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Patients with indolent non-Hodgkin lymphomas (NHL) may often be followed up only with observation, reserving chemotherapy in case of spread. Patients with chronic HCV infection and B cell NHL frequently undergo regression of lymphoproliferative disease once HCV infection is eradicated by treatment. Interferon (IFN)-based therapy has been the treatment of choice for years, remaining unclear whether it is effective in B cell NHL directly or through HCV eradication, since IFN is effective in both HCV infection and B cell NHL. IFN therapy for HCV infection became obsolete with the advent of the well tolerated direct-acting antiviral agents (DAAs), whose excellent efficacy in treating patients with chronic HCV infection and B cell NHL has been recently highlighted. We treated a 53-year-old woman with chronic HCV infection and marginal zone lymphoma (MZL) with elbasvir plus grazoprevir in 2018, with complete remission and persisting excellent results: sustained virological response 24 weeks after treatment (SVR24). The exclusive role of HCV eradication in B cell NHL regression is also underlined.

Introduction Skin tags are benign lesions, that often represent only an aesthetic problem; if subjected to trauma, they can occasionally bleed with possible infection and pain. When they occur in the preauricular region, attention should be paid to the diagnosis and approach; in fact, controversy exists in the differential diagnosis between hair follicle nevi, accessory tragus, and skin tag. Misdiagnosis and failure of treatment can lead to serious consequences, such as chondritis. Materials and Methods In our retrospective study, we evaluated 19 newborns affected by single, unilateral skin tag in the preauricular region. Each patient underwent a careful clinical examination; lesions without a pilosebaceous unit and with a thin, soft pedicle were treated in the nursery with Ligaclip (Johnson & Johnson). Results Skin tag falls between day 7 and 10. We had no cases of edema, cellulitis, clip loss, or bleeding. Scarring results were extremely satisfactory at 3-month follow-up. Conclusion We believe that after a careful clinical examination, cases of skin tags in the preauricular area can be selected and treated with Ligaclip. This procedure can be considered rapid, safe, economical, and simple in the newborn patients.

Background This study aimed to classify the pathomorphology of impacted proximal humeral fractures according to the control volume theory, with the intention to introduce a severity index to support surgeons in decision making. Methods In total, 50 proximal humeral fractures were randomly selected from 200 medical records of adult patients treated from 2009 to 2016. Four nonindependent observers used 2 different imaging modalities (computed tomography scans plus volume rendering; 3D model) to test the classification reliability. A fracture classification system was created according to the control volume theory to provide simple and understandable patterns that would help surgeons make quick assessments. The impacted fractures table was generated based on an evaluation of the calcar condition, determined by the impairment of a defined volumetric area under the cephalic cup and the humeral head malposition. In addition to the main fracture pattern, the comminution degree (low, medium, high), providing important information on fracture severity, could also be evaluated. Results From 3D imaging, the inter- and intraobserver reliability revealed a k value (95% confidence interval) of 0.55 (0.50-0.60) and 0.91 (0.79-1.00), respectively, for the pattern code, and 0.52 (0.43-0.76) and 0.91 (0.56-0.96), respectively, for the comminution degree. Conclusions The new classification provides a useful synoptic framework for identifying complex fracture patterns. It can provide the surgeon with useful information for fracture analysis and may represent a good starting point for an automated system.

Background An intramedullary augmentation technique using a titanium cage with different types of hardware can be considered a new option in the management of proximal humeral fractures. This study aimed to report the perioperative, early, and late complications of proximal humeral fractures using the intramedullary augmentation technique. Methods From 2005 to 2017, 142 displaced proximal humeral fractures were treated in the same unit by the aforementioned technique. Perioperative, early, and late complications were evaluated in all patients. Clinical evaluation was performed according to the Constant and Disabilities of the Arm, Shoulder and Hand scores. Only 115 patient records could be considered to have long-term follow-up (7-12 years). Results Extra-articular migrations of K-wires, plate cutout, and screw penetration were not observed. A transitory axillary nerve palsy with inferior humeral head subluxation was observed in 41 patients (29.8%). Of the 142 patients, 2 (1.4%) manifested early signs of infection, and 1 underwent a reoperation after 30 days. Complete bone healing was obtained at a mean of 3.5 months in 140 of 142 shoulders (98.6%). We achieved long-term follow-up on only 115 patients because 14 had died, 6 lived abroad, and 7 could not participate due to illness. The results were good or excellent in 99 patients (86%), fair in 12 (10.4%), and poor in 4 (3.4%). K-wires were removed in 15 of 79 patients (11.5%). Nonunion or malunion occurred in 1 patient (0.8%). Asymptomatic avascular necrosis developed in 8 patients (6.9%) after 5 years, and secondary glenohumeral osteoarthritis occurred in 6 (5.2%). Conclusions Intraoperative and postoperative analyses with short-, medium-, and long-term outcomes show that the intramedullary augmentation technique improves fracture treatment with significantly good anatomic reconstruction in complex and unstable cases. The bone healing rate is significantly high, and the technique is associated with a significantly low percentage of complications.

Background Several hematological indices including subtypes of leukocytes populations have been associated with cardiovascular outcome. Takotsubo syndrome (TTS) is a form of acute heart failure syndrome featured by several in‐hospital complications (IHCs). Hypothesis Hematological indices at admission may predict IHCs in TTS patients. Methods One hundred and sixty consecutive patients with TTS were enrolled in a multicenter prospective registry. Clinical data, admission hemogram, and IHCs were recorded. Results Incidence of IHCs was 37%, including pulmonary edema 9%, cardiogenic shock 9%, need of invasive ventilation 10%, death 8%, stroke 2.5%, and left ventricular thrombi 6%. Patients with IHCs were older, more frequently male, with physical stressor‐induced TTS, lower left ventricular ejection fraction at admission. Neutrophil/lymphocyte ratio (NLr) (12 ± 12 vs 7 ± 8, P = .002) and white blood cells/mean platelet volume ratio (1.2 ± 0.5 vs 1.0 ± 0.5, P = .03) at admission were significantly higher in patients with IHCs. NLr values were predictor of IHCs (Odds ratios [OR] 1.07, 95% CI 1.03‐1.11, P

Background: The short- and long-term prognosis of Takotsubo syndrome (TTS) presenting with right ventricular (RV) involvement remains poorly understood. Research Question: What is the incidence and clinical outcome of RV involvement in TTS? Study Design and Methods: This study analyzed 839 consecutive patients with TTS (758 female subjects and 81 male subjects) in a multicenter registry. RV involvement was defined as wall motion abnormality of the RV free wall, with or without apical involvement. The median long-term follow-up was 2.1 years (interquartile range, 0.3-4.5 years). The primary outcome was in-hospital and out-of-hospital all-cause mortality. The secondary end point was a composite of in-hospital death, thromboembolic events, cardiogenic shock, pulmonary edema, and malignant arrhythmias. Results: The incidence of RV involvement in TTS was 11% (n = 93). More often patients with RV involvement were male compared with patients without RV involvement (P = .02). There was a slight difference in the left ventricular ejection fraction measured in patients with RV involvement vs those patients with isolated left ventricular TTS (38 ± 10% vs 40 ± 10%; P = .03). No major differences in terms of comorbidities were observed between groups except regarding a history of cancer, which was significantly more prevalent in patients with TTS presenting with RV involvement (P = .03). Physical stressors were more prevalent in the RV group (P < .01), whereas emotional stressors were less prevalent (P < .01). Patients with RV involvement had a higher incidence of in-hospital cardiogenic shock (P = .02). The primary outcome (in- and out-of-hospital all-cause mortality) was observed in 12.8% of patients without RV involvement compared with 29% of patients with RV involvement. Although the in-hospital mortality rate was similar in both groups, a higher out-of-hospital all-cause mortality rate (log-rank test, P = .008) was observed in the RV involvement group. The Cox multivariable regression analysis showed that physical triggers were independent predictors of RV involvement. Interpretation: RV involvement defines a high-risk cohort of patients with TTS. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT04361994; URL: www.clinicaltrials.gov.

