Altered processing of conflicting body representations in women with restrictive anorexia nervosa.

Cognitive and affective impairments in processing body image have been observed in patients with Anorexia Nervosa (AN) and may induce the hypercontrolled and regulative behaviors observed in this disorder. Here, we aimed to probe the link between activation of body representations and cognitive control by investigating the ability to resolve body-related representational conflicts in women with restrictive AN and matched healthy controls (HC). Participants performed a modified version of the Flanker task in which underweight and overweight body images were presented as targets and distractors; a classic version of the task, with letters, was also administered as a control. The findings indicated that performance was better among the HC group in the task with bodies compared to the task with letters; however, no such facilitation was observed in AN patients, whose overall performance was poorer than that of the HC group in both tasks. In the task with body stimuli, performance among patients with AN was the worst on trials presenting underweight targets with overweight bodies as flankers. These results may reflect a dysfunctional association between the processing of body-related representations and cognitive control mechanisms that may aid clinicians in the development of optimal individualized treatments.

SFE-AFCE-SFMN 2022 consensus on the management of thyroid nodules: Synthesis and algorithms.

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid with benign and non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies, the French Society of Endocrinology (SFE), the French Association of Endocrine Surgery (AFCE) and the French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This specific text is a summary chapter taking up the recommendations from specific sections and presenting algorithms for the exploration and management of thyroid nodules.

SFE-AFCE-SFMN 2022 Consensus on the management of thyroid nodules : Recommendations in thyroid cytology: from technique to interpretation.

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with the technique and interpretation of thyroid fine-needle aspiration biopsy (FNAB), a reference test for the analysis of thyroid nodules.

Delayed intracranial hemorrhage after mild traumatic brain injury in patients on oral anticoagulants: is the juice worth the squeeze?

OBJECTIVE: Mild Traumatic Brain Injury (MTBI) in anticoagulated patients is a common challenge for Emergency Department (ED) Physicians. Anticoagulation is considered a risk factor for developing delayed intracranial hemorrhage (ICH) after MTBI. The occurrence of this event in patients on Vitamin K Antagonists (VKA) or Direct Oral Anticoagulants (DOACs) remains unclear. Primary endpoint: to analyze the role of anticoagulants as risk factors for developing delayed ICH after MTBI and evaluate the indications to repeat a cranial computed tomography (CT) after a period of observation. Secondary endpoint: to assess the difference in the prevalence rate of delayed ICH in patients on VKA versus those on DOACs. PATIENTS AND METHODS: We evaluated all consecutive patients admitted to our ED for MTBI, which had a control CT for late ICH after a negative CT at admission. We used a propensity score match (PSM) on factors affecting the need for oral anticoagulation to adjust the comparison between anticoagulated vs. non-anticoagulated patients for the baseline clinical characteristics. RESULTS: Among 685 patients enrolled, 15 (2.2%) developed ICH at control CT. After PSM, the incidence of ICH, although slightly higher, was not statistically different in anticoagulated patients vs. non-anticoagulated (2.3% vs. 0.6%, p=0.371). Among the 111 patients on VKA, 5 (4.5%) had a late ICH, compared to 4 out of 99 (4.0%) on DOACs; the difference was not statistically significant (p=0.868). CONCLUSIONS: The risk of developing delayed ICH after MTBI in patients on anticoagulation therapy is low. After correction for baseline covariates, the risk does not appear higher compared to non-anticoagulated patients. Thus, a routine control CT scan seems advisable only for patients presenting a clinical deterioration. Larger, prospective trials are required to clarify the safety profile of DOACs vs. VKA in MTBI.

Protective effects induced by the food supplement Fluxonorm® in the lower urinary tract.

