantic knowledge associated with temporal lobe atrophy (particularly in the MAPT group), and impaired executive control of semantic information associated with frontal lobe atrophy. Further studies will be helpful to address the longitudinal change in mCCT performance and the exact time at which presymptomatic impairment occurs.

Objectives: To report the outcomes of thoracic endovascular aortic repair (TEVAR) for shaggy thoracic aortic aneurysms (STA)., Methods: It is a single center, retrospective, observational, cohort study. Data were collected prospectively between January 2005 and May 2019. STA was defined, based on computed tomography angiography findings, as the presence of an irregular/ulcerated atheroma protruding and/or thrombus thickness ≥ 5 mm protruding into the aortic lumen, and/or occupying more than two thirds of the circumference of the aortic diameter axially. Primary outcomes were early (≤ 30 days) and late survival and freedom from major complication due to end-organ or peripheral ischemic embolization., Results: Nine (2.3%) of 391 patients met the inclusion criteria. Mean age was 71 years ± 10 (range 55-83). Mean aneurysm diameter was 68 mm ± 0.5 (range 60-75). Four patients presented symptomatic: rupture (n = 2), blue toe syndrome (n = 2). TEVAR was performed in 7 of the 9 patients. Operative-related embolization occurred in 1 patient (transient ischemic attack and acute kidney injury). In-hospital mortality was observed in 1 patient following spinal cord ischemia and multiple organ failure development. Median follow-up was 48 months (IQR 5-84). Freedom from major complication due to end-organ or peripheral ischemic embolization was achieved in all patients. No patient developed further localization of STA in the proximal or distal aorta, and did not experience reno-visceral or peripheral atheroembolization episodes., Conclusions: Risk of atheroembolism in STA is still threatening but TEVAR proved to be an effective and durable treatment in this high-risk cohort.

Purpose: To assess a correlation between the shrinkage of the fibroid and the course of the symptoms., Material and Methods: Fourteen patients with symptomatic uterine leiomyomas (mean fibroid volume: 111.45 cm 3 ) underwent percutaneous microwave ablation. Contrast-enhanced MRI follow-up was performed before and after treatment to evaluate the volume shrinkage. Two scores obtained from the Uterine Fibroids Symptom and Quality of Life questionnaire were used to perform a clinical follow-up to evaluate the symptoms and the quality of life at baseline, and at 3, 6 and 12 months after treatment., Results: All patients were treated, no complications occurred. During a mean MR follow-up of 8.1 months we observed shrinkage of the fibroids in all patients (mean 70.3 cm 3 ). During 12 months clinical follow-up, we observed a significant improvement of symptoms and an excellent improvement of quality of life ( p  < .001)., Conclusion: Uterine fibroids percutaneous microwave ablation is a safe tool to obtain a significant improvement in quality of life for all the patients of our cohort.

Objective: The aim of this prospective study was to assess the safety and effectiveness of a new single laparoscopic operation devised to relieve obstructed defecation, gynecologic and urinary symptoms in a large series of female patients with multiorgan pelvic prolapse., Methods: We submitted 384 female patients to laparoscopic pelvic organ prolapse suspension operation, a new technique based on suspension of the middle pelvic compartment, by using a polypropylene mesh and followed up 368 of them, with defecography performed 12 months after surgery and a standardized protocol., Results: The 368 patients were followed-up for 36.3 (±4.4) months, Recurrence rate was 4.9% for obstructed defecation syndrome and 3.3% for stress urinary incontinence. Complication rate was 2.9%. The mean period of daily activity resumption was 16.3 days (±4.8 days). Anorectal and urogynecologic symptoms and scores significantly improved after the operation (P < 0.001), with no worsening of anal continence. Incidence of postoperative fecal urgency was 0%. Postoperative defecography showed a significant (P < 0.001) improvement of all parameters in 315 patients (82%). Short Form 36 Health Survey score significantly improved after the operation (P < 0.01). An excellent/good overall Satisfaction Index was reported by 78.0% of patients., Conclusions: In our experience the Laparoscopic-Pelvic Organ Prolapse Suspension seems to be safe and effective as a 1-stage treatment of associated pelvic floor diseases. Randomized studies with an appropriate control group and longer follow-up are now needed to assess the effectiveness of this promising technique., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2019 American Urogynecologic Society. All rights reserved.)

Outcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. We searched PubMed and EMBASE up to 20 August 2020 to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of intensive care unit admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-four adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14 of 34 adult studies included only hospitalized patients). Risk of death among adult patients was 34% (95% CI, 28-39; N = 3240) in this sample of predominantly hospitalized patients. Patients aged ≥60 years had a significantly higher risk of death than patients <60 years (RR, 1.82; 95% CI, 1.45-2.27; N = 1169). The risk of death in pediatric patients was 4% (95% CI, 1-9; N = 102). RR of death comparing patients with recent systemic anticancer therapy to no treatment was 1.17 (95% CI, 0.83-1.64; N = 736). Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, have a high risk of dying. Patients ≥60 years have significantly higher mortality; pediatric patients appear to be relatively spared. Recent cancer treatment does not appear to significantly increase the risk of death., (© 2020 by The American Society of Hematology.)