Purpose: To evaluate the clinical and radiologic outcomes of patients undergoing arthroscopic glenoid bone allograft combined with subscapularis upper-third tenodesis for anterior shoulder instability associated with clinically relevant bone loss and hyperlaxity. Methods: Between January 2016 and December 2017, patients with recurrent anterior shoulder instability associated with bone loss and hyperlaxity were selected and treated with arthroscopic iliac crest bone graft combined with subscapularis upper-third tenodesis. The selection criteria were as follows: more than 5 dislocations; positive apprehension, anterior drawer, and Coudane-Walch test results; glenoid bone defect between 15% and 30% and humeral bone defect with an engaging Hill-Sachs lesion; and no previous shoulder surgery. All patients were followed up with the Constant score, University of California-Los Angeles (UCLA) rating, Rowe score, and visual analog scale evaluation. Assessments were performed with plain radiographs and a PICO computed tomography scan before surgery and at 2 years of follow-up. Results: Nineteen patients were included in the study, with a mean follow-up duration of 34.6 months (range, 24-48 months). In 17 patients (89%), excellent clinical results were recorded according to the Rowe score. The Constant score improved from 82.9 (standard deviation [SD], 5.2) to 88.9 (SD, 4.3) (P = .002); Rowe score, from 25.3 (SD, 5.3) to 89.1 (SD, 21.8) (P < .001); UCLA score, from 23.7 (SD, 3) to 31.5 (SD, 4.8) (P < .001); and visual analog scale score, from 3.2 to 1.3 (P < .001). Patients met the minimal clinically important difference 94.7%, 89.5%, and 47.3% of the time for the Rowe score, UCLA score, and Constant score, respectively. Bone graft resorption was observed in all patients: partial in 9 and complete in 10. We recorded 2 recurrent traumatic dislocations (11%), with no case of persistent anterior apprehension or other complication. Conclusions: An arthroscopic glenoid bone graft combined with subscapularis upper-third tenodesis may be a valid surgical option to treat recurrent anterior instability associated with both bone loss and hyperlaxity. Level of evidence: Level IV, case series.

Background/Aims: Cherry angiomas (CAs) are one of the most common vascular manifestations of the skin. By and large, these benign lesions often only represent an aesthetic problem. In the literature, few authors have focused on the pathogenesis of these lesions, and some risk factors have been identified, such as the presence of cutaneous and nonskin neoplasias. In this study, the correlation between the distribution of CAs and breast cancer was investigated. Methods: We carried out a study whereby 50 women with unilateral breast cancer and the presence of CAs on the anterior thoracic wall were evaluated, with a particular focus on the difference in the number of CAs between the two haemithoraces. The data was elaborated using the Wilcoxon signed-rank test in order to evaluate whether there was a statistical significance in the distribution of CAs. Results: In 31 patients we found that the number of CAs was greater on the cancerous breast than on the contralateral one (p value

During COVID-19 pandemic, older adults are the segment of the population at higher health risk. Given the important role the risk perception has in influencing both the behaviors and psychological well-being, it appears useful exploring this factor in this segment of the population. Despite different studies already described the factors influencing the risk perception, few focused on older adults. For this reason, we investigated risk perception in 514 people over 60 years during the lockdown. We administered a structured interview collecting socio-demographic information, sources of information used, actions undertaken to avoid contagion, and risk perception. Risk perception related to COVID-19 was significantly lower than the perceived risk associated with other threats, and it was correlated to the number of sources of information used but not to the actions undertaken. Furthermore, we found higher risk perception in who knew infected persons, and a negative correlation between the risk perception and age, with the over 75 perceiving a lower risk of getting infected compared to the younger participants. Our results should be taken as informative for future studies. Indeed, further studies on the older adults and the risk perception during emergencies are needed to better orient both communication and supporting strategies.

Headache disorders are prevalent and disabling conditions impacting on people of all ages, including children and adolescents with substantial impact on their school activities and leisure time. Our study aims to report specific information on headaches in children and adolescents based on the Global Burden of Disease (GBD) study, that provides estimates for incidence, prevalence, fatal and non-fatal outcomes. We relied on 2007 and 2017 GBD estimates for prevalence and Years Lived with Disability (YLDs) at the global level and in WHO regions. The results show that, migraine and tension-type headache (TTH) together account for 37.5% of all-cause prevalence and for 7% of all-cause YLDs. Over the past decade, prevalence rates showed a mild increase of TTH in all ages and of migraine alone for adolescents. The YLDs increased among females of all ages with some regional differences that might be connected to the unequal availability of effective acute and prophylactic treatments across world regions. GBD data support the need to promote public health policies and strategies including diagnosis, pharmacological and non-pharmacological treatments that are expected to help reduce the disability and burden associated to migraine and TTH among children and adolescents.

Total Hip Arthroplasty (THA) has been defined the surgical procedure of the century considering its outcome and cost-benefit ratio (1). Both standard and robotic assisted procedures are increasing, thus, comparison between standard and robotic surgery become useful to understand the cost-benefit of the latter. The prerequisites of the robotic assisted arthroplasty are precision, accuracy, limitation of errors and safety but, on the other hand, its cost is the main drawback. The primary endpoint of our research was to evaluate differences in terms of blood transfusion rates between standard manual and robotic arm assisted THA. All the robotic procedures have been managed using semi active Robotic Arm interactive orthopaedic System (RIO® MAKO Stryker surgical corporation) in a group of patients who underwent primary uncemented total hip arthroplasty (THA) for osteoarthritis or avascular necrosis. Secondary endpoints were the evaluation of length of hospital stay (LOS), age category, gender and the impact of the learning curve on surgical time in the robotic surgery sample. Our retrospective cohort study was conducted between July 2014 and December 2018. Data have been collected from the Tuscany regional hospital discharge register, extracting the relative Hospital Discharge Forms (SDO). During the period of the study, 1537 patients underwent uncemented total hip arthroplasty for osteoarthritis or avascular necrosis. The sample was divided in two subgroups: 1142 patients (74.3%) operated on with standard manual technique and 395 patients (25.7%) operated on with Mako- Stryker Robotic System. In the descriptive analysis, the average values of age and days of hospitalization with 95% CI were calculated. Mean significance was assessed by the T student test. The association between surgical modality and gender was assessed with the chi-square test. The multivariate logistic regression model was used to evaluate the risk of transfusion (outcome variable), between conventional and robotic surgical techniques. The significance threshold was set up at p0.05. During the period of the study we observed a decrease in standard surgery and an increase in robotic surgery; an increasing number of women per year underwent total uncemented total hip arthroplasty. We found a statistical significance in favor of robotic procedures in terms of transfusion percentage (OR 6.10, 95% CI 2.96-12.59, p0,001), highlighting the greatest risk in women (OR 1.90, 95%CI 1.30-2.78, p=0.001 ), length of hospital stay (Mr=4.24, SD=2.04, 95% CI 4.04-4.44) (Ms=8.04, SD=2.84, 95%CI 7.88-8.21), (p0.01). Operative time in the robotic sample decreased substantially with the rise of surgical experience (106.75±13.4 mins in 2014; 82.79±15.95 mins in 2018) (p0.01). Since the Robotic procedure is a technologically demanding process, an adequate surgical learning curve is mandatory. Our paper, comparing conventional vs robotic assisted THA, showed in favor of the robotic one, a statistically significant reduction of number of transfusions (p0.001) and length of hospital stay (p0.01).

