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Purpose: Data on the prognostic impact of the micropapillary component in breast cancer are limited. The purpose of this study was to investigate the clinicopathological characteristics and long-term outcomes of pure and mixed invasive micropapillary breast cancer (IMPC) patients compared to invasive ductal cancer (IDC) patients., Methods: This retrospective study analysed all IMPC and IDC patients treated at the European Institute of Oncology (IEO) between 1997 and 2019. The overall cohort of IMPC patients was divided in two groups, pure and mixed IMPC. Each patient with mixed or pure IMPC was matched with one patient with IDC, based on year of surgery, age, pT, pN, and molecular subtype., Results: A total of 30,115 IDC, 120 pure IMPC and 150 mixed IMPC patients were considered eligible. Compared to IDC, pure and mixed IMPC patients presented a higher rate of locally advanced disease (pT2-T3, pN2-N3), vascular invasion, and Luminal B subtype. After matching, pure and mixed IMPC showed a significant higher rate of vascular invasion compared to IDC patients (p < 0.001). Invasive disease-free survival was better in IDC compared to pure IMPC patients (p = 0.11). Long-term overall survival was significantly worse in pure IMPC group compared to IDC group (p = 0.004), being instead similar between mixed IMPC vs matched IDC (p = 0.07)., Conclusion: These real-world data reported the worse prognosis of pure IMPC compared to IDC, highlighting the peculiar prognostic value of the micropapillary subtype itself in the decision-making process of IMPC management. An accurate pre-surgical diagnostic evaluation and a multidisciplinary approach are pivotal to best personalize its treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To evaluate the reliability of the Deauville score (DS) in therapy response assessment and to define the prognostic value of the metabolic response of end of induction (EOI) [ 18 F]FDG PET (PET) in follicular lymphoma patients., Methods: Adult patients with untreated grade 1-3a FL/ stage II-IV enrolled in the multicentre, prospective, phase III FOLL12 trial (NCT02063685) were randomized to receive standard immunochemotherapy followed by rituximab maintenance (standard arm) versus standard immunochemotherapy followed by response-adapted post-induction management (experimental arm). Baseline and EOI PET were mandatory for the study. All PET scans were centralized on the WIDEN® platform and classified according to DS in a blind independent central review. DS1-3 was considered negative (CMR), whereas DS4-5 was considered positive (not CMR). The primary endpoint was PFS. The main secondary endpoint was overall survival (OS)., Results: Overall, 807 follicular lymphoma patients-52% women, 89% stage III-IV disease, 40% with a high-risk FLIPI-2 score (3-5)-were enrolled in the study; 729 (90.4%) baseline and EOI PET were available for the analysis. EOI PET was positive (DS4-5) in 88/729 (12.1%) cases. Overall inter-reviewer agreement on PET pos/neg result was 0.92, while agreement on positive and negative cases was 0.77 and 0.94, respectively. The median follow-up was 69 months; 247 events were registered in the 5-yr follow-up, with a 5-yr PFS of 67% (95%CI: 63%-70%). The 5-yr PFS rate for PET neg (DS1-3) and PET pos (DS4-5) patients was 71% (95%CI: 67%-75%) and 36% (95%CI: 25%-46%), respectively, with HR 3.49 (95%CI: 2.57-4.72). Five-year PFS was worse as DS increased, with 74% (70%-78%), 58% (48%-67%; HR 1.71; p = 0.001)] and 36% (25%-46%; HR 3.88; p < 0.001) in DS1-2, DS3 and DS4-5, respectively. EOI PET maintained its prognostic value in both the standard and experimental arms. In the whole population, 5-yr OS was 94% (95%CI: 92%-96%), with 96% (95%CI: 94-97) and 82% (95%CI: 72%-89%) in EOI PET negative (DS1-3) and positive (DS4-5), respectively (HR 4.48; p < 0.001). When DS was associated with FLIPI-2, patients with DS3 or DS1-2 with high FLIPI-2 (3-5) experienced worse OS than patients with DS1-2 and low FLIPI-2 (1-2) (p = 0.003)., Conclusion: This study shows that DS is a reliable prognostic tool to evaluate EOI PET in follicular lymphoma patients, with prognostic value maintained both in the standard and experimental arms, making metabolic imaging a robust tool to assess response in FL. Moreover, although preliminary, this study provides further information on DS3 patients, who are considered as CMR but show a less favourable PFS than DS1-2 patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Symptoms of fibromyalgia (FM) fluctuate and vary in severity. The current study aimed to evaluate the efficacy of palmitoylethanolamide (PEA) and acetyl-L-carnitine (ALC) in FM patients over a 24-month period and to investigate the mediating function of pain catastrophizing subdomains in unfavorable relationships with disease severity levels in patients with FM. Patients were evaluated at baseline, after 12 months, and after 24 months, using different patient-reported measures (FIQR, FASmod, PSD, and PCS) to distinguish different levels of FM disease severity. A reduction of 30% or more from baseline was considered clinically important ("markedly improved"). A multivariate analysis was performed to identify the variables predictive of an FIQR reduction. Twenty-two patients (28.6%) were classified as "markedly improved", 16 patients (20.8%) as "slightly/moderately improved", and 39 patients (50.6%) as "not improved." The FIQR, FASmod, and PSD scores were significantly reduced at 24 months. The pain magnification domain score of the PCS was the only variable predictive of worse FIQR scores (Wald coefficient: -2.94; p = 0.047). These results suggest a potential long-term therapeutic role for the PEA + ALC combination, with pain magnification being the primary predictor of poor efficacy., Competing Interests: The authors declare no conflicts of interest.