Background: Miescher's cheilitis granulomatosa (MCG) is a rare chronic inflammatory disease and is known as the monosymptomatic clinical form of Melkersson-Rosenthal syndrome (MRS). It is characterised by swelling of one or both lips and more frequently affects the upper lip. Histopathological findings show the presence of numerous inflammatory infiltrates and granuloma formations. Pharmacological treatments and surgery have provided results that are positive yet insufficiently stable in the long term. The clinical case described is of a 68-year-old female patient with a diagnosis of MCG of the upper lip., Case Presentation: The patient was diagnosed and treated at the Oral Medicine and Oral Pathology outpatient clinic of Maxillofacial and Odontostomatology Unit, Fondazione Cà Granda IRCCS Ospedale Maggiore Policlinico. The patient was recommended localised treatments of photobiomodulation (PBM) using a diode laser with a 635 nm and 980 nm dual-wavelength ( λ ) approach, a 600-micron fibre, and a handpiece with a 1-cm-diameter lens at 300 mW. Three treatments a week were administered for four weeks for a total of 12 treatment sessions ( T 1 - T 12 ). After that, the patient had a long follow-up period of about 2 years. The therapeutic results were clear from the initial stages of treatment. There was an immediate, gradual, and consistent reduction in labial swelling. A reduction in the size of the lip by about 35% at T 10 - T 12 was observed, returning the size and volume of the upper lip within the normal clinical range. The painful symptoms subsided after the seventh treatment ( T 7 ). The histopathological check at 3 months and the follow-up in particular confirmed the disease was in remission with satisfactorily stable treatment results. Moreover, the patient did not use any other treatments on the area from the early laser treatments through to the end of the follow-up period., Conclusions: Our experience describes a clinical case of MCG treated with PBM and effectively resolved with a reduction of the lip swelling. The real success of the treatment emerged over time, showing that the tissue healing was stable. In absence of any collateral phenomena, this confirms the effective and documented therapeutic potential of PBM for chronic inflammatory infiltrates., Competing Interests: Competing interestsWe have no conflicts of interest or connected interests with this work. We declare that we have no competing financial interest., (© The Author(s) 2020.)

Background:  Limited data exist on the clinical impact of low-responding inhibitors and the requirement for immune tolerance induction (ITI) treatment to establish tolerance, reduce bleeding, and improve outcome. The aim of this article is to describe the therapeutic management of children with severe hemophilia A and low-responding inhibitors and its effect on bleeding phenotype., Methods:  The REMAIN (Real-life Management of Inhibitors) study is a satellite study of the PedNet registry. It included unselected children with severe hemophilia A (factor VIII [FVIII] < 0.01 IU/mL) born between January 1, 1990 and December 31, 2009 who developed clinically relevant inhibitors and were followed-up for at least 3 years after the first positive inhibitor test., Results:  A total of 260 patients with inhibitors were identified and 68 of them (26%) had low-responding inhibitors (peak < 5 BU/mL). Five patients were lost to follow-up and 63 were included in this study. The median follow-up was 3.7 years (interquartile range: 3.0-7.5). ITI was started in 51/63 (81%) patients. The median time from ITI start to first negative inhibitor titer was similar with low-dose and high-dose ITI regimens (2.5 and 3.1 months, respectively). Ten of the 12 patients who did not receive ITI were treated with regular prophylaxis and reached a negative titer after a median of 6.5 months. Bleeding rate was low in all patients with no difference between treatment regimens., Conclusion:  In children with low-responding inhibitors negative titers were reached with regular FVIII treatment irrespective of the regimen (i.e., prophylaxis or ITI)., Competing Interests: H.M.v.d.B. has received research grants from Bayer, Shire/Takeda, Novo Nordisk, CSL Behring, Pfizer, and Sobi; M.E.M. has acted as paid speaker/consultant for Bayer Healthcare, CSL Behring, Grifols, Roche, Kedrion, Pfizer, Novo Nordisk, Octapharma, Sobi, and Shire/Takeda; C.K. reports grants and personal fees from Bayer Vital GmbH, Biotest AG, CSL Behring, Grifols, Intersero, Pfizer, Sanofi, Sobi, Takeda, Jansen, Roche/Chugai, MSD, and Novo Nordisk; R.D.O. has received personal fees and nonfinancial support from Shire/Takeda, CSL Behring, LFB, Novo Nordisk, Octapharma, Roche, and Spark; H.P. has received honoraria from Bayer, Baxalta, CSL Behring, Novo Nordisk, Roche, Sobi, and Pfizer; T.S.M. has no conflicts to disclose; B.N. has received fees and research grants from Sanofi, Sobi, CSL Behring, and Bayer; E.S. has acted as paid speaker/consultant for Bayer Healthcare, CSL Behring, Grifols, Roche, Kedrion, Pfizer, Novo Nordisk, Octapharma, Sobi, Spark, Uniqure, and Shire/Takeda., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Half of the deaths recorded in non-surgical patients attributable to venous thromboembolism (VTE) affect those with stroke. The uncertain benefit of anticoagulant therapy has increased interest in non-pharmacological intervention to prevent VTE., Aim: To evaluate the efficacy and safety of non-pharmacological interventions to prevent VTE in stroke patients., Methods: Overview of systematic reviews with retrieval of documents in compliance with the PICOS Framework and through a research strategy implemented on 4 April 2019 in six biomedical databases and in the PROSPERO registry. The tools used to assess the methodological quality and the risk of bias were the AMSTAR checklist and the ROBIS tool, respectively. The results have been synthesized with narrative modality., Results: Seven systematic reviews of different methodological quality and risk of bias met the inclusion criteria. The non-pharmacological interventions of prophylaxis used are graduated compression stockings (GCS) and intermittent pneumatic compression devices (IPCD). The first has no effect on VTE and has important side effects, the second is promising in reducing mortality from all causes and decreases the incidence of deep vein thrombosis., Discussion: The use of IPCD, despite the efficacy observed, should be reserved, after a risk assessment of VTE and a subgroup analysis, for patients who can derive the maximum benefit from the intervention., Conclusions: In stroke patients the use of GCS to prevent VTE is not recommended because it is not superior to standard care and can cause damage. IPCD as a intervention of prophylaxis appears to be effective but further confirmation is needed from future studies.