Background The degree to which work-related difficulties are recognized in headache research is poor and often carried out with inadequate information such as “reduced ability to work as usual”, which do not capture at all the variety of difficulties and the factors that impact over them. The aim of this paper is to present the validation of the HEADWORK questionnaire, which addresses the amount and severity of difficulties in work-related tasks and the factors that impact over them. Methods We developed a set of items based on a previous literature review and patients’ focus groups and tested it on a wide set of patients with episodic and chronic migraine attending eight different Italian headache centers. HEADWORK factor structure was assessed with exploratory and confirmatory factor analysis; internal consistency and construct validity were addressed as well. Results The validation sample (N = 373) was mostly composed of patients with episodic migraine without aura (64.3%) and of females (81%). Factor analysis retrieved two different scales: “Work-related difficulties”, composed of eleven items which explain 67.1% of the total variance, and “Factors contributing to work difficulties”, composed of six items which explain 52.1% of the total variance. Both HEADWORK subscales have good measurement properties, with higher scores being associated to higher disability, lower quality of life, lower productivity, higher headache frequency and pain intensity. Conclusions HEADWORK is a 17-item, two-scale questionnaire addressing the impact of migraine on work-related difficulties in terms of difficulties in general or specific skills, and the factors contributing to these difficulties, defined as negative impact on work tasks. It can be used to address disability weights for the purpose of calculating the burden of migraine, and to assess the balance between therapeutic and side effects of medication on productivity.

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IMPORTANCE Takotsubo syndrome (TTS) is an acute, reversible heart failure syndrome featured by significant rates of in-hospital complications. There is a lack of data for risk stratification during hospitalization. OBJECTIVE To derive a simple clinical score for risk prediction of in-hospital complications among patients with TTS. DESIGN, SETTING, AND PARTICIPANTS In this prognostic study, 1007 consecutive patients were enrolled in the German and Italian Stress Cardiomyopathy (GEIST) registry from July 1, 2007, through December 31, 2017, and identified as the derivation cohort; 946 patients were enrolled in the Spanish Registry for Takotsubo Cardiomyopathy (RETAKO) as the external score validation. An admission risk score was developed using a stepwise multivariable regression analysis from 2 registries. Data analysis was performed from March 1, 2018, through July 31, 2018. MAIN OUTCOMES AND MEASURES In-hospital complications were defined as death, pulmonary edema, need for invasive ventilation, and cardiogenic shock. Four variables were identified as independent predictors of in-hospital complications and were used for the score: male sex, history of neurologic disorder, right ventricular involvement, and left ventricular ejection fraction (LVEF). RESULTS Of the 1007 patients enrolled in the GEIST registry, 107 (10.6%) were male, with mean (SD) age of 69.8 (11.4) years. Overall rate of in-hospital complications was 23.3% (235 of 1007) (death, 4.0%; pulmonary edema, 5.8%; invasive ventilation, 6.4%; and cardiogenic shock, 9.1%). The GEIST prognosis score was derived by providing 20 points each for male sex and history of neurologic disorders and 30 points for right ventricular involvement and then subtracting the value in percent of LVEF (decimal values between 0.15 and 0.70). Score accuracy on area under the receiver operating characteristic curve analysis was 0.71, with a negative predictive power of 87% with scores less than 20. External validation in the RETAKO population (124 [13.1%] male; mean [SD] age, 69.5 [14.9] years) revealed an area under the curve of 0.73 (P = .46 vs GEIST derivation cohort). Stratification into 3 risk groups (40 points) classified 316 patients (40.9%) as having low risk; 342 (44.3%) as having intermediate risk, and 114 (14.8%) as having high risk of complications. The observed in-hospital complication rates were 12.7% for low-risk patients, 23.4% for intermediate-risk patients, and 58.8% for high-risk patients (P < .001 for trend). After 2.6 years of follow-up, patients with in-hospital complications had significantly higher rates of mortality than those without complications (40% vs 10%, P = .01). CONCLUSIONS AND RELEVANCE The GEIST prognostic score may be useful in early risk stratification for TTS. High-risk patients with TTS may require an intensive care unit stay, and low-risk patients with TTS could be discharged within a few days. In-hospital complications in patients with TTS may be associated with increased risk of long-term mortality.

Background Current literature only reports variable information from single‐center studies on the recurrence rate, the complications, and the outcome of patients with Takotsubo syndrome ( TTS) experiencing recurrent TTS . Therefore, a detailed description of clinical characteristics, predictors, and the prognostic impact of patients with TTS and recurrences in a multicenter registry is needed. Methods and Results We analyzed 749 patients with TTS from 9 European centers being part of the international, multicenter GEIST (German Italian Stress Cardiomyopathy) Registry. Patients were divided into the recurrence group and the nonrecurrence group. The recurrence rate at a median follow‐up of 830 days (interquartile range, 118–1701 days) was 4%. Most recurrences were documented in the first 5 years after the index TTS episode. Up to 2 TTS recurrences were documented in 2 of 30 patients (6%). A variable ballooning pattern (n=6, 0.8%) with, in particular, involvement of the right ventricular occurred in 3 cases (0.4%) at the recurrence event. Except for the higher presence of arterial hypertension (86.7% versus 68.3%; P =0.03) in the recurrence group, no other baseline characteristics were different between groups. Observation of TTS complications during follow‐up, including stroke, thromboembolic events, in‐hospital death, and cardiogenic shock, revealed no significant differences between groups ( P >0.05), except the higher presence of pulmonary edema in the recurrence group versus the nonrecurrence group (13.3% versus 4.9%; P =0.04). Conclusions The incidence of TTS recurrence is estimated to be 4% in this multicenter TTS registry. A variable TTS pattern at recurrence is common in up to 20% of recurrence cases.

The short- and long-term prognosis of Takotsubo syndrome (TTS) presenting with right ventricular (RV) involvement remains poorly understood.What is the incidence and clinical outcome of RV involvement in TTS?This study analyzed 839 consecutive patients with TTS (758 female subjects and 81 male subjects) in a multicenter registry. RV involvement was defined as wall motion abnormality of the RV free wall, with or without apical involvement. The median long-term follow-up was 2.1 years (interquartile range, 0.3-4.5 years). The primary outcome was in-hospital and out-of-hospital all-cause mortality. The secondary end point was a composite of in-hospital death, thromboembolic events, cardiogenic shock, pulmonary edema, and malignant arrhythmias.The incidence of RV involvement in TTS was 11% (n = 93). More often patients with RV involvement were male compared with patients without RV involvement (P = .02). There was a slight difference in the left ventricular ejection fraction measured in patients with RV involvement vs those patients with isolated left ventricular TTS (38 ± 10% vs 40 ± 10%; P = .03). No major differences in terms of comorbidities were observed between groups except regarding a history of cancer, which was significantly more prevalent in patients with TTS presenting with RV involvement (P = .03). Physical stressors were more prevalent in the RV group (P .01), whereas emotional stressors were less prevalent (P .01). Patients with RV involvement had a higher incidence of in-hospital cardiogenic shock (P = .02). The primary outcome (in- and out-of-hospital all-cause mortality) was observed in 12.8% of patients without RV involvement compared with 29% of patients with RV involvement. Although the in-hospital mortality rate was similar in both groups, a higher out-of-hospital all-cause mortality rate (log-rank test, P = .008) was observed in the RV involvement group. The Cox multivariable regression analysis showed that physical triggers were independent predictors of RV involvement.RV involvement defines a high-risk cohort of patients with TTS.ClinicalTrials.gov; No.: NCT04361994; URL: www.clinicaltrials.gov.