OBJECTIVE: Fluxonorm® is a dietary supplement that includes water-soluble extracts of Solidago virga-aurea, Phyllantus niruri, Epilobium angustifolium, Peumus boldus and Ononis spinosa. The aim of the present study was to evaluate the tolerability and efficacy of Fluxonorm® in improving lower urinary tract symptoms in patients with benign prostatic hyperplasia (BPH) in combination with standard of care. PATIENTS AND METHODS: Lower urinary tract symptoms can be improved by a marked anti-inflammatory action on the lower urinary tract (irritative symptoms) and/or by an anti-proliferative action (obstructive symptoms) on the prostate. Thirty patients were enrolled to evaluate the effect of Fluxonorm® on improving lower urinary tract symptoms. All patients complained of lower urinary tract symptoms (LUTS), such as hesitancy, poor flow, intermittent flow, incomplete voiding (obstructive symptoms), as well as increased frequency, nocturia and urgency (storage symptoms). All patients were treated with one tablet of Fluxonorm® (1200 mg) daily for 30 days to corroborate the results of our observation in which the food supplement (800 µg/mL) was also studied on the human prostate cancer PC3 cell line (antiproliferative activity) and on prostaglandin (PG)E2 production (anti-inflammatory activity). In addition, the effect of this compound on cyclooxygenase-2 (COX-2) gene expression was investigated. Finally, a bioinformatic analysis was conducted with the aim of unravelling the mechanism of action underlying the observed bio-pharmacological effects. RESULTS: As hypothesized in our preclinical research, adding Fluxonorm® to the therapy of enrolled patients improved all studied clinical parameters, including maximum flow (Qmax), after one month of treatment. In the preclinical evaluation, this formulation reduced PC3 cell viability and PGE2 production. The effects were also paralleled by reduced COX-2 gene expression and Fluxonorm®'s partly related content of catechin. While docking studies pointed out to the putative inhibition of matrix metalloproteinse-2 by gallic acid, as a further mechanism underlying the observed anti-proliferative effects, in PC3 cells exposed to Fluxonorm®. CONCLUSIONS: Fluxonorm® improved the efficacy of standard therapy, in terms of antioxidant/anti-inflammatory effects, for the management of lower urinary tract symptoms (LUTS). This could be related, albeit partially, to the blunting effect of this compound on PGE2 production.

Daratumumab in multiple myeloma: experience of the multiple myeloma GIMEMA Lazio group.

Daratumumab (DARA) is a human IgG-K monoclonal antibody (MoAb) targeting CD38 that is approved alone or in combination with bortezomib and dexamethasone or lenalidomide and dexamethasone for relapsed or refractory MM (RRMM) in patients previously exposed or double refractory to proteasome inhibitors (PI) and immunomodulatory drugs (IMiDs). However, there are limited data on its clinical activity and tolerability in real-world patients. Therefore, in the present study, we aim to determine the efficacy and toxicity profile of daratumumab in a real-life setting. In this study, we report the experience of the multiple myeloma GIMEMA Lazio Group in 62 relapsed/refractory MM patients treated with daratumumab as monotherapy who had previously received at least two treatment lines including a PI and an IMiDs or had been double refractory. Patients received DARA 16 mg/kg intravenously weekly for 8 weeks, every 2 weeks for 16 weeks, and every 4 weeks until disease progression or unacceptable toxicity. The overall response rate to daratumumab was 46%. Median progression-free survival (PFS) and overall survival reached 2.7 and 22.4 months, respectively. DARA was generally well tolerated; however, 2 patients interrupted their therapy due to adverse events. Present real-life experience confirms that DARA monotherapy is an effective strategy for heavily pre-treated and refractory patients with multiple myeloma, with a favorable safety profile.

Alkaline phosphatase (alp) levels in multiple myeloma and solid cancers with bone lesions: Is there any difference?

INTRODUCTION: Bone involvement in Multiple Myeloma results from increased osteoclast formation and activity that occurs in proximity to myeloma cells. The role of Alkaline Phosphatse (ALP) in this process and the diagnostic significance of plasma levels in patients with MM are unclear. AIM: To compare plasma ALP levels in patients with MM and solid cancers and metastatic lesions to the bone. RESULTS: In this observational retrospective study we enrolled 901 patients were enrolled: 440 patients (49%) with Multiple Myeloma, 461 (51%) with solid cancers. All 901 patients had bone lesions. Among patients with Multiple Myeloma, ALP values were mainly in the range of normality than those observed in patients with solid cancers and bone lesions. This difference is independent of stage, number and type of bone lesions. CONCLUSION: This study suggests that plasma ALP has a different clinical significance in MM than in other neoplasms and could be used as a discriminating marker in presence of bone lesions. In particular, lower or normal values, should suggest further investigations such as urinary and serum electrophoresis, associated with bone marrow aspirate in case of the presence of a monoclonal component, in order to confirm or exclude a MM diagnosis.