Resistance can be the result of secondary tissue variants (STVs), which restore the open reading frame of the germline BRCA allele, producing functional BRCA protein in germline BRCA1/2 (BRCA) pathogenic variant (PV) carriers, treated with platinum-based chemotherapy or poly-(ADP-ribose) polymerase inhibitors (PARP-1). We reported recently a BRCA2 mutant high grade serous ovarian cancer (HGSOC) patient with acquired resistance to the PARP-1 olaparib due to a STV detected by next generation tumor sequencing (NGTS). The aim of this study was to evaluate the versatility of the high-resolution melting analysis (HRMA) obtained by magnetic induction cycler (MIC) to monitor the BRCA2 status in formalin-fixed paraffin-embedded (FFPE) tissue samples of this patient and to compare the results obtained by NGTS. HRMA highlighted the BRCA2 STV previously detected in the IIIrd HGSOC recurrence following the tissue BRCA2 tissue status comparing the high resolution melting profiles (HRMPs). HRMPs differentiate not only BRCA2 alleles, but also their different allele abundance. We underline that (1) the MIC uses a latest generation technology guaranteeing temperature uniformity and maintenance in each well allowing high and accurate performance to obtain reported results and (2) the HRMA maintains a high sensitivity and specificity when it is performed on FFPE samples. Finally, this study represents an additional use of the HRMA, confirming its extreme versatility in the diagnostic environment.