Background It is common clinical experience that, after structured withdrawal, some patients with chronic migraine and medication overuse headache (CM with MOH) are more prone than others to relapse and to be in need of further structured treatments. Our aim was to explore similarities and differences between frequent relapsers (FRs) and non-frequent relapsers (NFRs) by considering their point of view, perceptions, and perspective of their subjective experience with relapse into CM with MOH. Methods Patients were consecutively recruited on occasion of a structured withdrawal treatment and were interviewed individually about their headache experience and their perspectives on relapse into CM with MOH. We considered FR those patients requiring 2 or more structured withdrawals for MOH within 3 years. A narrative approach with no preconceived coding schemes was employed. To facilitate coding, categorization and organization of data the software QRS NVivo 11.0 was used: themes were defined as common to FR and NFR, or peculiar (by frequency or content) to one of the 2 groups. Results Sixteen patients (13 women; mean age of 53) were interviewed: 7 were classified as FRs. A total of 22 themes emerged from 552 single quotations (the 10 most relevant covered 82% of the entire body of quotations). Four themes were commonly reported by both FR and NFR patients, and 6 were peculiar to one group only. Common aspects included issues connected to the dilemma between disclosing, concealing and the feelings of isolation around MOH, the idea of being addicted to medication, presence of anxiety, and the attempt to use non-pharmacological therapies as an alternative to medication. Peculiar aspects included causal attribution (FRs attributed headache to uncontrollable factors); future expectations at the time point of withdrawal (FRs were generally resigned); high-performance functioning (FRs believed they are "forced" to reach high levels of performance as a consequence of others' inability); coping strategies (FRs tended to "passively accept" problems and showed avoidance-related behaviors). Moreover, FRs were less frequently aware of their problems and described more frequently depressive symptoms. Conclusions Our results highlight that some differences between FR and NFR patients with CM and MOH exist. Frequent relapsers among patients with CM and MOH reported some important peculiarities of the lived experience of having chronic migraine; clinicians should recognize these psychosocial aspects such as social relationships, future expectations, the experience of illness, medication management, and how the withdrawal experience is regarded, as they may be associated with frequent relapse into MOH.

Background This study regards a volumetric analysis of proximal humeral fractures. The main purpose was to investigate the head displacement in relation to the shaft and its link to volume reductions (“bone loss”) of the anatomic segments interposed between the head and the shaft: the tuberosities and the calcar. We call this area “control volume.” Methods In 20 fractures, we used 3-dimensional virtual reconstruction to create a reference system that divides geometrically the control volume and allows the evaluation of displacement angles of the humeral head. We calculated the volumetric reduction of control volume segments for each fracture through a specific mathematical protocol. Results The measurement of the head displacement angles in 20 fractures led to following results: in the coronal plane, 10 varus, 6 valgus, 4 neutral; in the sagittal plane, 6 anterior tilt, 9 posterior tilt, 5 neutral position. There was a reduction of control volume in 19 of 20 fractures. Only in 1 fracture was the control volume intact and the fracture was nonimpacted. In 19 impacted fractures, the volume reduction was variable (4% minimum loss, 98% maximum loss). In head varus position, loss was greater in the medial area than in the lateral area. There was generally a clear correspondence between the positions assumed by the head and the volumetric losses of the respective control volume segments. Conclusions The control volume is an important anatomic and functional area of the proximal humerus. A morphovolumetric 3-dimensional approach improves knowledge about pathomorphology of proximal humeral fractures.

Introduction: Myasthenia gravis (MG) is an autoimmune disease whose period of typical onset is around 20–40 years (i.e., early onset), thus in the peak of working age, or around 60–80 years (i.e., late onset). However, the information on work-related issues and employment status are sparse and not systematically reported. Therefore, we performed a systematic literature review with meta-analysis to address the employment status of MG patients. Methods: We searched for papers reporting employment status on participants with MG published between January 2000 and May 2019. Information on employment was extracted. Random-effects models were used to produce meta-analytic estimates for the proportion of employed patients. Results: In total, 1,045 records were retrieved, of which 19 fitted the inclusion criteria. In total, 3,600 participants (average age 47.5, range 35–60) were included in the studies and 1,579 of them were employed. The proportion of employed patients varied from 28 to 82%, with an extreme heterogeneity between studies. Overall, the pooled proportion of workers was 50% (95% CI 41–60%). Subgroup analyses suggested a possible, although not significant, higher proportion of workers among women, younger participants, those with a higher level of education, shorter MG duration, and less frequently thymectomized, whereas a lower proportion was observed among those with generalized, bulbar, and respiratory symptoms. Conclusions: The results of our meta-analysis show that the percentage of employment is considerably low if we take into account that the mean age of MG patients involved in the included studies was around 48 years, thus in peak of working life. Therefore, it is important to understand what kind of influence MG exerts on work dynamics.

Background Deep Brain Stimulation (DBS) is increasingly used in pediatric patients affected by isolated dystonia, with excellent results. Despite well documented long-term effects on motor functioning, information on quality of life and social adaptation is almost lacking. Objectives The present study aims to explore the experience of illness and the relation with the device in adult patients suffering from dystonia who underwent DBS surgery in pediatric age. Methods A narrative inquiry approach was used to collect patients’ narratives of their experience with dystonia and DBS stimulator. A written interview was administered to 8 patients over 18 years old with generalized isolated dystonia who had undergone pallidal DBS implantation in childhood. A thematic analysis was realized to examine the narratives collected. Results Five main themes emerged: “relationship with the disease”, “experience related to DBS procedure”, “relationship with one's own body”, “fears”, “thoughts about future”. Despite a general satisfaction in relation to DBS intervention, some patients expressed difficulties, such as the acceptance of changes in one's own body, concerns and fears regarding the device and the future, also considering the critical phase of transition from childhood to adulthood. Conclusions These results suggest that further research is needed to understand the contribution of psychological, as much as medical, aspects to the overall outcome of the intervention. The present explorative study encourages a deeper investigations of psychological aspects of patients, in order to plan a tailored care path and to decide whether to suggest a psychological support, both before and after the intervention.

Significant side effects or drug interactions can make pharmacological management of headache disorders very difficult. Non-conventional and non-pharmacological treatments are becoming increasingly used to overcome these issues. In particular, non-invasive neuromodulation, nutraceuticals, and behavioral approaches are well tolerated and indicated for specific patient categories such as adolescents and pregnant women. This paper aims to present the main approaches reported in the literature in the management of headache disorders. We therefore reviewed the available literature published between 2010 and 2020 and performed a narrative presentation for each of the three categories (non-invasive neuromodulation, nutraceuticals, and behavioral therapies). Regarding non-invasive neuromodulation, we selected transcranial magnetic stimulation, supraorbital nerve stimulation, transcranial direct current stimulation, non-invasive vagal nerve stimulation, and caloric vestibular stimulation. For nutraceuticals, we selected Feverfew, Butterbur, Riboflavin, Magnesium, and Coenzyme Q10. Finally, for behavioral approaches, we selected biofeedback, cognitive behavioral therapy, relaxation techniques, mindfulness-based therapy, and acceptance and commitment therapy. These approaches are increasingly seen as a valid treatment option in headache management, especially for patients with medication overuse or contraindications to drug treatment. However, further investigations are needed to consider the effectiveness of these approaches also with respect to the long-term effects.

