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The purpose of this preclinical study was to evaluate the influence of tamoxifen (TAM) on the peri-implant bone remodeling of osseointegrated titanium implants in ovariectomized female rats.Seventy-two female rats underwent bilateral ovariectomy 20 weeks before implants placement. One titanium implant was inserted in each tibia of the animals. Six weeks following the implant surgery, animals were randomly divided into two experimental groups (n = 36), which received either saline solution (SS) or tamoxifen citrate (TAM) via gavage until euthanasia. Euthanasia was performed at 30, 60, and 90 days after the first gavage. Assessments of bone to implant contact (BIC), bone ingrowth percentage (BIN), morphological description of cellular and tissue reactions, immunohistochemistry for the detection of bone morphogenetic protein 2/4 (BMP2/4), runt-related transcription factor 2 (RUNX-2), osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP), and bone chemical composition through scanning electron microscopy with energy-dispersive x-ray spectroscopy were performed.Tamoxifen group presented higher BIC, higher BIN, higher RUNX-2 and OCN, lower TRAP-positive cells/mmTamoxifen enhanced the remodeling of the bone surrounding titanium implants in ovariectomized rats.

Background: TEXTMEDS (Text Messages to Improve Medication Adherence and Secondary Prevention After Acute Coronary Syndrome) examined the effects of text message–delivered cardiac education and support on medication adherence after an acute coronary syndrome. Methods: TEXTMEDS was a single-blind, multicenter, randomized controlled trial of patients after acute coronary syndrome. The control group received usual care (secondary prevention as determined by the treating clinician); the intervention group also received multiple motivational and supportive weekly text messages on medications and healthy lifestyle with the opportunity for 2-way communication (text or telephone). The primary end point of self-reported medication adherence was the percentage of patients who were adherent, defined as >80% adherence to each of up to 5 indicated cardioprotective medications, at both 6 and 12 months. Results: A total of 1424 patients (mean age, 58 years [SD, 11]; 79% male) were randomized from 18 Australian public teaching hospitals. There was no significant difference in the primary end point of self-reported medication adherence between the intervention and control groups (relative risk, 0.93 [95% CI, 0.84–1.03]; P =0.15). There was no difference between intervention and control groups at 12 months in adherence to individual medications (aspirin, 96% vs 96%; β-blocker, 84% vs 84%; angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, 77% vs 80%; statin, 95% vs 95%; second antiplatelet, 84% vs 84% [all P >0.05]), systolic blood pressure (130 vs 129 mm Hg; P =0.26), low-density lipoprotein cholesterol (2.0 vs 1.9 mmol/L; P =0.34), smoking ( P =0.59), or exercising regularly (71% vs 68%; P =0.52). There were small differences in lifestyle risk factors in favor of intervention on body mass index 2 (21% vs 18%; P =0.01), eating ≥5 servings per day of vegetables (9% vs 5%; P =0.03), and eating ≥2 servings per day of fruit (44% vs 39%; P =0.01). Conclusions: A text message–based program had no effect on medical adherence but small effects on lifestyle risk factors. Registration: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364448 ; Unique identifier: ANZCTR ACTRN12613000793718.

Background PReferentially expressed Antigen in Melanoma (PRAME) has been widely investigated in the skin, mainly in melanocytic tumors, and constitutes an aid in differentiating benign from malignant lesions. Very few others studies have been performed on non-melanocytic tumors. Materials We investigated the immunohistochemical expression of PRAME on a series of 11 neurothekeomas, together with three cases of nerve sheath myxoma and one case of plexiform fibrohistiocytic tumor, in order to evaluate the presence and usefulness of this marker in their differential diagnosis. Results PRAME was variably expressed in all cases of NTK, with moderate intensity in three cases, and faint in the remaining cases; on the contrary, cases of NSM and PFT were negative. Conclusions This study expands the entities of cutaneous non-melanocytic tumors expressing PRAME, and confirms that this marker is not restricted to malignant tumors. Expression of PRAME in NTK does not seem to be related to distinctive histopathologic features. This article is protected by copyright. All rights reserved.

Transgender women (TW) worldwide have a high prevalence of HIV, and TW with HIV encounter numerous healthcare barriers. It is critical to develop evidence-informed interventions to improve their engagement in healthcare to achieve durable viral suppression (VS). We evaluated whether participation in one of nine interventions designed specifically for TW was associated with improved engagement in HIV care among transgender women of colour (TWC).Between 2013 and 2017, nine US organizations implemented nine distinct and innovative HIV care engagement interventions with diverse strategies, including: individual and group sessions, case management and navigation, outreach, drop-in spaces, peer support and/or incentives to engage TWC with HIV in care. The organizations enrolled 858 TWC, conducted surveys, captured intervention exposure data and extracted medical record data. Our evaluation of the interventions employed a pre-post design and examined four outcomes-any HIV care visit, antiretroviral therapy (ART) prescription, retention in HIV care and VS (both overall and among those with a clinic visit and viral load test), at baseline and every 6 months for 24 months. We employed logistic generalized estimating equations to assess the relative odds of each outcome at 12 and 24 months compared to baseline.Overall, 79% of participants were exposed to at least one intervention activity. Over 24 months of follow-up, participants received services for a median of over 6 hours (range: 3-69 hours/participant). Compared to baseline, significantly (plt;0.05) greater odds were demonstrated at both 12 and 24 months for three outcomes: prescription of ART (ORs: 1.42 at 12 months, 1.49 at 24 months), VS among all participants (ORs: 1.49, 1.54) and VS among those with a clinic visit and viral load test (ORs: 1.53, 1.98). The outcomes of any HIV care visit and retention in HIV care had significantly greater odds (ORs: 1.38 and 1.58, respectively) only at 12 months compared to baseline.These evaluation results illustrate promising approaches to improve engagement in HIV care and VS among TWC with HIV. Continued development, adaptation and scale-up of culturally tailored HIV care interventions for this key population are necessary to meet the UNAIDS 95-95-95 goals.