Background: High serum phosphate (Pi) levels strongly associate with cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients with vascular calcification playing a major role in the pathogenesis of related cardiovascular disease. High-Pi challenged vascular smooth muscle cells (VSMCs) undergo simil-osteoblastic transformation and actively deposit calcium-phosphate crystals. Iron-based Pi-binders are used to treat hyperphosphatemia in CKD patients., Methods: In this study, we investigated the direct effect of iron citrate on extracellular matrix (ECM) modification induced by high-Pi, following either prophylactic or therapeutic approach., Results: Iron prophylactically prevents and therapeutically blocks high-Pi induced calcification. Masson's staining highlights the changes of muscular ECM that after high-Pi stimulation becomes fibrotic and which modifications are prevented or partially reverted by iron. Interestingly, iron preserves glycogen granules and either prevents or partially reverts the formation of non-glycogen granules induced by high-Pi. In parallel, iron addition is able to either prevent or block the high-Pi induced acid mucin deposition. Iron inhibited calcification also by preventing exosome osteo-chondrogenic shift by reducing phosphate load (0,61 ± 0.04vs0,45 ± 0.05, PivsPi + Fe, p < 0,05, nmol Pi/mg protein) and inducing miRNA 30c (0.62 ± 0.05vs3.07 ± 0.62; PivsPi + Fe, p < 0.01, relative expression). Studying aortic rings, we found that iron significantly either prevents or reverts the high-Pi induced collagen deposition and the elastin decrease, preserving elastin structure (0.7 ± 0.1 vs 1.2 ± 0.1; Pi vs Pi + Fe, p < 0.05, elastin mRNA relative expression)., Conclusions: Iron directly either prevents or partially reverts the high-Pi induced osteo-chondrocytic shift of ECM. The protection of muscular nature of VSMC ECM may be one of the mechanisms elucidating the anti-calcific effect of iron., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Emicizumab, a bispecific humanized monoclonal antibody, bridges activated factor IX (FIX) and FX to restore the function of missing activated FVIII in hemophilia A. Emicizumab prophylaxis in children with hemophilia A and FVIII inhibitors was investigated in a phase 3 trial (HAVEN 2). Participants, previously receiving episodic/prophylactic bypassing agents (BPAs), were treated with subcutaneous emicizumab: 1.5 mg/kg weekly (group A), 3 mg/kg every 2 weeks (group B), or 6 mg/kg every 4 weeks (group C). Pharmacokinetics, safety, and efficacy (including an intraindividual comparison of participants from a noninterventional study) were evaluated. Eighty-five participants aged <12 years were enrolled. In group A (n = 65), the annualized rate of treated bleeding events (ABRs) was 0.3 (95% confidence interval [CI], 0.17-0.50), and 77% had no treated bleeding events. Intraindividual comparison of 15 participants who previously took BPA prophylaxis showed that emicizumab prophylaxis reduced the ABR by 99% (95% CI, 97.4-99.4). In groups B (n = 10) and C (n = 10), ABRs were 0.2 (95% CI, 0.03-1.72) and 2.2 (95% CI, 0.69-6.81), respectively. The most frequent adverse events were nasopharyngitis and injection-site reactions; no thrombotic events occurred. Two of 88 participants developed antidrug antibodies (ADAs) with neutralizing potential, that is, associated with decreased emicizumab plasma concentrations: 1 experienced loss of efficacy, and, in the other, ADAs disappeared over time without intervention or breakthrough bleeding. All other participants achieved effective emicizumab plasma concentrations, regardless of the treatment regimen. Emicizumab prophylaxis has been shown to be a highly effective novel medication for children with hemophilia A and inhibitors. This trial was registered at www.clinicaltrials.gov as #NCT02795767., (© 2019 by The American Society of Hematology.)

Introduction: The habit of teenagers and young adults to take alcoholic beverages mixed with Energy Drinks (AmED) is increasing. Epidemiological data are of concern but awareness of the problem between consumers and health workers is scarce., Objective: To compare the effects and damages from consumption of AmED compared to alcohol., Metodi: Finding documents through the interrogation of seven biomedical databases. Overview of systematic reviews assessed for methodological quality and risk of bias respectively with the AMSTAR checklist and ROBIS tool with narrative synthesis of results., Results: Six systematic reviews of low quality and high risk of bias met the inclusion criteria. The intake of AmED seems to determine the increase in state of vigilance, reduction of sedation and possible effects at physiological level; there are no significantly different cognitive or psychomotor effects. The evidence to support a lower perception of alcohol intoxication is insufficient; controversial are those in favour of an increase in alcohol intake or risky behavior., Discussion and Conclusions: The results of experimental studies, which unlike nonexperimental could identify a cause-effect relationship, are often statistically insignificant and do not lead to a unanimous consensus on the different effects/damages of two consumption patterns. The authors of three reviews declare conflicts of interest with an ED producer, raising the problem of industry's influence on research. The current evidence is insufficient to confirm or refute the hypothesis that intake of AmED results in significantly different effects/damage compared to alcohol. However, the magnitude of phenomenon must act as a push for further studies promoted by independent researchers.

The present multicentric (n = 11 laboratories) study aimed to identify conversion factors from copies/mL to international units (IU)/mL for the normalization of HCMV DNA load using the first WHO International Standard for HCMV nucleic acid amplification techniques and to enhance interlaboratory agreement of HCMV DNA quantification methods. Study protocols for whole blood and plasma (extraction and amplification) were performed to calculate conversion factors from HCMV DNA copy number to IU. The greatest variability was observed in samples with lower HCMV concentrations (3.0 Log 10 ) in both biological matrices. Overall, 73.1% (206/282) of whole blood and 82.2% (324/394) of plasma samples analyzed fell within an acceptable variation range (±0.5 Log 10 difference). An average of 0.64 (range 0.21-1.17) was the conversion factor calculated for the HCMV whole blood panel and 0.82 (range 0.39-2.2) for the HCMV plasma panel., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Vascular calcification (VC) is common in dialysis and non-dialysis chronic kidney disease (CKD) patients, even in the early stage of the disease. For this reason, it can be considered a CKD hallmark. VC contributes to cardiovascular disease (CVD) and increased mortality among CKD patients, although it has not been proven. There are more than one type of VC and every form represents a marker of systemic vascular disease and is associated with a higher prevalence of CVD in CKD patients, as shown by several clinical studies. Major risk factors for VC in CKD include: Increasing age, dialysis vintage, hyperphosphatemia (particularly in the setting of intermittent or persistent hypercalcemia), and a positive net calcium and phosphate balance. Excessive oral calcium intake, including calcium-containing phosphate binders, increases the risk for VC. Moreover, it has been demonstrated that there is less VC progression with non-calcium-containing phosphate binders. Unfortunately, until now, a specific therapy to prevent progression or to facilitate regression of VC has been found, beyond careful attention to calcium and phosphate balance.