A female patient with non-Hodgkin lymphoma who tested positive for surface antigen of the hepatitis B virus and negative for hepatitis B core antibody experienced a reactivation of occult HBV infection 20 months after rituximab discontinuation despite lamivudine prophylaxis covering the 4 months of rituximab administration and the subsequent 12 months. © 2012 Springer-Verlag.

Background Werner syndrome is a progeroid disorder characterized by premature age-related phenotypes. Although it is well established that autosomal recessive mutations in the WRN gene is responsible for Werner syndrome, the molecular alterations that lead to disease phenotype remain still unidentified. Results To address whether epigenetic changes can be associated with Werner syndrome phenotype, we analysed genome-wide DNA methylation profile using the Infinium MethylationEPIC BeadChip in the whole blood from three patients affected by Werner syndrome compared with three age- and sex-matched healthy controls. Hypermethylated probes were enriched in glycosphingolipid biosynthesis, FoxO signalling and insulin signalling pathways, while hypomethylated probes were enriched in PI3K-Akt signalling and focal adhesion pathways. Twenty-two out of 47 of the differentially methylated genes belonging to the enriched pathways resulted differentially expressed in a publicly available dataset on Werner syndrome fibroblasts. Interestingly, differentially methylated regions identified CERS1 and CERS3, two members of the ceramide synthase family. Moreover, we found differentially methylated probes within ITGA9 and ADAM12 genes, whose methylation is altered in systemic sclerosis, and within the PRDM8 gene, whose methylation is affected in dyskeratosis congenita and Down syndrome. Conclusions DNA methylation changes in the peripheral blood from Werner syndrome patients provide new insight in the pathogenesis of the disease, highlighting in some cases a functional correlation of gene expression and methylation status. Electronic supplementary material The online version of this article (doi:10.1186/s13148-017-0389-4) contains supplementary material, which is available to authorized users.

// Fabio Ciccarone 1,2 , Elisabetta Valentini 1,2 , Maria Giulia Bacalini 3 , Michele Zampieri 1,2 , Roberta Calabrese 1,2 , Tiziana Guastafierro 1,2 , Germano Mariano 1,2 , Anna Reale 1,2 , Claudio Franceschi 3 and Paola Caiafa 1,2 1 Department of Cellular Biotechnologies and Hematology, “Sapienza” University of Rome, Rome, Italy 2 Pasteur Institute-Fondazione Cenci Bolognetti, Rome, Italy 3 Department of Experimental Pathology, Alma Mater Studiorum, University of Bologna, Bologna, Italy Correspondence: Fabio Ciccarone, email: // Paola Caiafa, email: // Keywords : poly(ADP-ribosyl)ation, TET1, DNA methylation, 5-hydroxymethylcytosine Received : February 07, 2014 Accepted : April 16, 2014 Published : April 17, 2014 Abstract TET enzymes are the epigenetic factors involved in the formation of the sixth DNA base 5-hydroxymethylcytosine, whose deregulation has been associated with tumorigenesis. In particular, TET1 acts as tumor suppressor preventing cell proliferation and tumor metastasis and it has frequently been found down-regulated in cancer. Thus, considering the importance of a tight control of TET1 expression, the epigenetic mechanisms involved in the transcriptional regulation of TET1 gene are here investigated. The involvement of poly(ADP-ribosyl)ation in the control of DNA and histone methylation on TET1 gene was examined. PARP activity is able to positively regulate TET1 expressionmaintaining a permissive chromatin state characterized by DNA hypomethylation of TET1 CpG island as well as high levels of H3K4 trimethylation. These epigenetic modifications were affected by PAR depletion causing TET1 down-regulation and in turn reduced recruitment of TET1 protein on HOXA9 target gene. In conclusion, this work shows that PARP activity is a transcriptional regulator of TET1 gene through the control of epigenetic events and it suggests that deregulation of these mechanisms could account for TET1 repression in cancer.

Previous studies have reported slightly higher stroke rates in Takotsubo Syndrome compared to acute myocardial infarction. Our goal was to evaluate the temporal course of stroke rates and left ventricular recovery in patients with Takotsubo Syndrome.We retrospectively examined the clinical and imaging data of 72 patients with Takotsubo Syndrome. The data collected came from January 2005 to March 2017. Left ventricular performance was evaluated by cardiovascular magnetic resonance imaging (MRI) in all patients during the acute phase of Takotsubo Syndrome and in a follow-up scan 2 months later. Acute stroke and major adverse clinical events, such as myocardial infarction or recurrence of Takotsubo Syndrome and death, were also determined for each patient at 30 days and 12 months after initial presentation.The MRI scans performed during the acute phase of Takotsubo Syndrome demonstrated apical ballooning with anterior wall motion dysfunction in 65 (90%) patients. Imaging performed 2 months later demonstrated resolution of this in 97% of those patients. Median left ventricular ejection fraction also significantly increased between both scans (49.5% vs. 64.0%, P 0.001). We observed 9 (12%) events in the study population within 12 months of the initial diagnosis of Takotsubo Syndrome. Stroke had an event rate of 2.8% after 30 days and 4.2% after 12 months.Apical ballooning was found in the majority of our Takotsubo Syndrome patients on the MRI scans performed at presentation. This finding was subsequently associated with higher than expected stroke rates within 30 days of diagnosis and with rapid recovery of left ventricular function within 2 months of diagnosis. This suggests that rapid improvement in left ventricular morphology and function may facilitate the formation of cardiac emboli and consequently increase stroke rates in Takotsubo Syndrome. Although no guidelines currently exist for the treatment of Takotsubo Syndrome, these results may point to a potential role for temporary oral anticoagulation in high-risk patients. Future studies should examine if stroke rates after Takotsubo Syndrome have been underestimated.

Background: Research addressing the impact of a large number of factors on unemployment is scarce. We aimed to comprehensively identify factors related to unemployment in a sample of persons aged 18–64 from Finland, Poland and Spain. Methods: In this cross-sectional study, factors from different areas were considered: socio-demographic indicators, health habits, chronic conditions, health state markers, vision and hearing indicators, and social networks and built environment scores. Results: Complete data were available for 5003 participants, mean age 48.1 (SD 11.5), 45.4% males. The most important factors connected to unemployment were health status indicators such as physical disability (OR = 2.944), self-rated health (OR = 2.629), inpatient care (OR = 1.980), and difficulties with getting to the toilet (OR = 2.040), while the most relevant factor related to employment were moderate alcohol consumption (OR = 0.732 for non-heavy drinkers; OR = 0.573 for infrequent heavy drinkers), and being married (OR = 0.734), or having been married (OR = 0.584). Other factors that played a significant role included presence of depression (OR = 1.384) and difficulties with near vision (OR = 1.584) and conversation hearing (OR = 1.597). Conclusions: Our results highlight the importance of selected factors related to unemployment, and suggest public health indications that could support concrete actions on modifiable factors, such as those aimed to promote physical activity and healthy behaviors, tackling depression or promoting education, in particular for the younger.