Wellens Syndrome without chest pain, is it possible?

OBJECTIVE: Wellens syndrome is a typical electrocardiographic and clinical pattern that correlates with a severe proximal stenosis of the left anterior descending artery (LAD). It is associated with previous angina, no or slightly increased cardiac markers, and two ECG patterns: diphasic T wave in V2-V3 (Type A) or deep negative T waves from V1 to V4 (type B). In this paper, we described two cases with asymptomatic Wellens patterns. PATIENTS AND METHODS: We describe two cases of Wellens syndrome ECG pattern that we observed in our Emergency Department not accompanied by chest pain or angina equivalents. RESULTS: Both patients presented significant stenosis of LAD at the coronary angiography. CONCLUSIONS: Asymptomatic patients presenting with Wellens ECG pattern should perform a coronary arteriography cause of the risk of a severe LAD stenosis. We need further studies to confirm if all "silent" Wellens syndromes deserve angiographic study.

Unexpected macrophage activation syndrome in a healthy young woman: a case report.

Macrophage activation syndrome (MAS) is a life-threatening condition and a medical emergency with a high-risk of mortality. It belongs to a group of diseases known as "hemophagocytic lymphohistiocytosis", characterized by a cytokine storm, with secretion of tumor necrosis factor, interleukins and interferon-gamma, and an inappropriate activation of macrophages and T-lymphocytes. Some inflammatory and systemic autoimmune diseases, such as systemic juvenile idiopathic arthritis, Still's disease and systemic lupus erythematosus, can develop into macrophage activation syndrome. This is the first episode of macrophage activation syndrome (MAS) in a young healthy woman. She arrived at the Emergency Department complaining of four days of weakness and fever not responsive to paracetamol. She had no significant past medical history, her mother suffered from rheumatoid arthritis. In the Emergency Department, we performed laboratory exams, autoimmune and infectious disease screening, bone marrow biopsy. The final diagnosis was of macrophage activation syndrome. Macrophage activation syndrome, in extremely rare cases, can arise independently years before the manifestation of an autoimmune disease. Persistent fever, high level of inflammatory markers and pancytopenia should raise suspicion in healthy people, especially when associated with a family history of autoimmune disease. Early diagnosis and consequent early treatment are fundamental to avoid progressive tissue damage that can lead to organ failure and death.

A novel method for calculating beta band burst durations in Parkinson's disease using a physiological baseline.

BACKGROUND: Pathologically prolonged bursts of neural activity in the 8-30 Hz frequency range in Parkinson's disease have been measured using high power event detector thresholds. NEW METHOD: This study introduces a novel method for determining beta bursts using a power baseline based on spectral activity that overlapped a simulated 1/f spectrum. We used resting state local field potentials from people with Parkinson's disease and a simulated 1/f signal to measure beta burst durations, to demonstrate how tuning parameters (i.e., bandwidth and center frequency) affect burst durations, to compare burst duration distributions with high power threshold methods, and to study the effect of increasing neurostimulation intensities on burst duration. RESULTS: The baseline method captured a broad distribution of resting state beta band burst durations. Mean beta band burst durations were significantly shorter on compared to off neurostimulation (p = 0.0046), and their distribution shifted towards that of the 1/f spectrum during increasing intensities of stimulation. COMPARISON WITH EXISTING METHODS: High power event detection methods, measure duration of higher power bursts and omit portions of the neural signal. The baseline method captured the broadest distribution of burst durations and was more sensitive than high power detection methods in demonstrating the effect of neurostimulation on beta burst duration. CONCLUSIONS: The baseline method captured a broad range of fluctuations in beta band neural activity and demonstrated that subthalamic neurostimulation shortened burst durations in a dose (intensity) dependent manner, suggesting that beta burst duration is a useful control variable for closed loop algorithms.