Traditional movement economy (ME) measures the energetic cost of in-line running. However, it is debatable whether such a measure is representative of movement efficiency for team sport athletes who are required to run and change direction repeatedly. This study evaluated ME during both in-line running and runs with directional changes and provided a preliminary exploration as to whether these abilities discriminate soccer players according to playing position, level, and sex. Forty-three soccer players were assessed for ME as extrapolated from oxygen uptake during in-line running (RE) and running with changes of directions (using 20 and 10 m shuttle runs [SRE20 and SRE10]) at 8.4 km/h mean speed. ME worsened with change of direction frequency (p

Background: Exaggerated exercise blood pressure (EEBP) during clinical exercise testing is associated with poor blood pressure (BP) control and cardiovascular disease (CVD). Type-2 diabetes (T2DM) is thought to be associated with increased prevalence of EEBP, but this has never been definitively determined and was the aim of this study. Methods: Clinical exercise test records were analyzed from 13 268 people (aged 53±13 years, 59% male) who completed the Bruce treadmill protocol (stages 1–4, and peak) at 4 Australian public hospitals. Records (including BP) were linked to administrative health datasets (hospital and emergency admissions) to define clinical characteristics and classify T2DM (n=1199) versus no T2DM (n=12 069). EEBP was defined as systolic BP ≥90th percentile at each test stage. Exercise BP was regressed on T2DM history and adjusted for CVD and risk factors. Results: Prevalence of EEBP (age, sex, preexercise BP, hypertension history, CVD history and aerobic capacity adjusted) was 12% to 51% greater in T2DM versus no T2DM (prevalence ratio [95% CI], stage 1, 1.12 [1.02–1.24]; stage 2, 1.51 [1.41–1.61]; stage 3, 1.25 [1.10–1.42]; peak, 1.18 [1.09–1.29]). At stages 1 to 3, 8.6% to 15.8% (4.8%–9.7% T2DM versus 3.5% to 6.1% no-T2DM) of people with ‘normal’ preexercise BP ( Conclusions: People with T2DM have higher prevalence of EEBP and exercise systolic BP independent of CVD and many of its known risk factors. Clinicians supervising exercise testing should be alerted to increased likelihood of EEBP and thus poor BP control warranting follow-up care in people with T2DM.

Traditional movement economy (ME) measures the energetic cost of in-line running. However, it is debatable whether such a measure is representative of movement efficiency for team sport athletes who are required to run and change direction repeatedly. This study evaluated ME during both in-line running and runs with directional changes and provided a preliminary exploration as to whether these abilities discriminate soccer players according to playing position, level, and sex. Forty-three soccer players were assessed for ME as extrapolated from oxygen uptake during in-line running (RE) and running with changes of directions (using 20 and 10 m shuttle runs [SRE20 and SRE10]) at 8.4 km/h mean speed. ME worsened with change of direction frequency (p

INTRODUCTION: Patients with inborn errors of metabolism causing fasting intolerance can experience acute metabolic decompensations. Long-term data on outcomes using emergency letters are lacking.METHODS: This is a retrospective, observational, single-center study of the use of emergency letters based on a generic emergency protocol in patients with hepatic glycogen storage diseases (GSD) or fatty acid oxidation disorders (FAOD). Data on hospital admissions, initial laboratory results and serious adverse events were collected. Subsequently, the website www.emergencyprotocol.net was generated in the context of the CONNECT MetabERN eHealth project following multiple meetings, protocol revisions and translations.RESULTS: Representing 470 emergency protocol years, 127 hospital admissions were documented in 54/128(42%) patients who made use of emergency letters generated based on the generic emergency protocol. Hypoglycemia (here defined as glucose concentration 5 years. Convulsions, coma or death were not documented. By providing basic information, emergency letters for individual patients with hepatic GSD or the main FAOD can be generated at www.emergencyprotocol.net, in 9 different languages.DISCUSSION: Generic emergency protocols are safe and easy for home management by the caregivers and the first hour in-hospital management to prevent metabolic emergencies in patients with hepatic GSD and medium-chain Acyl CoA dehydrogenase deficiency. The website www.emergencyprotocol.net is designed to support families and healthcare providers to generate personalized emergency letters for patients with hepatic GSD and the main FAOD. This article is protected by copyright. All rights reserved.

Summary We present the case of a 69-year-old woman who attended the Endocrinology Unit of Modena for a suspicious lymph node in the left cervical compartment discovered during the follow-up of a recurrent gynecological malignancy. At neck ultrasonography, a thyroid goiter was detected, and the further cytological examination was inconclusive for thyroid nodule and compatible with a localization of an adenocarcinoma with papillary architecture for the lymph node. The histological examination after a left neck dissection confirmed the presence of an intracapsular metastasis of a papillary carcinoma immunohistochemically focally positive for thyroid transcription factor 1 and paired box 8 and negative for thyroglobulin. Subsequently, in the suspicion of a thyroid primitiveness, a total thyroidectomy was performed, revealing an intraparenchymal follicular variant of papillary thyroid carcinoma of 2 mm in the right lobe. During the follow-up, the appearance of a suspected cervical metastatic lesion led to another neck dissection, histologically compatible with a papillary carcinoma localization, immunohistochemically focally positive for thyroid transcription factor 1 and paired box 8, and negative for thyroglobulin. The histological revision of surgical specimens suggests the cervical recurrence of the prior gynecological cancer, rather than a thyroid carcinoma metastasis. The case described shows how carefully the cytological, histological and immunoistochemical results must be evaluated in oncological management, considering the whole patient’s history. Learning points Neck lymph node metastases occasionally originate from anatomically distant primary sites, such as breast, lung, gastro-intestinal tract, genito-urinary tract and CNS. Histological and immunohistochemical evaluations play an important role to identify the primary malignant site, although in some cases they could mislead the clinicians. A multidisciplinary approach and the evaluation of the whole medical history of the patient are mandatory to guide the diagnostic-therapeutic path and to avoid unnecessary treatments.

Methylcitric acid (MCA) analysis has been mainly utilized for the diagnosis of propionate disorders or as a second-tier test in newborn screening, but its utility for patients monitoring still needs to be established. We explored the potential contribution of MCA in the long-term management of organic acidurias. We prospectively evaluated plasma MCA and its relationship with disease biomarkers, clinical status, and disease burden in 22 patients, 13 with propionic acidemia (PA) and nine with methylmalonic acidemia (MMA) on standard treatment and/or after transplantation. Samples were collected at scheduled routine controls or during episodes of metabolic decompensation (MD), 10 patients were evaluated after transplantation (six liver, two combined liver and kidney, 2 kidney). MCA levels were higher in PA compared to MMA and its levels were not influenced by the clinical status (MD vs well state). In MMA, MCA was higher in elder patients and, along with fibroblast growth factor 21 (FGF21) and plasma methylmalonic acid, negatively correlated with GFR. In both diseases, MCA correlated with ammonia, glycine, lysine, C3, and the C3/C2, C3/C16 ratios. The disease burden showed a direct correlation with MCA and FGF21, for both diseases. All transplanted patients showed a significant reduction of MCA in comparison to baseline values, with some differences dependent on the type of transplantation. Our study provided new insights in understanding the disease pathophysiology, showing similarities between MCA and FGF21 in predicting disease burden, long-term complications and in evaluating the impact of organ transplantation.