Background and aims Systemic inflammatory activation can be observed in both Takotsubo cardiomyopathy (TTC) and acute coronary syndrome (ACS). The aim of this study was therefore to compare circulating cytokine levels during the acute and subacute phase of TTC and ACS. Methods One hundred thirty-six consecutive patients were enrolled in the study; after a propensity score matching, 32 TTC patients were compared with 32 subjects with ACS. Clinical baseline features and circulating levels of interleukin(IL)-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-γ, MCP1, EGF, VEGF, TNFα were obtained at admission (t0) and after 120 h (t1). Results At t0, several circulating IL levels were higher in subjects with TTC (IL-2 2 vs. 0.5 pg/ml, IL-4 1.5 vs. 0.82 pg/ml, IL-10 3.34 vs. 1.62 pg/ml, TNF-α 5 vs. 2.3 pg/ml, IFN-γ 0.92 vs. 0.32 pg/ml, EGF 84.8 vs. 10.7 pg/ml, p At t1, IL-2 and EGF levels were still higher in patients with TTC vs. those with ACS (IL-2 4.6 vs. 0.72 pg/ml, p = 0.01; EGF 36.3 vs. 18.5 pg/ml, p = 0.03), while IL-6 serum levels were higher in ACS patients (19.6 vs. 7.35 pg/ml, p = 0.02). Conclusions Different inflammatory patterns can be observed during the acute and subacute phase of TTC when compared to ACS. Increased levels of anti-inflammatory interleukins can be found during the acute phase of TTC while ACS is featured by higher levels of IL-6 during the acute and sub-acute phase.

BACKGROUND: Persistent ST‐segment elevation in acute coronary syndrome is associated with both short and long‐term complications. By contrast, there is limited information about ST‐elevation and its evolution during takotsubo (stress) cardiomyopathy (TTC). AIM: To evaluate whether persistent downsloping ST‐elevation in the early stages of TTC might correlate with short and long‐term clinical events. METHODS: One‐hundred fifty‐eight consecutive subjects with TTC were prospectively enrolled and assessed by electrocardiogram. Patients were classified in two groups according to the presence of downsloping ST‐elevation ≥5 mm lasting at least 24 hr (“lambda‐wave” ST‐elevation group vs. without downsloping ST‐elevation) in at least one/two contiguous leads. RESULTS: Five (3.2%) patients, all female with a mean left ventricular ejection fraction 32 ± 5%, were included in the lambda‐wave ST‐elevation group. These patients were characterized by a higher prevalence of physical stressor (100% vs. 49%, p = 0.04) and higher admission and peak levels of troponin‐I levels during hospitalization. Peak of ST‐elevation in the lambda‐wave ST‐elevation group was reached 6 hr after admission and gradually decreased after 24 hr. In‐hospital complications were observed in all the patients presenting lambda ST‐elevation (100% vs. 23%, p = 0.03, OR: 29.1, p = 0.04); one patient presented endoventricular thrombosis and two died of cardiogenic shock. At long‐term follow‐up (mean 443 days), adverse events were observed in 80% of patients with lambda‐wave ST‐elevation (RR of adverse events at follow‐up 32, p

Background Left ventricular ( LV ) thrombi during Takotsubo syndrome represent a potential complication and can be associated with cerebrovascular embolic events. The aim of this study was to evaluate the exact incidence, predictors, and management strategies of LV thrombi in patients with Takotsubo syndrome. Methods and Results We enrolled 541 consecutive patients in a multicenter international registry. Clinical features and echocardiographic data at admission, during hospitalization, and after 3 months were evaluated. Survival rates for long‐term follow‐up (mean 984±908 days) were recorded. Twelve Takotsubo syndrome patients (2.2%) developed LV thrombi (all female presenting with apical ballooning pattern). All patients with LV thrombi were treated with oral anticoagulation therapy; however, 2 (17%) had a stroke before treatment initiation. These patients were characterized by a higher prevalence of ST ‐elevation (56% versus 16%; P P =0.001) as compared with those without LV thrombi. At multivariate analysis including age, sex, LV ejection fraction, ST ‐elevation at admission, and apical ballooning pattern, troponin I level >10 ng/mL was the only predictor for LV thrombosis (hazard ratio 6.6, confidence interval, 1.01–40.0; P =0.04). After 3 months all LV thrombi disappeared. Oral anticoagulation therapy was interrupted in all patients except 1. At long‐term follow‐up, the survival rate was not different between patients with and without LV thrombi (84% versus 85%; P =0.99). Conclusions LV thrombi have a relatively low incidence among patients with Takotsubo syndrome and were detected in female patients with apical ballooning pattern and increased troponin levels. Oral anticoagulation therapy for 3 months seems reasonable in these high‐risk patients.

Aging is associated with alterations in the content and patterns of DNA methylation virtually throughout the entire human lifespan. Reasons for these variations are not well understood. However, several lines of evidence suggest that the epigenetic instability in aging may be traced back to the alteration of the expression of DNA methyltransferases. Here, the association of the expression of DNA methyltransferases DNMT1 and DNMT3B with age has been analysed in the context of the MARK-AGE study, a large-scale cross-sectional study of the European general population. Using peripheral blood mononuclear cells, we assessed the variation of DNMT1 and DNMT3B gene expression in more than two thousand age-stratified women and men (35-75 years) recruited across eight European countries. Significant age-related changes were detected for both transcripts. The level of DNMT1 gradually dropped with aging but this was only observed up to the age of 64 years. By contrast, the expression of DNMT3B decreased linearly with increasing age and this association was particularly evident in females. We next attempted to trace the age-related changes of both transcripts to the influence of different variables that have an impact on changes of their expression in the population, including demographics, dietary and health habits, and clinical parameters. Our results indicate that age affects the expression of DNMT1 and DNMT3B as an almost independent variable in respect of all other variables evaluated. published

Gradual changes in the DNA methylation landscape occur throughout aging virtually in all human tissues. A widespread reduction of 5-methylcytosine (5mC), associated with highly reproducible site-specific hypermethylation, characterizes the genome in aging. Therefore, an equilibrium seems to exist between general and directional deregulating events concerning DNA methylation controllers, which may underpin the age-related epigenetic changes. In this context, 5mC-hydroxylases (TET enzymes) are new potential players. In fact, TETs catalyze the stepwise oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), driving the DNA demethylation process based on thymine DNA glycosylase (TDG)-mediated DNA repair pathway. The present paper reports the expression of DNA hydroxymethylation components, the levels of 5hmC and of its derivatives in peripheral blood mononuclear cells of age-stratified donors recruited in several European countries in the context of the EU Project 'MARK-AGE'. The results provide evidence for an age-related decline of TET1, TET3 and TDG gene expression along with a decrease of 5hmC and an accumulation of 5caC. These associations were independent of confounding variables, including recruitment center, gender and leukocyte composition. The observed impairment of 5hmC-mediated DNA demethylation pathway in blood cells may lead to aberrant transcriptional programs in the elderly. published

Takotsubo syndrome (TTS), a form of acute transient heart failure, has been associated with severe complications and considerable mortality rates. N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) might serve as a marker to identify high-risk patients but has not yet been investigated regarding prognostic implications in TTS. Aim of this study was to determine the short- and long-term prognostic utility of NT-proBNP in patients with TTS. The predictive value of admission NT-proBNP was assessed in an international, multicenter study including 177 consecutive TTS patients. Predefined endpoints were 30-day major adverse cardiac events (MACE) consisting of all-cause death, cardiogenic shock, and pulmonary edema as well as long-term mortality in median 2.3 years after the acute event. Stratification according to median admission NT-proBNP (4511 pg/ml) resulted in significantly higher 30-day MACE [22.5 versus 9.1%; odds ratio (OR) 2.90, 95% confidence interval (CI) 1.20–6.99 p = 0.015] and long-term mortality rates [16.3 versus 9.4%; hazard ratio (HR) 2.72, 95% CI 1.13–6.56 p = 0.021] in patients > median. The best admission NT-proBNP cutoffs to predict 30-day MACE and long-term mortality were determined at 5560 and 8178 pg/ml respectively, with subsequent improved risk stratification for short-term MACE (OR 3.61, 95% CI 1.49–8.72; p = 0.003) and long-term mortality (HR 4.40; 95% CI 1.85–10.44, p