Reduction of the inappropriate use of antibiotics in clinical practice is one of the main goals of the Società Italiana di Medicina Interna (SIMI) choosing wisely campaign. We conducted a systematic review of secondary studies (systematic reviews and guidelines) to verify what evidence is available on the duration of antibiotic treatment in Pneumonia. A literature systematic search was performed to identify all systematic reviews and the three most cited and recent guidelines that address the duration of antibiotic therapy in pneumonia. Moreover, a meta-analysis of non-duplicate data from randomized controlled trials (RCTs) considered in the enrolled systematic reviews was performed together with a trial sequential analysis to identify the need for further studies. Two systematic reviews on antibiotic duration in community-acquired pneumonia (CAP) for a total of 17 RCTs (2764 patients) were enrolled in our study. Meta-analysis of non-duplicate RCTs show a non-significant difference in rate of treatment failure between short (≤ 7 days) and long (> 7 days) antibiotic treatment course: RR 1.05 (95% CI, 0.82-1.36). The trial sequential analysis suggests that further data would not affect current evidence or become clinically relevant. Selected guidelines suggest consideration of a short course, with a low grade of evidence and without citing the already published systematic reviews. Antibiotic treatment of CAP for ≤ 7 days is not associated with a higher rate of treatment failure than longer courses and should thus be taken in consideration. Guidelines should upgrade the evidence on this topic.

Vitamin K is a composite term referring to a group of fat-soluble vitamins that function as a cofactor for the enzyme γ-glutamyl carboxylase (GGCX), which activates a number of vitamin K-dependent proteins (VKDPs) involved in haemostasis and vascular and bone health. Accumulating evidence demonstrates that chronic kidney disease (CKD) patients suffer from subclinical vitamin K deficiency, suggesting that this represents a population at risk for the biological consequences of poor vitamin K status. This deficiency might be caused by exhaustion of vitamin K due to its high requirements by vitamin K-dependent proteins to inhibit calcification., Competing Interests: The authors declare no conflict of interest.

Angioedema is a self-limiting edema of the subcutaneous or submucosal tissues due to localised increase of microvascular permeability whose mediator may be histamine or bradykinin. Patients present to emergency department when angioedema involves oral cavity and larynx (life-threatening conditions) or gut (mimicking an acute abdomen). After initial evaluation of consciousness and vital signs to manage breathing and to support circulation if necessary, a simple approach can be applied for a correct diagnosis and treatment. Forms of edema such as anasarca, myxedema, superior vena cava syndrome and acute dermatitis should be ruled out. Then, effort should be done to differentiate histaminergic from non-histaminergic angioedema. Concomitant urticaria and pruritus suggest a histaminergic origin. Exposure to allergens and drugs (mainly ACE inhibitors and non steroidal anti-inflammatory drugs) should be investigated as well as a family history of similar symptoms. Allergic histaminergic angioedema has a rapid course (minutes) whereas non histaminergic angioedema is slower (hours). Since frequently the intervention needs to be immediate, the initial diagnosis is only clinical. However, laboratory tests can be subsequently confirmatory. Allergic angioedema is sensitive to standard therapies such as epinephrine, glucocorticoids and antihistamines whereas non histaminergic angioedema is often resistant to these drugs. Therapeutic options for angioedema due C1-inhibitor deficiencies are C1-inhibitor concentrates, icatibant and ecallantide. If these drugs are not available, fresh frozen plasma can be considered. All these medications have been used also in ACE inhibitor-induced angioedema with variable results thus they are not currently recommended whereas experts agree on the discontinuation of the causative drug., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Cushing disease (CD) represents the principal cause of endogenous hypercortisolism. The first-line therapy of CD is surgical removal of the ACTH-secreting pituitary adenoma, which is generally followed by adrenal insufficiency (AI)., Objective: To analyze the recovery of AI in patients with CD after pituitary surgery in relation with recurrence and persistent remission of CD., Patients and Methods: We performed a retrospective analysis of patients with CD who met the following inclusion criteria: adult age, presence of AI 2 months after the surgical intervention, and a minimum follow-up of 3 years after the surgical intervention., Results: Sixty-one patients were followed for a median of 6 years. Ten (16.4%) patients recurred during follow-up. The patients who restored adrenal function did so after a median time of 19 months, with a significantly shorter time in the recurrence group (12.5 vs. 25 months, p = 0.008). All 10 patients who recurred recovered their adrenal function within 22 months. The recovery rate of AI in the persistent remission group was 37.3% (19/51) at 3 years and 55.8% (24/43) at 5 years. In all patients the duration of AI was negatively associated with disease recurrence., Conclusion: The duration of postsurgical AI in patients with recurrent CD is significantly shorter than that in patients with persistently remitted CD, and this parameter may be a useful predictor of recurrence. Patients showing a normal pituitary-adrenal axis within 2 years after surgery should be strictly monitored as they are at higher risk of disease relapse., (© 2019 S. Karger AG, Basel.)