In this work, core and core-shell microparticles formed by Ni-Mn-Co oxides with controlled composition were fabricated by an oxalate-assisted co-precipitation route, and their properties were analysed by diverse microscopy and spectroscopy techniques. The microparticles exhibit dimensions within the 2-6 μm range and mainly consist of NiO and NiMn 2 O 4 , the latter being promoted as the temperature of the treatment increases, especially in the shell region of the microparticles. Aspects such as the shell dimensions, the vibrational modes of the spinel compounds primarily observed in the shell region, the oxidation states of the cations at the surface of the microparticles, and the achievement of a Ni-rich 811 core and a Mn-rich 631 shell were thoroughly evaluated and discussed in this work.

Objectives: To evaluate the impact of the diagnostic delay on fibromyalgia (FM) severity., Methods: Data were retrospectively extracted from a large database of patients with FM belonging to the Italian Fibromyalgia Registry (IFR) residents on the Marche Region. The diagnosis of FM was formulated according to the 2016 American College of Rheumatology (ACR) criteria. The following information was obtained: time to diagnosis [categorised in early diagnosis (ED) if FM diagnosed within one year, late diagnosis (LD) if FM diagnosed more than 1 year but less than 5 years, and very late diagnosis (VLD) if FM diagnosed over 5 years from symptoms onset], revised Fibromyalgia Impact Questionnaire (FIQR), modified Fibromyalgia Assessment Status (FASmod), and Polysymptomatic Distress Scale (PDS) [consisting of the sum of Widespread Pain Index (WPI) and Symptom Severity Scale (SSS)]., Results: The study included 616 FM patients (92.2% female), with a mean disease duration of 6.46 (SD 4.14) years and a mean (SD) time to diagnosis of 3.45 (2.39) years. The ED group included 169 patients, the LD 320 patients, and the VLD 127 patients. Comparing the differences among groups, a significant difference in disease severity was observed in all the clinimetric indices in increasing the time to reach the diagnosis (p=0.000001): the median PDS scores were 13.36 (interquartile range [IQR] 7.00-20.00), 16.09 (IQR 9.00-22.00), and 23.00 (IQR 18.25-26.00) for ED, LD, and VLD, respectively., Conclusions: Delayed diagnosis is associated with poorer patient outcomes, including worsening severity.

Invasive lobular cancer (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast malignancies. The distinctive biological features of ILC include the loss of the cell adhesion molecule E-cadherin, which drives the tumor's peculiar discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, such tumors originate in the lobules, are more commonly bilateral compared to invasive ductal cancer (IDC) and require a more accurate diagnostic examination through imaging. They are luminal in molecular subtype, and exhibit estrogen and progesterone receptor positivity and HER2 negativity, thus presenting a more unpredictable response to neoadjuvant therapies. There has been a significant increase in research focused on this distinctive breast cancer subtype, including studies on its pathology, its clinical and surgical management, and the high-resolution definition of its genomic profile, as well as the development of new therapeutic perspectives. This review will summarize the heterogeneous pattern of this unique disease, focusing on challenges in its comprehensive clinical management and on future insights and research objectives., Competing Interests: Declaration of competing interest No financial/personal interest from all Authors with the exception of Prof. Giuseppe Curigliano., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hepatitis C virus (HCV)-associated diffuse large B-cell lymphoma (DLBCL) displays peculiar clinicopathological characteristics, but its molecular landscape is not fully elucidated. In this study, we investigated the clinicopathological and molecular features of 54 patients with HCV-associated DLBCL. The median age was 71 years. An underlying marginal zone lymphoma component was detected in 14.8% of cases. FISH analysis showed rearrangements involving BCL6 in 50.9% of cases, MYC in 11.3% and BCL2 in 3.7%. Lymph2Cx-based assay was successful in 38 cases, recognizing 16 cases (42.1%) as ABC and 16 cases as GCB subtypes, while six resulted unclassified. ABC cases exhibited a higher lymphoma-related mortality (LRM). Next-generation sequencing analysis showed mutations in 158/184 evaluated genes. The most frequently mutated genes were KMT2D (42.6%), SETD1B (33.3%), RERE (29.4%), FAS and PIM1 (27.8%) and TBL1XR1 (25.9%). A mutation in the NOTCH pathway was detected in 25.9% of cases and was associated with worst LRM. Cluster analysis by LymphGen classified 29/54 cases within definite groups, including BN2 in 14 (48.2%), ST2 in seven (24.2%) and MCD and EZB in four each (13.8%). Overall, these results indicate a preferential marginal zone origin for a consistent subgroup of HCV-associated DLBCL cases and suggest potential implications for molecularly targeted therapies., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Fibromyalgia (FM) remains a condition with a pathogenesis that is not completely understood, affecting a significant portion of the global population. This article summarises the main advances in FM during the last year. Even in 2023, research on FM was notably active. From a clinimetric perspective, studies have been conducted to evaluate the possibilities of interchanging the primary indices of disease severity, primarily for studies with substantial case numbers. Regarding FM pathogenesis, ongoing research focuses on small fiber neuropathy: some studies have documented its association with central sensitisation, while others have revealed distinct sensory profiles in patients with FM and small fiber neuropathy compared to those solely with small fiber neuropathy. Dorsal root ganglia seem to play a crucial role in the pathogenesis of FM as they host satellite glial cells, which are targeted by pain-driving immunoglobulin G. These antibodies have been identified in a subset of patients exhibiting high symptom severity. An important study conducted on animal models confirmed the role of neuroinflammation at the level of dorsal root ganglia, in this case mediated by polymorphonuclear neutrophils. Mounting evidence underscores the link between COVID-19 and the persistence of FM symptoms after recovery. In identifying potential biomarkers aiding FM diagnosis, research has also concentrated on studying the expression of specific circulating microRNAs. Recent discoveries have unveiled novel therapeutic strategies for FM, especially focused in non-pharmacological interventions. This includes a focus on non-invasive brain stimulation and exercise programs, all directed towards relieving symptoms and improving functionality in individuals affected by the condition.