Takotsubo syndrome (TTS) is associated with a considerable risk of complications during the acute phase and substantial long-term mortality rates. Concomitant atrial fibrillation may have an impact on outcome in these patients. Aim of this study was to assess the prevalence and prognostic relevance of atrial fibrillation in TTS.We performed an international, multicenter study including 387 TTS patients consecutively enrolled at 3 centers. Atrial fibrillation was defined as known history before admission or documented episodes during hospital stay. Long-term mortality was evaluated in median 2.9years after the acute event.Atrial fibrillation was found in 97 TTS patients (25.1%) and was associated with older age (p0.01), less emotional triggers (p=0.03), higher incidence of cardiogenic shock (p0.01), lower left ventricular ejection fraction (p0.01), and a prolonged hospital stay (p0.01). Determinants of atrial fibrillation at admission (n=34 patients; 9.0%) in multivariate logistic regression analysis were age (p=0.001) and cardiogenic shock (p=0.013). Long-term mortality was significantly higher in TTS patients with as compared to patients without atrial fibrillation (35.2% versus 15.3%; hazard ratio 3.02, 95% confidence interval 1.90-4.78; p0.001). In multivariate Cox regression analysis atrial fibrillation was identified as an independent determinant of outcome even after adjustment for clinical variables, left ventricular functional parameters (ballooning pattern, ejection fraction), and cardiogenic shock.In TTS patients, atrial fibrillation is frequent and associated with increased long-term mortality rates. Furthermore, our study identifies atrial fibrillation as an independent predictor of outcome and a potential tool for risk stratification in TTS.

The numb chin syndrome (NCS) is characterized by facial numbness along the distribution of the mental branch of the trigeminal nerve. Most cases of this syndrome that are not dental in origin have been associated with malignant tumors or diffuse metastatic disease, particularly with underlying lymphoproliferative diseases and breast cancer. NCS can appear together with other signs of neoplastic dissemination or constitute the presenting symptom of the disease. The appearance of this mental nerve neuropathy should be considered as a significant symptom for clinicians, and investigations to detect a possible cancer should be mandatory. We report 12 patients with the NCS as the presenting and isolated symptom of a generalized malignancy.

A serum multiple monoclonal component (MC) is very rare. We here report 6 patients with 3 MCs. The triple MC was detected in all of them by immunofixation. 2/6 patients did not present hematological or oncological associated disease, while in the remaining 4, Waldenstrom macroglobulinaemia (2 cases), Polycythemia Vera and non-Hodgkin lymphoma were diagnosed. Of the 49 global patients reported in the literature (6 + 43), 64.6% had a lymphoproliferative disorder and only in 3 cases there was no associated disease. Therefore, the detection of such laboratory evidence should propel physicians to a deeper investigation.

Cancer patients are more at risk of being unemployed or having difficulties to return to work (RTW) compared to individuals without health concerns, and is thus a major public health issue. The aim of this systematic review is to identify and describe the interventions developed specifically to help cancer patients to RTW after treatment. Two researchers independently screened the articles for inclusion and Critical Appraisal Skills Program (CASP) checklists were used to assess the methodology of the included studies. Ten manuscripts met the inclusion criteria. The type of studies were three quasi-experimental studies, three longitudinal studies, three randomized controlled trials (RCTs) and a qualitative study. RTW interventions were conducted in or outside the hospital (n = 6 and 3 respectively), or both (n = 1). Improvements in RTW were only observed in quasi-experimental studies. No improvement in RTW was noted in RCTs, nor in other measures (e.g., quality of life, fatigue). Lack of statistically significant improvement does not necessarily reflect reality, but may be attributed to non-adapted research methods. This systematic review underscores the need for researches in the RTW field to reach a consensus on RTW criteria and their assessment. Recommendations to this effect are suggested.

Background: Increased plasma levels of fibrinogen are been associated with an increased risk of cardiovascular accident. We aimed at verifying whether the changes of fibrinogen levels are associated with red blood cell (and/or hemoglobin) concentration. Methods: A group of 381 carefully selected healthy volunteers (219 male and 162 female), aged from 18 to 101 years, were enrolled in this study. Fasting blood samples were taken and all measurements (fibrinogen plasma level, whole blood viscosity, hemoglobin concentration, hematocrit value, red blood cell and white blood cell count, platelet count, glucose, total cholesterol and triglycerides plasma concentration, and C-reactive protein level) were obtained with standardized methodology using appropriate equipment, procedures, and controls. Results and Conclusions: In the male but not in the female group, plasma fibrinogen concentration inversely correlated with hemoglobin (P * 0.0001) and hematocrit value (P * 0.01). In a post hoc analysis, plasma fibrinogen level inversely correlated with hemoglobin in the subgroup of the 93 premenopausal women and directly correlated with age and inversely correlated with platelet count in the subgroup of the 69 postmenopausal women. Results of multiple regression analysis revealed that in all the subjects, except in the postmenopausal women, hemoglobin level is an independent predictor of fibrinogen plasma level. Considering the physiopathologic role of increased plasma fibrinogen concentration and the scarcity of pharmacologic approaches to decrease its level, these findings could be important in designing a preventive therapy of cardiovascular disease

PLoS one 10(1), 1-17 (2015). doi:10.1371/journal.pone.0116468, Published by PLoS, Lawrence, Kan.

Aims To evaluate changes in Hepatitis C Virus (HCV) RNA both in plasma and Peripheral Blood Mononuclear Cells (PBMC) in onco-haematological patients. Patients and methods 8 consecutive anti-HCV/HCV RNA-positive patients with onco-haematological diseases (5 with B-cell Non-Hodgkin Lymphoma and 3 with chronic lymphocytic leukaemia) were observed during chemotherapy and after its discontinuation. All were naive to chemotherapy. HCV RNA was sought by Real Time Polymerase Chain Reaction in Light Cycler 1.5 in plasma and PBMC samples collected before, during and after chemotherapy. Results An increase in HCV RNA of at least 1.5 log IU/mL in plasma and 1.1 log IU/ml in PBMC was observed in all 7 patients undergoing Rituximab-based chemotherapy; these patients showed a hepatic flare after discontinuation, life-threatening in one with cirrhosis. Also the 8th patient had cirrhosis, but was treated with Rituximab-sparing chemotherapy and did not show any increase in HCV RNA or a hepatic flare. Conclusion Rituximab-based chemotherapy favours an increase in HCV RNA in onco-haematological patients; this is followed by a hepatic flare, possibly immune-mediated and life threatening in cirrhotic patients.