Objective:Despite support for the role of exercise in improving physical and mental health for various psychiatric disorders, few service implementation evaluations within diverse hospital environments exist. This study presents the feasibility and implementation of a clinical exercise physiology service within a hospital mental health service.Method:Feasibility and service data were collected from databases and self-report (consumer and staff) for 6 months from the commencement of new exercise services (gym and group sessions) for community and inpatients (one secure and three open wards).Results:One hundred and twenty consumers engaged with exercise services with 70 direct referrals over the 6-month audit period (mean age 40 ± 13 years (19–69); 41% male). The overwhelming reason for referral was related to weight loss/management (65.7%), with the majority of patients (51%) presenting with schizophrenia spectrum and other psychotic disorders. Further, 549 exercise service interactions were delivered and 78% gym attendees and 69% group session attendees rated the exercise sessions as ‘Good’ or ‘Great’, and intention to return ranged from 78% for inpatient gym sessions to 91% for community gym sessions.Conclusions:Embedding exercise physiology into a mental health service is feasible and well accepted and the evaluation of long-term consumer outcomes in ‘real-world’ will serve as a crucial step.

The population of adults living with congenital heart disease (CHD) has grown rapidly in recent decades due to major advances in surgical and medical care. Although the benefits of physical activity (PA) and exercise are well recognised in the management of chronic diseases, the therapeutic role of exercise for the CHD population has been under-studied and under-recognised. In fact, people living with complex CHD have traditionally been advised against participation in moderate or vigorous PA due to safety concerns. However, a small but growing body of literature has demonstrated that PA and exercise are safe and beneficial for the vast majority of people with CHD following appropriate screening. Exercise training (ET) is a potent therapy to improve well-being and cardiorespiratory fitness, which likely has important implications for prognosis. This has led to ET becoming an increasingly important adjunct to medical therapy in the management of this group who frequently have significant exercise limitation and complex medical issues. However, there is currently limited evidence-based guidance that has been published regarding appropriate exercise prescription in adults with CHD. This article aims to provide an overview of different congenital heart conditions, their impact on the exercise response, and to provide considerations and recommendations for ET in adolescents and adults living with CHD based on the available literature.

Exercise training is an important component of multidisciplinary heart failure management. However, the effects of aerobic training (AT) versus resistance training (RT) on cardiac function in patients with heart failure with reduced ejection fraction are not well defined. The aim of this study was to evaluate the impact of these exercise modalities on echocardiographic parameters.Participants with stable heart failure with reduced ejection fraction (ejection fraction 50%) were randomized to 12 weeks of AT, RT, or untrained control. Exercise was performed at matched relative intensities of each training modality (50%-70% of maximum). Echocardiography and cardiopulmonary exercise testing were performed at baseline and after 12 weeks of training.Thirty-eight participants were randomized, and 12 in each group completed the intervention (mean age, 61.5 ± 1.7 years; 89% men). Peak oxygen consumption increased from 14.5 ± 1.3 to 17.2 ± 1.6 ml · minThere is a differential effect of AT versus RT on some echocardiographic parameters in patients with heart failure with reduced ejection fraction. AT was associated with evidence of worsening myocardial diastolic function, whereas this was not apparent after RT. Further studies are indicated to investigate the long-term clinical significance of these adaptations.

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Cerebral blood flow during exercise is impaired in patients with heart failure implanted with left ventricular assist devices (LVADs). Our aim was to determine whether a 3-mo exercise training program could mitigate cerebrovascular dysfunction. Internal carotid artery (ICA) blood flow and intracranial middle (MCA v) and posterior cerebral (PCA v) artery velocities were measured continuously using Doppler ultrasound, alongside cardiorespiratory measures at rest and in response to an incremental cycle ergometer exercise protocol in 12 LVAD participants (5 female, 53.6 ± 11.8 yr; 84.2 ± 15.7 kg; 1.73 ± 0.08) pre- (PreTR) and post- (PostTR) completion of a 3-mo supervised exercise rehabilitation program. At rest, only PCAv was different PostTR (38.1 ± 10.4 cm/s) compared with PreTR (43.0 ± 10.8 cm/s; P < 0.05). PreTR, the reduction in PCAv observed from rest to exercise (5.2 ± 1.8%) was mitigated PostTR ( P < 0.001). Similarly, exercise training enhanced ICA flow during submaximal exercise (~8.6 ± 13.7%), resulting in increased ICA flow PostTR compared with a reduced flow PreTR ( P < 0.001). Although both end-tidal partial pressure of carbon dioxide and mean arterial pressure responses during incremental exercise were greater PostTR than PreTR, only the improved [Formula: see text] was related to the improved ICA flow ( R2 = 0.14; P < 0.05). Our findings suggest that short-term exercise training improves cerebrovascular function during exercise in patients with LVADs. This finding should encourage future studies investigating long-term exercise training and cerebral and peripheral vascular adaptation. NEW & NOTEWORTHY Left ventricular assist devices, now used as destination therapy in end-stage heart failure, enable patients to undertake rehabilitative exercise training. We show, for the first time in humans, that training improves cerebrovascular function during exercise in patients with left ventricular assist devices. This finding may have implications for cerebrovascular health in patients with heart failure.

IntroductionFunctional hypothalamic amenorrhea (FHA) is a clinical condition associated with high levels of physiological and psychological stress ranging from weight loss to maladaptive behavior and coping skills. A reliable measure of the psychophysiological response to stress and the ability to cope with stimuli is heart rate variability (HRV). Through the sympathetic (SNS) and parasympathetic nervous system (PNS), the autonomic nervous system (ANS) promotes various changes in HRV that reflect the individual’s psychophysiological response to stress. FHA patients are characterized by high levels of PNS activation during psychological load, suggesting that parasympathetic hyperactivation could be a pathology marker.MethodsIn the present study, we examine changes in HRV during observation of erotic, neutral, and disgusting images in 10 patients with FHA [(mean ± S.D.) age: 26.8 ± 5.9] and in 9 controls (age: 25.4 ± 6.4; BMI: 22.47 ± 2.97) to assess the differential activation of PNS and SNS between FHA patients and controls matched for age and without other clinical conditions.ResultsOur results showed that FHA patients had significantly higher HRV activation while observing high emotional value images and not during the observation of neutral images confirming a parasympathetic hyperactivation.DiscussionHRV and cognitive and psychological testing, could provide new insights into understanding such a clinically understudied condition and provide further tools for clinical diagnosis and treatment.