The development of FVIII inhibitory antibodies is currently the most challenging complication of treatment, affecting ~30% of severe hemophilia A patients. These inhibitors inactivate FVIII, rendering the treatment ineffective, causing disability and increasing morbidity and mortality. Inhibitor development results from a complex multicausal immune response involving both genetic and environmental risk factors. One of the most important modifiable risk factors is the source of FVIII products, eg, plasma-derived or recombinant FVIII. Other environmental risk factors, such as age at first treatment, regimen, and intensity of treatment, could contribute to inhibitor development. Severe bleeds, surgery, concomitant infections, or vaccinations may all be events initiating danger signaling resulting in an immune reaction towards administered FVIII. All in all, the etiology of inhibitor development still remains unclear. The risk factors have been stratified into genetic and environmental, but there are no definitive data to determine the impact of each of them.

Rheumatoid arthritis and spondyloarthritis are inflammatory joint disorders with an autoimmune pathogenesis and systemic involvement. The skin is one of the most frequently affected extraarticular sites with a number of manifestations or distinct diseases, including common conditions, such as rheumatoid nodules and psoriasis, and rare diseases like neutrophilic dermatoses. The latter are clinically characterised by polymorphic lesions, including pustules, bullae, abscesses, papules, nodules, plaques and ulcers, and histologically by neutrophil-rich inflammatory infiltrates. Inflammatory joint disorders and neutrophilic dermatoses share a number of pathophysiological features related to their cytokine overexpression profile. Moreover, any organ system can be potentially involved in neutrophilic dermatoses, giving rise to the concept of neutrophilic disease. Among the extracutaneous manifestations of neutrophilic disease, joint involvement is regarded as the most common. It is not associated with erosions and disability and usually responds to treatment for skin involvement, consisting of systemic corticosteroids and, in refractory cases, immunosuppressants or biologics. Arthritis may also be the initial manifestation of rheumatoid arthritis or spondyloarthritis, which has a chronic or recurrent course and requires a continuous treatment with synthetic or biologic disease-modifying anti-rheumatic drugs. If not properly treated, they may be associated with disability and reduced quality of life. Skin lesions occurring during the course of rheumatoid arthritis and spondyloarthritis require a multidisciplinary approach envisaging the collaboration of dermatologists and rheumatologists in order to achieve early diagnosis and treatment. Several biomarkers may help the clinician in the differential diagnosis of arthritis while histology is pivotal for the correct classification of the skin disease. However, in some cases, only regular follow-up allows a definite diagnosis. In this review article, we focus on the prototypic neutrophilic dermatoses like pyoderma gangrenosum, Sweet's syndrome, hidradenitis suppurativa and their syndromic forms as well as on their articular involvement, providing a simple approach for their diagnosis and therapy.

Introduction: Prevention of central venous access devices (CVAD) occlusion is crucial to the continuity and quality of care. There is wide consensus on the need to carry out a periodic flushing of the lumen of device in order to ensure its patency. The most commonly used solutions are the heparin solution (HS) and the physiological solution (NaCl 0.9% - PS). There are still controversial opinions on HS's effectiveness over PS., Objective: To evaluate the effectiveness of HS compared to PS to prevent occlusion in CVAD., Methods: A search strategy on four electronic databases (The Cochrane Library, Medline, Embase, CINAHL) was implemented on April 4, 2017. Records returned were independently analyzed; those complying with inclusion criteria were found in full text. They've been included systematic reviews of RCT or quasi-experimental studies that have compared the use of HS with PS. The quality assessment of reviews was done with AMSTAR checklist., Results: Seven moderate-high quality systematic reviews met inclusion criteria. HS is was not superior to PS in preventing CVAD occlusions., Discussion: Reviews included were of high quality methodological. The statistical heterogeneity between RCT was low while the clinical and methodological heterogeneity was high., Conclusions: HS was no longer effective than PS to prevent CVAD occlusions. Waiting for better quality studies to evaluate the overall DAVC management process, it seems reasonable to recommend using PS.