Preoperative Role of RAS or BRAF K601E in the Guidance of Surgery for Indeterminate Thyroid Nodules.

BACKGROUND: RAS and K601E BRAF mutations are not a reliable indicator of malignancy in fine-needle aspirations (FNA) of thyroid indeterminate cytologic nodules. We aimed to evaluate the histologic characteristics, the risk of malignancy associated with such mutations in FNA and their potential interest for preoperative clinical management of nodules. METHODS: We evaluated 69 indeterminate thyroid nodules with RAS or K601E BRAF mutations with available histopathologic follow-up. All FNA specimens were indeterminate according to the thyroid Bethesda system. Diagnosis of malignant, benign or indolent neoplasms was classified according to 2017 WHO classification. Carcinoma, NIFTP (noninvasive follicular thyroid neoplasm with papillary-like features) and WDTUMP (well-differentiated tumor of uncertain malignant potential) were considered "surgical," as they require surgical excision. Adenoma was considered "non-surgical." The risk of malignancy and the risk of "surgical disease" were evaluated. RESULTS: Pathologic evaluation of the 69 mutated nodules demonstrated benign, indolent and malignant histology in 17 cases (25%), 21 cases (30%) and 31 cases (45%), respectively. The risk of malignancy was 45%, and the risk of surgical disease was 75%. The majority of carcinomas were a follicular variant of papillary thyroid carcinoma. On follow-up, there have been no recurrences to date. CONCLUSION: Preoperative RAS or BRAF K601E mutations detection in cytologic indeterminate thyroid nodules carries a high risk of surgical disease and may benefit from surgical management. Most surgical lesions harboring those mutations are low-risk tumors, which may be in favor of an initial lobectomy.

Magnesium sulphate in the Emergency Department: an old, new friend.

With our study, we searched the medical literature to find magnesium (Mg) correlation with Emergency situations or its use in Emergency Medicine. Our aim is to fill the gap that we find in our daily routine between Mg studies on its role in Emergency and the real conception that doctors have of it in medical practice. We searched the literature for terms as magnesium or magnesium sulphate, magnesium in emergency, eclampsia, arrhythmias, acute asthma exacerbation, magnesium, and pediatric population. After a thorough research, we divided our discoveries into chapters to sort out a large amount often discordant articles.

Expert Panel Consensus Statement for Proper Evaluation of First Relapse in Multiple Myeloma.

PURPOSE OF REVIEW: A working group of six expert physicians convened to assess the spectrum of multiple myeloma relapse presentations, discussed the features that can define the disease as aggressive and not aggressive, and established whether this information could help in selecting treatment together with the characteristics of disease and of patients and type of prior therapy. RECENT FINDINGS: The working group agreed that relapse should be distinguished between biochemical and clinical according to IMWG. Moreover, the expert panel defined "aggressive disease" as a clinical condition that requires therapy able to induce a rapid and as deep as possible response to release symptoms and to avoid impending danger of new events. According to this definition, relapse was considered aggressive if it presents with at least one of the following features: doubling of M protein rate over 2 months, renal insufficiency, hypercalcemia, extramedullary disease, elevated LDH, high plasma cell proliferative index, presence of plasma cells in peripheral blood, or skeletal-related complications. Moreover, the panel agreed that this classification can be useful to choose therapy in first relapse together with other patient, disease, and prior therapy characteristics. So, this item was included in a new therapeutic algorithm. The treatment choice in MM at relapse is wider than in the past with the availability of many new therapeutic regimens leading to increased diversity of approaches and relevant risk of inappropriate treatment decisions. A practical classification of relapses into aggressive or non-aggressive, included in a decisional algorithm on MM management at first relapse, could help to make the appropriate treatment decisions.

Phase 1/2 study of weekly carfilzomib, cyclophosphamide, dexamethasone in newly diagnosed transplant-ineligible myeloma.