Made available in DSpace on 2022-05-01T10:03:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Purpose: Laser light has biological effects that can modulate inflammatory processes. Thus, this study aimed to evaluate the effects of photobiomodulation (PBM) therapy on pain, edema, and trismus after the extraction of retained third molars. Methods: A split-mouth, double-blind, randomized clinical trial (RCT) was conducted in 13 patients with similar bilateral third molars who received intraoral application PBM therapy at 4 points with a diode laser at 810 nm wavelength, 6 J (100 mW, 60 seconds/point) on 1 side (the PBM side); and laser irradiation simulation on the other side (SHAM side). The pain was assessed through visual analog scale (VAS) at 0, 12, 24, 48, and 72 hours, number of analgesic-relief (NAR), and mean time of first analgesic use; edema, through VAS, and linear facial measurements at 0, 24, 48, and 72 hours; and trismus, through the mouth opening measurements at 0, 24, 48, and 72 hours. The repeated-measures analysis was applied to assess the effect of the treatment, followed by Tukey's post hoc test for multiple comparisons (P Research Fellow Skeletal Biology Research Center Department of Oral and Maxillofacial Surgery Massachusetts General Hospital (MGH) Harvard School of Dental Medicine Professor of Department of Biomedical Surgical and Dental Sciences Implant Center for Edentulism and Jawbone Atrophies Maxillofacial Surgery and Odontostomatology Unit Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico University of Milan Professor of Oral & Maxillo Facial Surgery Faculty of Dentistry Department of Clinic and Surgery Federal University of Alfenas (UNIFAL) Professor of Periodontology School of Dentistry Department of Diagnose and Surgery São Paulo State University (UNESP) Professor of Oral & Maxillo Facial Surgery School of Dentistry Department of Diagnose and Surgery São Paulo State University (UNESP) PhD Student Department of Diagnose and Surgery São Paulo State University (UNESP) School of Dentistry Professor of Periodontology School of Dentistry Department of Diagnose and Surgery São Paulo State University (UNESP) Professor of Oral & Maxillo Facial Surgery School of Dentistry Department of Diagnose and Surgery São Paulo State University (UNESP)

Splenic marginal zone B-cell lymphoma (SMZL) is a heterogeneous clinico-biological entity. The clinical course is variable, multiple genes are mutated with no unifying mechanism, and essential regulatory pathways and surrounding microenvironments are diverse. We sought to clarify the heterogeneity of SMZL by resolving different subgroups and their underlying genomic abnormalities, pathway signatures, and microenvironment compositions to uncover biomarkers and therapeutic vulnerabilities. We studied 303 SMZL spleen samples collected through the IELSG46 multicenter international study (NCT02945319) by using a multiplatform approach. We carried out genetic and phenotypic analyses, defined self-organized signatures, validated the findings in independent primary tumor metadata and determined correlations with outcome data. We identified 2 prominent genetic clusters in SMZL, termed NNK (58% of cases, harboring NF-κB, NOTCH, and KLF2 modules) and DMT (32% of cases, with DNA-damage response, MAPK, and TLR modules). Genetic aberrations in multiple genes as well as cytogenetic and immunogenetic features distinguished NNK- from DMT-SMZLs. These genetic clusters not only have distinct underpinning biology, as judged by differences in gene-expression signatures, but also different outcomes, with inferior survival in NNK-SMZLs. Digital cytometry and in situ profiling segregated 2 basic types of SMZL immune microenvironments termed immune-suppressive SMZL (50% of cases, associated with inflammatory cells and immune checkpoint activation) and immune-silent SMZL (50% of cases, associated with an immune-excluded phenotype) with distinct mutational and clinical connotations. In summary, we propose a nosology of SMZL that can implement its classification and also aid in the development of rationally targeted treatments.

A large number of inborn errors of metabolism present with hypoglycemia. Impairment of glucose homeostasis may arise from different biochemical pathways involving insulin secretion, fatty acid oxidation, ketone bodies formation and degradation, glycogen metabolism, fructose and galactose metabolism, branched chain aminoacids and tyrosine metabolism, mitochondrial function and glycosylation proteins mechanisms. Historically, genetic analysis consisted of highly detailed molecular testing of nominated single genes. However, more recently, the genetic heterogeneity of these conditions imposed to perform extensive molecular testing within a useful timeframe via new generation sequencing technology. Indeed, the establishment of a rapid diagnosis drives specific nutritional and medical therapies. The biochemical and clinical phenotypes are critical to guide the molecular analysis toward those clusters of genes involved in specific pathways, and address data interpretation regarding the finding of possible disease-causing variants at first reported as variants of uncertain significance in known genes or the discovery of new disease genes. Also, the trio’s analysis allows genetic counseling for recurrence risk in further pregnancies. Besides, this approach is allowing to expand the phenotypic characterization of a disease when pathogenic variants give raise to unexpected clinical pictures. Multidisciplinary input and collaboration are increasingly key for addressing the analysis and interpreting the significance of the genetic results, allowing rapidly their translation from bench to bedside.

Frailty is highly prevalent in heart failure (HF) patients. HF is associated with oxidative stress and chronic inflammation, which impair oxygen use by skeletal muscles. Little is known about the influence of frailty on vascular responsiveness and tissue oxygenation.Analyze the influence of frailty on vascular responsiveness and muscle oxygenation in elderly individuals with and without HF.Individuals aged ≥60 years, with or without HF, were evaluated for frailty (phenotype). Near-infrared spectroscopy (NIRS) was used to assess muscle oxygenation at rest (oxygen saturation - StOResults were grouped according to the frailty phenotype: non-frail, pre-frail, and frail. Shapiro-Wilk test was used to assess normality. Data were compared using a two-way analysis of variance (ANOVA). Bonferroni post hoc test was applied to determine the influence of frailty or HF on NIRS variables. SPSS software was used in the analyses; p 0.05 was considered significant.55 elderly participants (61.8% female; 70.4 ± 7.2 years old; 28 HF patients) participated in the study. 32.7% (n = 18) were classified as non-frail, 43.3% (n = 24) as pre-frail, and 23.6% (n = 13) as frail. The analysis of vascular responsiveness (n = 52) identified an influence (p 0.05) of frailty on the reperfusion rate (slope 2 and ∆StOThe coexistence of frailty and HF seems to impair vascular responsiveness, as frail elderly participants with HF presented lower reperfusion rates and higher desaturation levels during the arterial occlusion test. However, the presence of frailty or HF alone had no influence on muscle oxygenation at rest or during exercise.

Nivolumab is an anti&ndash, PD-1 antibody that restores the antitumour immune function of T cells, blocking the binding of PD-1 with its ligand PD-L1. PD-1 is expressed on T cells and interacts with PD-L1 on tumour cells. The PD-1&ndash, PD-L1 link inhibits T cell activation. In metastatic melanoma, PD-1&ndash, PD-L1 binding plays a critical role, and the advent of the immune checkpoint inhibitor nivolumab has delivered new and effective treatment options with proven clinical benefit. In the present study, we evaluated the efficacy of nivolumab in elderly patients with metastatic melanoma. The study enrolled 55 elderly patients (75 years of age and older) with a diagnosis of metastatic melanoma. Primary endpoints of the study were progression-free survival (pfs) and the objective response rate, secondary endpoints were overall survival, reduction in serum lactate dehydrogenase (ldh) from before to after treatment, and tolerability. Nivolumab was well tolerated and resulted in good disease control, with a manageable toxicity profile and significant clinical benefit. The duration of pfs was 5.1 months (95% confidence interval: 3.5 months to 6.8 months). A significant correlation was observed between reduction in serum ldh and pfs: 0.60 (95% confidence interval: 0.28 to 0.86, p = 0.002). Nivolumab is an immunotherapy treatment that has proved to be an effective and well-tolerated therapeutic option in elderly patients with metastatic melanoma.