Neutrophilic dermatoses are a group of conditions characterized by the accumulation of neutrophils in the skin and clinically presenting with polymorphic cutaneous lesions, including pustules, bullae, abscesses, papules, nodules, plaques and ulcers. In these disorders, the possible involvement of almost any organ system has lead to coin the term 'neutrophilic diseases'. Neutrophilic diseases have close clinicopathological similarities with the autoinflammatory diseases, which present with recurrent episodes of inflammation in the affected organs in the absence of infection, allergy and frank autoimmunity. Neutrophilic diseases may be subdivided into three main groups: (1) deep or hypodermal forms whose paradigm is pyoderma gangrenosum, (2) plaque-type or dermal forms whose prototype is Sweet's syndrome and (3) superficial or epidermal forms among which amicrobial pustulosis of the folds may be considered the model. A forth subset of epidermal/dermal/hypodermal forms has been recently added to the classification of neutrophilic diseases due to the emerging role of the syndromic pyoderma gangrenosum variants, whose pathogenesis has shown a relevant autoinflammatory component. An increasing body of evidence supports the role of pro-inflammatory cytokines like interleukin (IL)-1-beta, IL-17 and tumour necrosis factor (TNF)-alpha in the pathophysiology of neutrophilic diseases similarly to classic monogenic autoinflammatory diseases, suggesting common physiopathological mechanisms. Moreover, mutations of several genes involved in autoinflammatory diseases are likely to play a role in the pathogenesis of neutrophilic diseases, giving rise to regarding them as a spectrum of polygenic autoinflammatory conditions. In this review, we focus on clinical aspects, histopathological features and pathophysiological mechanisms of the paradigmatic forms of neutrophilic diseases, including pyoderma gangrenosum, Sweet's syndrome, amicrobial pustulosis of the folds and the main syndromic presentations of pyoderma gangrenosum. A simple approach for diagnosis and management of these disorders has also been provided.

Spinal ependymomas are predominantly slow-growing lesions constituting approximately 30-88% of primary spinal intramedullary tumors. They usually present as circumscribed lesions, with regular margins and a clear surgical plane. Gross-total resection is often feasible and potentially curative but neurosurgeons should keep in mind that the ultimate goal of surgery is the preservation of spinal cord function. We present the surgical technique to safely resect an intramedullary ependymoma using a posterior median sulcus approach. A brief description of current management of this pathology is also presented., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objectives: Raynaud's phenomenon (RP) can be the first manifestation of systemic sclerosis (SSc) or other connective tissue diseases (CTDs), often preceding an overt disease by years. It is not known if markers of endothelial damage are detectable in those RP patients who subsequently develop a CTD., Methods: We studied 82 RP patients at their first evaluation to correlate the levels of endothelial markers with the subsequent development of an overt disease 36months later. We measured plasma levels of tissue-type plasminogen activator (t-PA) and von Willebrand factor (vWF), two markers of endothelial damage, and interleukin-6 (IL-6), a pro-inflammatory cytokine. Thirty sex- and age-matched healthy subjects (HS) served as controls., Results: At baseline, 67 patients showed capillaroscopic normal pattern (CNP) and 15 patients, of which 11 were very early SSc, had capillaroscopic scleroderma pattern (CSP). Plasma levels of t-PA, vWF and IL-6 were higher in patients with CNP (p=0.0001) than in HS and even much higher in patients with CSP (p=0.0001). In patients with CNP and RP of recent onset (<18months), vWF plasma levels were higher when autoantibodies were present (p=0.020). After 36months, among 48 RP patients with CNP who remained in follow-up, 24 were diagnosed as primary and 24 as secondary RP. In secondary RP, basal levels of t-PA, IL-6 and particularly vWF were higher than in primary RP (p=0.005, p=0.004, p=0.0001 respectively) and HS (p=0.0001 for all)., Conclusions: Our findings indicate that markers of endothelial damage are elevated in RP patients who subsequently develop SSc or other CTDs, even in the absence of capillaroscopic abnormalities., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Liver enzymes appear to be involved in oral lichen planus (OLP), but it is not known whether the elevation develops concomitantly with exacerbations of disease. We compared the levels of serum hepatic aspartate (AST) and alanine (ALT) aminotransferases as markers of OLP exacerbation in patients with chronic hepatitis C from those with chronic liver disorders, seronegative for hepatitis C virus (HCV)., Methods: We studied 71 patients with OLP, (48 HCV seropositive and 23 HCV seronegative with chronic liver diseases) measuring AST and ALT. Association of HCV infection status with serum aminotransferase levels in relation to several types of OLP, exacerbations, and clinical score was studied by means of logistic and linear regression (correcting for age and sex)., Results: Of 476 patients screened, 71 were eligible for the study. Patients in the HCV seropositive group had more elevation of AST and ALT levels (mean level, 51.0 U/l; normal level, <45) than patients in the HCV seronegative group (mean level, 47.5 U/l). Mean serum AST and ALT exceeded the upper limit of the normal range in 33 of 48 (68.8%) in the HCV antibody-positive group and in 9 of 23 (39.5%) in the HCV antibody-negative group. Exacerbations of OLP were more frequent in the high-level AST and ALT group, while HCV status group played a minor role., Conclusions: Among patients with OLP, mild elevation in aminotransferase levels was more common in patients infected with HCV. AST and ALT concentrations were elevated in association with exacerbation of OLP., (© 2017 The International Society of Dermatology.)