This multicentre, open-label phase 1/2 trial determined safety and efficacy of weekly carfilzomib plus cyclophosphamide-dexamethasone (wKCyd) in newly diagnosed multiple myeloma (NDMM) patients aged ⩾65 years or transplant ineligible. Patients received wKCyd for up to nine 28-day cycles, followed by maintenance with carfilzomib until progression/intolerance. The phase 1 portion used a 3+3 dose-escalation scheme to determine the maximum tolerated dose of weekly carfilzomib: 12 patients received wKCyd with carfilzomib doses of 45, 56 and 70 mg/m2. The recommended phase 2 dose was established at 70 mg/m2 and 54 patients (phase 1 and 2) received weekly carfilzomib 70 mg/m2: 85% of them achieved ⩾partial response (PR), 66% ⩾very good PR, 30%⩾near-complete response (CR) and 15% CR. Responses improved in 40 patients who started maintenance: 98% achieved ⩾PR, including 29% CR and 10% stringent CR. After a median follow-up of 18 months, the 2-year progression-free survival and overall survival rates were 53.2% and 81%, respectively. The most frequent grade 3-5 toxicities were neutropenia (22%) and cardiopulmonary adverse events (9%). This is the first study of weekly carfilzomib plus an alkylating agent in elderly patients with NDMM. wKCyd was effective, with an acceptable risk/benefit ratio, and thus can be a valid option in this setting.

Molecular testing of BRAF, RAS and TERT on thyroid FNAs with indeterminate cytology improves diagnostic accuracy.

OBJECTIVE: Liquid-based (LB)-FNA is widely recognized as a reliable diagnostic method to evaluate thyroid nodules. However, up to 30% of LB-FNA remain indeterminate according to the Bethesda system. Use of molecular biomarkers has been recommended to improve its pathological accuracy but implementation of these tests in clinical practice may be difficult. Here, we evaluated feasibility and performance of molecular profiling in routine practice by testing LB-FNA for BRAF, N/HRAS and TERT mutations. METHODS: We studied a large prospective cohort of 326 cases, including 61 atypia of undetermined significance, 124 follicular neoplasms, 72 suspicious for malignancy and 69 malignant cases. Diagnosis of malignancy was confirmed by histology on paired surgical specimen. RESULTS: Mutated LB-FNAs were significantly associated with malignancy regardless of the cytological classification. Overall sensitivity was 60% and specificity 89%. Importantly, in atypia of undetermined significance and follicular neoplasm patients undergoing surgery according to the Bethesda guidelines, negative predictive values were 85.4% and 90% respectively. TERT promoter mutation was rare but very specific for malignancy (5.5%) suggesting that it could be of interest in patients with indeterminate cytology. CONCLUSIONS: Mutation profiling can be successfully performed on thyroid LB-FNA without any dedicated sample in a pathology laboratory. It is an easy way to improve diagnostic accuracy of routine LB-FNA and may help to better select patients for surgery and to avoid unnecessary thyroidectomies.

Prospective longitudinal study on quality of life in relapsed/refractory multiple myeloma patients receiving second- or third-line lenalidomide or bortezomib treatment.

Treatment advances for multiple myeloma (MM) that have prolonged survival emphasise the importance of measuring patients' health-related quality of life (HRQoL) in clinical studies. HRQoL/functioning and symptoms of patients with relapsed/refractory MM (RRMM) receiving second- or third-line lenalidomide or bortezomib treatment were measured in a prospective European multicentre, observational study at different time points. At baseline, patients in the lenalidomide cohort were frailer than in the bortezomib cohort with more rapid disease progression at study entry (more patients with Eastern Cooperative Oncology Group performance status >2, shorter time from diagnosis, more chronic heart failure, higher serum creatinine levels, more patients with dialysis required). About 40% of the patients receiving lenalidomide discontinued the study in <6 months while 55% in the bortezomib cohort discontinued. No substantial HRQoL deterioration was observed for the first 6 months in patients with RRMM receiving one or the other treatment. For patients still on treatment at study completion (month 6), only the European Organization for Research and Treatment of Cancer Quality-of-Life Core domains of Diarrhoea and Global Health Status/QoL had worsened in the lenalidomide and bortezomib cohorts, respectively. A clinically meaningful deterioration in HRQoL was more often observed for patients who discontinued the study prior to 6 months in the bortezomib cohort than in the lenalidomide cohort.

Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. SUBJECTS AND METHODS: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. RESULTS: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. CONCLUSIONS: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.