The aim of the study was to evaluate clinical and virological differences in HBV reactivation between patients with overt and occult HBV infection. Twenty-three consecutive patients with symptomatic HBV reactivation occurring during or after immunosuppressive therapy were enrolled in a retrospective study: 10 with reactivation of overt HBV infection (overt group) and 13 of occult HBV infection (occult group). Twenty-one patients were treated with nucleot(s)ide analogues after HBV reactivation. Regimens including rituximab or fludarabine were administered more frequently in the occult group (61% vs. 31%, respectively). HBV reactivation was severe frequently in the overt (40%) and occult groups (38.4%). Patients in the overt group showed higher HBV-DNA titers (1.1×10 8±1.4×10 8 vs. 5.1×10 5±6.8×10 5IU; P

Autologous fat grafting procedures in plastic surgery have been extensively used to reinforce soft tissue in congenital or acquired tissue impairments. With this background, the aim of this study is firstly to examine the impact of a selective centrifugation on existing adipose stem cells (ASCs) in terms of stemness profile maintenance and, secondly, to investigate the effect of restoring volume in reconstruction on patients affected by soft tissue damage. After centrifugation, the fat graft products were separated into two layers and subsequently examined in vitro for the expression of CD34, CD90, CD117, CD105, CD29, CD31, CD44, CD73, CD133, CD14 and CD45 markers by flow cytometry and gene expression analyses were performed for Sox2, WNT3A, END, CD44, FUT4, COLL1, CTNNB1, hbEGF, KRTLG, MMP2 and VIM genes. The results showed that in the middle-high density (MHD) layer there was a peak concentration of ASCs, compared to another layer obtained after centrifugation. Research carried out on patients under treatment for soft tissue regeneration using cells obtained from MHD layer selection will be fundamental in comparative analysis. These studies will lead to an adequate standardization of outcomes, provided that treatment is performed through cell selection. Therefore, a unique procedure in tissue reconstruction and regeneration through fat grafting is presented here. Autologous fat grafting procedures in plastic surgery have been extensively used to reinforce soft tissue in congenital or acquired tissue impairments. With this background, the aim of this study is firstly to examine the impact of a selective centrifugation on existing adipose stem cells (ASCs) in terms of stemness profile maintenance and, secondly, to investigate the effect of restoring volume in reconstruction on patients affected by soft tissue damage. After centrifugation, the fat graft products were separated into two layers and subsequently examined in vitro for the expression of CD34, CD90, CD117, CD105, CD29, CD31, CD44, CD73, CD133, CD14 and CD45 markers by flow cytometry and gene expression analyses were performed for Sox2, WNT3A, END, CD44, FUT4, COLL1, CTNNB1, hbEGF, KRTLG, MMP2 and VIM genes. The results showed that in the middle-high density (MHD) layer there was a peak concentration of ASCs, compared to another layer obtained after centrifugation. Research carried out on patients under treatment for soft tissue regeneration using cells obtained from MHD layer selection will be fundamental in comparative analysis. These studies will lead to an adequate standardization of outcomes, provided that treatment is performed through cell selection. Therefore, a unique procedure in tissue reconstruction and regeneration through fat grafting is presented here.

International audience; Aberrant DNA methylation can lead to genome destabilization and to deregulated gene expression. Recently, 5-hydroxymethylcytosine (5hmC), derived from oxidation of 5-methylcytosine (5mC) by the Ten-Eleven Translo-cation (TET) enzymes, has been detected. 5hmC is now considered as a new epigenetic DNA modification with relevant roles in cell homeostasis regulating DNA demethylation and transcription. Our aim was to investigate possible changes in the DNA methylation/demethylation machinery in MS. We assessed the expression of enzymes involved in DNA methylation/demethylation in peripheral blood mononuclear cells (PBMCs) from 40 subjects with MS and 40 matched healthy controls. We performed also, DNA methylation analysis of specific promoters and analysis of global levels of 5mC and 5hmC. We show that TET2 and DNMT1 expression is significantly down-regulated in MS PBMCs and it is associated with aberrant methylation of their promoters. Furthermore , 5hmC is decreased in MS PBMCs, probably as a result of the diminished TET2 level.

A double monoclonal component (MC) detected in the serum and/or urine represents a very rare occurrence (2-6% of monoclonal gammopathies). In this study, we report 34 patients with double serum MCs, focusing on the associated diseases. The diagnosis was made using high-resolution serum protein electrophoresis and immunofixation. Of the 1214 patients with monoclonal gammopathies, 49 had a double MC but only 34 (2.8%) were included in our study. A double MC was associated with hematological malignancies in 20/34 cases. Based on our experience, a double MC is more often associated with other diseases, especially an oncohematological one.

Primary lymphoma of the female genital tract is very rare. We report the case of a 36-year-old woman who was referred to our hospital because of an indeterminate Pap smear test. The colposcopy showed a thickening of the posterior vaginal wall and various irregular ulcerated nodular lesions. Histological examination, immunohistochemistry and the staging procedures were conclusive of diffuse large B-cell lymphoma of the vagina, stage IEA. Complete remission was achieved after 6 cycles of immunopolychemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). No relapse has occurred during a follow-up of 71 months. Moreover, we reviewed the 62 previously reported cases of primary extranodal non-Hodgkin’s lymphoma of the vagina, focusing on clinicopathological and therapeutic aspects, to better characterize this unusual disease.

The aim of our study was to evaluate the presence of occult HCV infection in two settings of patients experiencing immunosuppression: patients with Human Immunodeficiency Virus (HIV) infection and those with onco-haematological disease. Sixty consecutive HIV-positive/anti-HCV-negative/HCV RNA-negative patients (HIV group) and 32 consecutive anti-HCV/HCV RNA negative patients with an onco-haematological disease first undergoing chemotherapy (Onco-haematological group) were enrolled. HCV-RNA was sought by real time RT-PCR in plasma and Peripheral Blood Mononuclear Cell (PBMC) samples obtained at enrolment and during follow-up, in the patients in the HIV group every three months and in those in the onco-haematological group at months 1 and 3 during chemotherapy and then every three months after treatment discontinuation. No plasma or PBMC sample collected at enrolment and during the follow-up in the HIV and onco-haematological groups was HCV RNA positive. The results of this study rule out the existence of occult HCV infection in patients with strong immunosuppression due to different conditions, HIV infection and onco-haematological diseases.

Background: Peptidylarginine deiminase 2 (PAD2) and peptidylarginine deiminase 4 (PAD4) are two members of PAD family which are over-expressed in the multiple sclerosis (MS) brain. Through its enzymatic activity PAD2 converts myelin basic protein (MBP) arginines into citrullines – an event that may favour autoimmunity – while peptidylarginine deiminase 4 (PAD4) is involved in chromatin remodelling. Objectives: Our aim was to verify whether an altered epigenetic control of PAD2, as already shown in the MS brain, can be observed in peripheral blood mononuclear cells (PBMCs) of patients with MS since some of these cells also synthesize MBP. Methods: The expression of most suitable reference genes and of PAD2 and PAD4 was assessed by qPCR. Analysis of DNA methylation was performed by bisulfite method. Results: The comparison of PAD2 expression level in PBMCs from patients with MS vs. healthy donors showed that, as well as in the white matter of MS patients, the enzyme is significantly upregulated in affected subjects. Methylation pattern analysis of a CpG island located in the PAD2 promoter showed that over-expression is associated with promoter demethylation. Conclusion: Defective regulation of PAD2 in the periphery, without the immunological shelter of the blood–brain barrier, may contribute to the development of the autoimmune responses in MS.

A 56-year-old woman presented with dyspnea and a large swelling in the upper vestibular region (Figure 1 A), appeared 6 weeks before and continuing to grow up. Physical examination suggested pleural effusion, subsequently confirmed by chest X-ray (Figure 1 B). Complete blood cell count and biochemistry values were all within normal ranges, excepting for LDH (2620 IU/L) and β(2) -microglobulin (9.4 mg/L).