The incidence of endometriosis in middle-aged women is not minimal compared to that in the reproductive age group. The treatment of affected women after childbearing age to the natural transition toward menopause has received considerably poor attention. Disease management is problematic for these women due to increased contraindications regarding hormonal treatment and the possibility for malignant transformation, considering the increased cancer risk in patients with a long-standing history of the disease. This state-of-the-art review aims for the first time to assess the benefits of the available therapies to help guide treatment decisions for the care of endometriosis in women approaching menopause. Progestins are proven effective in reducing pain and should be preferred in these women. According to the international guidelines that lack precise recommendations, hysterectomy with bilateral salpingo-oophorectomy should be the definitive therapy in women who have completed their reproductive arc, if medical therapy has failed. Strict surveillance or surgery with removal of affected gonads should be considered in cases of long-standing or recurrent endometriomas, especially in the presence of modifications of ultrasonographic cyst patterns. Although rare, malignant transformation of various tissues in endometriosis patients has been described, and management is herein discussed.

The handle-to-hand correspondence effect consists of faster and more accurate responses when the responding hand is aligned with the handle side of an object tool, compared to when they lay on opposite sides. This effect has been attributed to the activation of affordances. Recent studies, however, claimed that it may depend on the spatial coding of the object on the basis of its visual asymmetry (location-coding account). Affordances are namely direct and meaningful relations between recognized objects and the observers’ action system. Therefore, any manipulation that disrupts the body structure of object tools could potentially affect their identification and prevent the activation of affordances. The present study investigated the nature of the handle-to-hand correspondence effects by manipulating structural asymmetry and visual salience of object tools, while preserving their integrity that is, leaving unaltered the original possibilities to activate grasping affordances. Three experiments were run. Results were consistent with the location-coding account and claim for accurate control of visual asymmetries in object stimuli during investigation of affordance effects.

The genetic causes of global developmental delay (GDD) and intellectual disability (ID) are diverse and include variants in numerous ion channels and transporters. Loss-of-function variants in all five endosomal/lysosomal members of the CLC family of Cl− channels and Cl−/H+ exchangers lead to pathology in mice, humans, or both. We have identified nine variants in CLCN3, the gene encoding CIC-3, in 11 individuals with GDD/ID and neurodevelopmental disorders of varying severity. In addition to a homozygous frameshift variant in two siblings, we identified eight different heterozygous de novo missense variants. All have GDD/ID, mood or behavioral disorders, and dysmorphic features; 9/11 have structural brain abnormalities; and 6/11 have seizures. The homozygous variants are predicted to cause loss of ClC-3 function, resulting in severe neurological disease similar to the phenotype observed in Clcn3−/− mice. Their MRIs show possible neurodegeneration with thin corpora callosa and decreased white matter volumes. Individuals with heterozygous variants had a range of neurodevelopmental anomalies including agenesis of the corpus callosum, pons hypoplasia, and increased gyral folding. To characterize the altered function of the exchanger, electrophysiological analyses were performed in Xenopus oocytes and mammalian cells. Two variants, p.Ile607Thr and p.Thr570Ile, had increased currents at negative cytoplasmic voltages and loss of inhibition by luminal acidic pH. In contrast, two other variants showed no significant difference in the current properties. Overall, our work establishes a role for CLCN3 in human neurodevelopment and shows that both homozygous loss of ClC-3 and heterozygous variants can lead to GDD/ID and neuroanatomical abnormalities.

AIMS Spitzoid tumours have been shown to harbour exclusive kinase fusions. Few studies have analysed substantial numbers of ROS1-rearranged lesions. The aim of the present study was to investigate also their immunohistochemical profile. METHODS AND RESULTS Among a group of 35 spitzoid tumours, of which 34 were consecutively diagnosed in a 3-year period, we found 11 ROS1 cases that were immunohistochemically positive, from 10 patients, eight of whom were female and two of whom were male, and who were aged 3-52 years (median, 29 years); most lesions (eight) were localized on the lower extremities. Four patterns of immunostaining were observed: cytoplasmic granular diffuse (six cases), sparse cytoplasmic granules (three cases), paranuclear dots (one case), and nuclear (one case). Fluorescence in-situ hybridisation (FISH) analysis showed all cases to be rearranged (cut-off of >15%). RNA next-generation sequencing (NGS) analysis showed specific fusions of ROS1 in four cases: two with PWWP2A, one with PPFIBP1, and one with ZCCHC8. DNA NGS analysis showed in five cases, specific mutations of AKT, EGFR, NRAS, MYC, ALK, and KIT. ROS1 lesions belonged predominantly to the 'atypical Spitz tumour' group, and showed mainly a nested histological pattern. Interestingly, one patient developed two ROS1-positive lesions. CONCLUSIONS Immunohistochemistry showed 100% sensitivity and specificity as compared with the FISH results, corresponding to ROS1 rearrangement in 31% of cases studied. These observations shed new light on the value of immunohistochemical evaluation of ROS1 in spitzoid tumours. ROS1 patterns of immunostaining probably reflect different subcellular localisations of ROS1 fusions, although no specific correlations were found in the cases studied. Immunohistochemistry and FISH were the most sensitive techniques for detecting ROS1 rearrangement in this subset of neoplasms.

Purpose To evaluate the long-term outcome of dental implants placed with a staged procedure in resorbed alveolar ridges reconstructed with iliac crest autogenous onlay grafts. Materials and methods All consecutive patients treated with iliac crest onlay bone grafts and dental implants were retrospectively evaluated. During the appointment, clinical and radiological examinations were conducted to assess implant survival. A survived implant was defined as an implant still stable and in function at the follow-up visit. Implant survival was estimated at the implant level using Kaplan-Meier analyses. The cumulative survival rate was estimated using a life-table analysis. Subgroup analyses were performed for age, position, and type of retention using the log-rank test. A p-value of Results The cohort consisted of 21 female subjects receiving a total of 140 rough-surface titanium implants. Of them, 128 survived and 12 failed, yielding a cumulative survival rate of 91.1% over a median survival time of 312 months. Implants supporting cement-retained prostheses exhibithed lower survival rate compared to screw-retained restorations (p = 0.001). Conclusion Implants placed in bone augmented with iliac crest onlay grafts showed high long-term survival rates. Cement-retained restorations were more prone to develop implant failures.