Background: Patients with acute heart failure (AHF) have high rates of attendance to emergency departments (EDs), with significant health care costs., Objectives: We aimed to describe the clinical characteristics of patients attending Italian EDs for AHF and their diagnostic and therapeutic work-up., Methods: We carried out a retrospective analysis on 2683 cases observed in six Italian EDs for AHF (January 2011 to June 2012)., Results: The median age of patients was 84 years (interquartile range 12), with females accounting for 55.8% of cases (95% confidence interval [CI] 53.5-57.6%). A first episode of AHF was recorded in 55.3% (95% CI 55.4-57.2%). Respiratory disease was the main precipitating factor (approximately 30% of cases), and multiple comorbidities were recorded in > 50% of cases (history of acute coronary syndrome, chronic obstructive pulmonary disease, diabetes, chronic kidney disease, valvular heart disease). The treatment was based on oxygen (69.7%; 67.9-71.5%), diuretics (69.2%; 67.9-71.5%), nitroglycerin (19.7%; 18.3-21.4%), and noninvasive ventilation (15.2%; 13.8-16.6%). Death occurred within 6 h in 2.5% of cases (2.0-3.1%), 6.4% (5.5-7.3%) were referred to the care of their general practitioners within a few hours from ED attendance or after short-term (< 24 h) observation 13.9% (12.6-15.2%); 60.4% (58.5-62.2%) were admitted to the hospital, and 16.8% (15.4-18.3%) were cared for in intensive care units according to disease severity., Conclusions: Our study reporting the "real-world" clinical activity indicates that subjects attending the Italian EDs for AHF are rather different from those reported in international registries. Subjects are older, with a higher proportion of females, and high prevalence of cardiac and noncardiac comorbidities., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis usually manifesting as skin ulcers with undermined erythematous-violaceous borders. It may be isolated, associated with systemic conditions or occurring in the context of autoinflammatory syndromes such as PAPA (pyogenic arthritis, PG and acne), PASH (PG, acne and suppurative hidradenitis) or PAPASH (pyogenic arthritis, acne, PG and suppurative hidradenitis). From a physiopathological point of view, all these conditions share common mechanisms consisting of over-activation of the innate immune system leading to increased production of the interleukin (IL)-1 family and 'sterile' neutrophil-rich cutaneous inflammation. From a genetic point of view, a number of mutations affecting the proteins of the inflammasome complex (the molecular platform responsible for triggering autoinflammation) or the proteins that regulate inflammasome function have been described in these disorders. As these debilitating entities are all associated with the over-expression of IL-1 and tumour necrosis factor (TNF)-α, biological drugs specifically targeting these cytokines are currently the most effective treatments but, given the emerging role of IL-17 in the pathogenesis of these syndromes, IL-17 antagonists may represent the future management of these conditions.

Introduction: Repositioning regimen is an intervention recommended by guidelines and traditionally used in daily care practice but its benefit for preventing pressure injuries (PI) is not clinically proved., Objective: To determine the effect of repositioning regimen to prevent PI., Methods: A research on five electronic databases (The Cochrane Library, Medline, Embase, CINAHL, Web of Science) was conducted on March 23, 2017. Records returned by the search strategy were independently analyzed and those that respected inclusion criteria have been found in full text. In synopsis have been included systematic reviews of controlled clinical trials or quasi-experimental studies that compare repositioning regimen with usual care. The AMSTAR checklist has been used for quality evaluation., Results: Five systematic reviews met inclusion criteria. The methodological quality of included studies have been very heterogeneous. Compared to usual cares, intervention is not associated with a statistically significant reduction of PI., Discussion: A few and small available studies do not allow to ascertain a benefit from the intervention, if any. At the moment, the application of an individualized repositioning regimen seems a reasonable solution. Further researches are needed to confirm that a more frequent repositioning and a 30° lateral decubitus intake help to prevent PI. It is also necessary to evaluate the economic impact, the acceptability and risks associated with the intervention., Conclusion: It is still unclear the role of repositioning regimen to prevent PI.