INTRODUCTION In healthy individuals, cerebral blood flow (CBF) increases during exercise, but few studies have compared changes in CBF during exercise in patients with heart failure (HF) to healthy controls (CTRL) or assessed the effects of left ventricular assist devices (LVAD). We hypothesized that subjects implanted with LVAD would exhibit impaired cerebrovascular responses to cycle exercise when compared with age- and sex-matched healthy CTRL subjects but would have enhanced responses relative to subjects with HF. METHODS Internal carotid artery (ICA) blood flow and intracranial middle (MCAv) and posterior cerebral (PCAv) artery velocities were measured continuously using Doppler ultrasound, alongside cardiorespiratory measures at rest and in response to an incremental submaximal cycle ergometer exercise protocol in nine LVAD participants (58 ± 15 yr, 87 ± 16 kg, 172 ± 8 cm, six females), nine age- and sex-matched subjects with HF (58 ± 8 yr, 84 ± 11 kg, 177 ± 6 cm), and nine CTRL (55 ± 14 yr, 74 ± 16 kg, 168 ± 10 cm). RESULTS At rest, ICA hemodynamics (velocity, shear rate, and flow) were greater in CTRL and LVAD than that in HF (P < 0.05). Higher MCAv (+5.52 ± 1.59 cm·s, P = 0.003) and PCAv (+5.82 ± 1.41 cm·s, P = 0.001) were also observed in LVAD subjects than healthy CTRL. During exercise, ICA flow increased at all workloads in CTRL, but not in HF or LVAD groups. MCAv increased from baseline in both HF and CTRL participants (P = 0.0001), but not in LVAD subjects. Nonetheless, CTRL and LVAD showed higher MCAv (P = 0.006) and PCAv (P < 0.0001) values throughout exercise than HF. CONCLUSION Our findings indicate that LVAD subjects exhibit higher CBF at rest and during exercise than matched HF participants but attenuated brain blood flows during exercise when compared with healthy subjects. CBF should be considered when designing exercise training interventions in patients with HF and LVAD.

Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age 35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end point. A DFS hazard ratio (HR)

Endothelial function, assessed using brachial artery flow-mediated dilation (FMD), predicts future cardiovascular disease (CVD) risk. This study established age- and sex-specific reference intervals for brachial artery FMD in healthy individuals and examined the relation with CVD risk factors. In a retrospective study design, we pooled brachial artery FMD (acquired according to expert-consensus guidelines for FMD protocol and analysis) and participant characteristics/medical history from 5362 individuals (4–84 years; 2076 females). Healthy individuals (n=1403 [582 females]) were used to generate age-/sex-specific percentile curves. Subsequently, we included individuals with CVD risk factors, without overt disease (unmedicated n=3167 [1247 females] and medicated n=792 [247 females]). Multiple linear regression tested the relation of CVD risk factors (body mass index, blood pressure, cholesterol, diabetes, dyslipidemia, and smoking) with FMD. Healthy males showed a negative, curvilinear relation between FMD and age, while females revealed a negative linear relation that started higher but declined at a faster rate than males. Age- and sex-specific differences in FMD relate, at least partly, to baseline artery diameter. FMD was related to CVD risk factors in unmedicated (eg, systolic/diastolic blood pressure) and medicated individuals (eg, diabetes/dyslipidemia). Sex mediated some of these effects ( P

High suspicion of scar endometriosis are painful no-dule in the abdominal scar. Wide surgical excision is the treatment of choice.Endometriosis has been described as the presence of endometrial tissue outside uterine cavity. Scar endometriosis (SE) is a rare disease reported in 0.03-1.08% of women following gynaecologic surgery. In our retrospective observational cohort study we studied anamnesis, symptoms, surgical procedures and outcomes linked to scar endometriosis in our medical experience from 2004 to 2018.We reviewed the medical records of 46 patients with a histopathological diagnosis of SE. All patients had a history of at least one previous caesarean section (n=46, 100%). Forty-two patients (91,3%) complained gradually growing nodular abdominal mass near or adjacent to caesarean incision scar, while only 4 patients (8,6%) complained aspecific abdominal pain. Ultrasound scan was performed in all patients (n=46, 100%) and mean size of the nodules at US was 26,8 ± 13,8 mm.All patients underwent surgery. Seven patients (15,2%) needed mesh implantation, while 39 patients (84,8%) underwent local resection with reconstruction of muscle fascia. Mean follow-up was 31,6 ± 14 months and no patients reported local recurrence of disease.

Background: Melanoma is the leading cause of death due to cutaneous malignancy and its incidence is on the rise. Several signaling pathways, including receptor tyrosine kinases, have a role in the development and progression of melanocytic lesions and malignant melanoma. Among those, the hepatocyte growth factor (HGF)/c-met axis is emerging as a critical player because it can play a role in drug resistance. Indeed, 50% of melanoma patients present BRAF mutations, however, all responders develop resistance to the inhibitors typically within one year of treatment. Interestingly, BRAF inhibitors induce reactive oxygen species (ROS) in melanoma cells, therefore, the aim of this study was to investigate a possible interplay between HGF/c-met and ROS sources, such as NADPH oxidases (Nox). Methods: The expression of c-met and Nox were quantified in 60 patients with primary cutaneous melanoma. In vitro experiments on melanoma primary cells and the cell line were performed to dissect the underpinned molecular mechanism. Results: The outcome of interest was the correlation between the high positivity for both Nox4 and c-met and metastasis occurring at least 1 year later than melanoma diagnosis in BRAF mutated patients, in contrast to nonmutated. In vitro experiments demonstrated that the axis HGF/c-met/Nox4/ROS triggers the epithelial-mesenchymal transition. Conclusions: The observed correlation suggests an interplay between c-met and Nox4 in promoting the onset of metastasis. This study suggests that Nox4 inhibitors could be associated to the current therapy used to treat melanoma patients with BRAF mutations.

This study aimed to evaluate the effect of high-intensity interval training shock microcycles (HIITSM) on endurance, running economy and change of direction economy in female soccer players. Nineteen sub-elite female soccer players were randomised to two groups: HIITSM (10 HIIT sessions over 13 days) or HIITTRAD (4 HIIT sessions over 13 days) interventions. Endurance performance was evaluated through the 30–15 intermittent fitness test (30–15IFT); running economy over a 5-min treadmill run; and change of direction economy over two conditions: (1) 5-min 20m shuttle run, and (2) 5-min 10m shuttle run. HIITSM significantly improved 30–15IFT scores compared to baseline (+4.4%, p=0.009; d=0.96) and 30–15IFT scores relative to HIITTRAD (p=0.002; d=2.01). There was no significant interaction (group×time) for running economy and change of direction economy. Pre- to post- intervention there was a significant main time effect for blood lactate over 20m and 10m shuttle runs (p

The tumor immune microenvironment (TME) and immune checkpoints have been reported to serve a role in the pathogenesis of malignant mesothelioma (MM) and treatment outcome. Additionally, mismatch Repair (MMR) deficiency appears to enhance the response to checkpoints blockade in several tumors. The aim of the present study was to analyze programmed death‑1 ligand 1 (PD‑L1) expression in MM and to characterize the TME. This could help to understand the immune response, and evaluate its prognostic and predictive values. We also investigated MMR protein expression. We retrospectively analyzed 55 mesotheliomas to determine PD‑L1, CD4+, CD8+, mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6) and PMS1 homolog 2, mismatch repair system component (PMS2) expression. We used an immunoscore (1+, 2+ and 3+) to evaluate tumor‑infiltrating lymphocytes (TILs). TILs were observed in all but two samples (53/55); the majority had an immunoscore 1+ (30/53), while 2+/3+ was reported for 23/53 samples. A predominance of CD8+ was highlighted in 8 cases (15%). PD‑L1 expression of ≥1% on tumor cells was displayed in 40 cases; in 9 of these, ≥50% expression was reported. Of note, alterations in MMR staining was not observed. In addition, survival analysis revealed that epithelioid subtype was associated with better prognosis. We observed a trend towards poorer prognosis for ≥50% PD‑L1 expression on tumor cells, lower immunoscore (1+) and CD8+ TIL predominance. The present study highlighted the importance of exploring the TME and the standardization of PD‑L1 assessment guidelines to apply in the field of immunotherapy.

Children born preterm have impaired lung function and altered lung structure. However, there are conflicting reports on how preterm birth impacts aerobic exercise capacity in childhood. We aimed to investigate how neonatal history and a diagnosis of bronchopulmonary dysplasia (BPD) impact the relationship between function and structure of the lung, and aerobic capacity in school-aged children born very preterm.Preterm children (≤ 32 w completed gestation) aged 9-12 years with (n = 38) and without (n = 35) BPD, and term-born controls (n = 31), underwent spirometry, lung volume measurements, gas transfer capacity, a high-resolution computer tomography (CT) scan of the chest, and an incremental treadmill exercise test.Children born preterm with BPD had an elevated breathing frequency to tidal volume ratio compared to term controls (76% vs 63%, p = 0.002). The majority (88%) of preterm children had structural changes on CT scan. There were no differences in peak V̇OChildren born preterm have impaired lung function, and a high prevalence of structural lung abnormalities. However, abnormal lung function and structure do not appear to impact on the aerobic exercise capacity of preterm children at school age.

Objectives Obesity is an increasing health problem that has become a common medical disorder among women of childbearing age, representing worldwide a risk factor for stillbirth. The aim of the study is to evaluate the association between placental histopathologic findings and obesity in stillbirth. Methods Placentas were analyzed according to the Amsterdam consensus statement. Histologic findings in stillbirth from obese and lean mothers were analyzed and compared with those observed in liveborn controls. Results Stillbirth in obese mothers displayed placental pathology in all gestational ages, mostly at term of pregnancy. The most observed placental lesions were those consistent with maternal vascular malperfusion of the placental bed. Decidual arteriopathy and placental infarcts appeared specifically associated with maternal obesity. Moreover, obese women with stillbirth showed the highest cumulative number of placental lesions. Conclusions Considering the significant association between stillbirth, maternal obesity, and placental histopathologic findings, health care providers should be aware about the importance of placental examination in obese women, especially in stillborn cases. The high prevalence of lesions consistent with vascular malperfusion of the placental bed suggests that stillbirth prevention strategies in obese women should rely on the development of tools to study and improve decidual artery functioning early in pregnancy.

BACKGROUND Left ventricular assist device (LVAD) implantation is an established treatment for patients with advanced heart failure. To date, studies evaluating the impact of aerobic training in patients with LVADs have focused on moderate-intensity exercise. METHODS This pilot randomized controlled trial compared the effects of high-intensity interval training (HIIT) with those of moderate-intensity continuous training (MICT) on peak oxygen consumption (VO2 peak) in patients with LVADs. Secondary outcomes included 6-minute walk test distance, flow-mediated dilation, and anthropometry. Assessments were conducted at baseline and after 12 weeks of supervised training performed 3 times weekly. Participants were randomized to HIIT (4 sets of 4 minutes at 80%–90% VO2 reserve, alternating with 3 minutes at 50%–60% VO2 reserve) or MICT groups (28 minutes continuously at 50%–60% VO2 reserve). Within and between-group differences were analyzed using linear mixed models. Data are expressed as marginal means with 95% confidence intervals or as mean ± SD. RESULTS A total of 21 participants were randomized (HIIT: age 57.7 ± 13.1 years; n = 11 and MICT: age 55.6 ± 14.2 years; n = 10) (mean ± SD). No major adverse events occurred in response to training in either group. HIIT significantly improved VO2 peak (15.6 [13.2–17.8] to 18.4 [16.0–20.8] ml/kg/min) (marginal mean [95% CI]) compared with MICT (16.2 [13.8–18.7] to 17.2 [14.6–19.7] ml/kg/min; p CONCLUSION In patients with LVADs, HIIT was well tolerated and increased aerobic capacity more than MICT. These preliminary findings support the prescription of high-intensity exercise in clinically stable patients with LVADs but warrant validation in a larger sample and across a broader range of physiologic and clinical outcomes. CLINICAL TRIAL REGISTRATION URL: https://www.anzctr.org.au , unique identifier: ACTRN12616001596493.

Epithelial ovarian neoplasms can be divided into three distinct clinicopathological groups: benign, malignant and borderline tumours. Borderline tumours are less aggressive than epithelial carcinomas, with an indolent clinical course and delayed recurrence. However, a subset of these cases can progress to malignancy and relapse, and death from recurrent disease can occasionally occur. Telomerase activation is a critical element in cellular immortalisation and cancer. The enzyme telomerase comprises a catalytic subunit (TERT) expressed in various types of cancers and regulated by promoter methylation mainly in epithelial tumours. The aim of this study was to investigate the promoter methylation status and the expression of TERT in 50 serous borderline tumours (SBTs) and their correlation with clinicopathological features and outcome. TERT methylation was analysed by bisulfite pyrosequencing and TERT expression by immunohistochemistry. Methylation of TERT promoter was only observed in four SBTs. A good correlation with immunostochemistry was found: nuclear positivity for TERT expression was observed in the methylated cases, whereas no expression was detected in unmethylated tumours. One of these patients had a recurrence after 7 years and another patient died from the disease. SBTs with hypomethylated tumours and absence of TERT expression showed a good clinical behaviour. Our study highlights the low presence of TERT methylation in SBTs, confirming that these tumours have a different biology than serous carcinomas. Furthermore, the concordance between TERT promoter methylation and TERT expression and their association with clinical outcomes leads to consider TERT alteration as a potential predictive biomarker for recurrence risk identifying patients who should undergo a careful and prolonged follow-up.

Recent reports suggested that direct acting antivirals (DAAs) might favor hepatocellular carcinoma (HCC). In study 1, we studied the proangiogenic liver microenvironment in 242 DAA‐treated chronic hepatitis C patients with advanced fibrosis. Angiopoietin‐2 (ANGPT2) expression was studied in tissue (cirrhotic and/or neoplastic) from recurrent, de novo, nonrecurrent HCC, or patients never developing HCC. Circulating ANGPT2,vascular endothelial growth factor (VEGF), and C‐reactive protein (CRP) were also measured. In study 2, we searched for factors associated with de novo HCC in 257 patients with cirrhosis of different etiologies enrolled in a dedicated prospective study. Thorough biochemical, clinical, hemodynamic, endoscopic, elastographic, and echo‐Doppler work‐up was performed in both studies. In study 1, no patients without cirrhosis developed HCC. Of 183 patients with cirrhosis, 14 of 28 (50.0%) with previous HCC recurred whereas 21 of 155 (13.5%) developed de novo HCC. Patients with recurrent and de novo HCCs had significantly higher liver fibrosis (LF) scores, portal pressure, and systemic inflammation than nonrecurrent HCC or patients never developing HCC. In recurrent/de novo HCC patients, tumor and nontumor ANGPT2 showed an inverse relationship with portal vein velocity (PVv; r = –0.412, P = 0.037 and r = –0.409, P = 0.047 respectively) and a positive relationship with liver stiffness (r = 0.526, P = 0.007; r = 0.525, P = 0.003 respectively). Baseline circulating VEGF and cirrhotic liver ANGPT2 were significantly related (r = 0.414, P = 0.044). VEGF increased during DAAs, remaining stably elevated at 3‐month follow‐up, when it significantly related with serum ANGPT2 (r = 0.531, P = 0.005). ANGPT2 expression in the primary tumor or in cirrhotic tissue before DAAs was independently related with risk of HCC recurrence (odds ratio [OR], 1.137; 95% confidence interval [CI], 1.044‐1.137; P = 0.003) or occurrence (OR, 1.604; 95% CI, 1.080‐2.382; P = 0.019). In study 2, DAA treatment (OR, 4.770; 95% CI, 1.395‐16.316; P = 0.013) and large varices (OR, 3.857; 95% CI, 1.127‐13.203; P = 0.032) were independent predictors of de novo HCC. Conclusion: Our study indicates that DAA‐mediated increase of VEGF favors HCC recurrence/occurrence in susceptible patients, that is, those with more severe fibrosis and splanchnic collateralization, who already have abnormal activation in liver tissues of neo‐angiogenetic pathways, as shown by increased ANGPT2. (Hepatology 2018; 00:000‐000).

Background Telemonitoring enables care providers to remotely support outpatients in self-managing chronic heart failure (CHF), but the objective assessment of patient compliance with self-management recommendations has seldom been studied. Objective This study aimed to evaluate patient compliance with self-management recommendations of an innovative telemonitoring enhanced care program for CHF (ITEC-CHF). Methods We conducted a multicenter randomized controlled trial with a 6-month follow-up. The ITEC-CHF program comprised the provision of Bluetooth-enabled scales linked to a call center and nurse care services to assist participants with weight monitoring compliance. Compliance was defined a priori as weighing at least 4 days per week, analyzed objectively from weight recordings on the scales. The intention-to-treat principle was used to perform the analysis. Results A total of 184 participants (141/184, 76.6% male), with a mean age of 70.1 (SD 12.3) years, were randomized to receive either ITEC-CHF (n=91) or usual care (control; n=93), of which 67 ITEC-CHF and 81 control participants completed the intervention. For the compliance criterion of weighing at least 4 days per week, the proportion of compliant participants in the ITEC-CHF group was not significantly higher than that in the control group (ITEC-CHF: 67/91, 74% vs control: 56/91, 60%; P=.06). However, the proportion of ITEC-CHF participants achieving the stricter compliance standard of at least 6 days a week was significantly higher than that in the control group (ITEC-CHF: 41/91, 45% vs control: 23/93, 25%; P=.005). Conclusions ITEC-CHF improved participant compliance with weight monitoring, although the withdrawal rate was high. Telemonitoring is a promising method for supporting both patients and clinicians in the management of CHF. However, further refinements are required to optimize this model of care. Trial Registration Australian New Zealand Clinical Trial Registry ACTRN12614000916640; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366691

PURPOSE Left ventricular assist devices (LVAD) are associated with an increased aerobic capacity in patients with chronic heart failure (CHF). However, studies evaluating the impact of LVAD implantation on physical activity (PA) are lacking. The aim of this study was to compare daily PA levels in participants with LVAD with well-matched CHF participants. METHODS Sixteen participants with an LVAD (age, 59.1 ± 10.8 yr) were case-matched to 16 participants with advanced CHF (age, 58.3 ± 8.7 yr), who were listed or being considered for cardiac transplantation. Participants underwent a cardiopulmonary exercise test to determine peak oxygen consumption (V˙O2 peak). Physical activity was monitored continuously for seven consecutive days with an Actiheart monitor. RESULTS V˙O2 peak in the CHF group (12.3 ± 3.5 mL·kg·min) was not significantly different to the LVAD group before LVAD implantation (10.4 ± 2.1 mL·kg·min), but was lower than in the LVAD group after implantation (15.8 ± 4.3 mL·kg·min; P < 0.05). Physical activity was higher in the LVAD (19.7 ± 6.4 kJ·kg·d) compared with the CHF group (11.6 ± 6.9 kJ·kg·d; P = 0.001). The LVAD participants spent more time performing moderate-intensity PA than their CHF counterparts (median, 26 min·d; interquartile range, 24-40 min·d vs median, 12 min·d; interquartile range, 9-16 min·d; P < 0.001). Physical activity was correlated with V˙O2 peak (r = 0.582; P = 0.001) across participants in the CHF and LVAD groups. CONCLUSIONS Higher levels of PA were observed in participants with LVAD compared with patients with advanced CHF. This may be due to a higher V˙O2 peak, resulting in an improved capacity to perform activities of daily living with less symptoms.

Insufficient crown height space, particularly in the interforaminal region of edentulous ridges with knife-edge morphology, may prevent successful prosthetic rehabilitation. Such conditions require osteoplasty, which might complicate computer-guided implant placement. This clinical report illustrates the treatment of a patient with complete edentulism rehabilitated with a mandibular implant-supported fixed dental prosthesis by using a virtually guided approach. Both alveolar ridge reduction and prosthetically driven implant insertions were computer-guided by surgical stents to increase accuracy and predictability. This approach enabled the immediate loading of the implants with an interim prosthesis before the delivery of a definitive screw-retained fixed prosthesis. At the 1-year follow-up visit, clinical and radiographic examination revealed a stable outcome.