Background: The use of scapular tip chimeric free flaps (STFFs) for reconstructing mandibular defects has recently become popular, but its utility relative to other bone-containing free flaps remains debatable. The aim of the report is to describe how technical modification of STFF impacted in its use for mandibular reconstruction also commenting results obtained in a unicentric series of patients., Patients and Methods: Patients undergoing mandibular reconstruction using an STFF from January 1, 2014 to June 1, 2022 were retrospectively enrolled in this report. We collected data on chimeric flap type, bone management, vascular pedicles, and the final outcomes. In total, 31 patients (13 men and 18 women) with a mean age of 68 years were enrolled. According to the classification system of Urken, 15 patients had body defects, while 7 had ramus defects, another 7 had symphysis defects, and 2 had both ramus and bodily defects. STFF was always harvested working in two equips simultaneously, in supine position. Dissection included preparation of chimeric components of the flap as latissimus dorsi, serratus and scapular tip. After pedicle dissection scapular bone was cut basing on reconstructive needing with a rectangular (stick) shape including the border of the scapula. In cases of longer bone harvesting, circumflex pedicle was also included to perfuse the upper portion of the scapular border. In five cases, the STFF was harvested with only the scapular angle component, and was thus a composite osteomuscular flap; for the remaining 26 cases, a chimeric STFF was used. Circumflex pedicle was included for eight patients. Six of the seven patients with symphyseal defects underwent a single osteotomy., Results: The average length of the harvested was 69.92 mm (maximum length = 104 mm). The average height of transplanted bone was 26.78 mm (maximum height = 44.2 mm). Mouth-opening was normal in 25 patients, limited in 6 patients, and severely impaired in no patients. The cosmetic results were rated as excellent by 20 patients, good by 8 patients, and poor by 3 patients., Conclusion: The STFF is an excellent option for mandibular reconstruction when other flaps are not available and for patients in poor general condition. Technical innovations here presented made possible to harvest long bone segments with accurate shape thanks to osteotomies if needed and with adequate soft tissues components of the chimeric flap, ensuring satisfactory functional and cosmetic results., (© 2024 Wiley Periodicals LLC.)

A breast unit is a multidisciplinary center specialized in the management of women with breast diseases, including breast cancer (BC). It represents a care path, passing from screening activities to diagnostic investigations, from surgery to the definition of the therapeutic strategy, from psychophysical rehabilitation to long-term checks (follow-up), and up to genetic counseling. Since 2006, following a resolution issued by the European Parliament to urge member states to activate multidisciplinary breast centers by 2016, work has been underway throughout Italy to improve the management of women with BC. In Italy, the State-Regions agreement was signed on 18 December 2014, sanctioning the establishment of breast units. These centers must adhere to specific quality criteria and requirements. In 2020, the experts of the EUSOMA group (European Society of Breast Cancer Specialists), in their latest document published, expanded the requirements of the breast units. Furthermore, Senonetwork was founded in 2012 with the aim of allowing BC to be treated in breast units that comply with European requirements to ensure equal treatment opportunities for all Italian women. Indeed, the available data indicate that the BC patient has a greater chance of better treatment in the breast units with a multidisciplinary team, thus increasing the survival rate with a better quality of life, compared to those managed in nonspecialized structures. The present review is a perspective on the current Italian reality of breast units, updated with the available literature and the most recent epidemiological data from Senonetwork and AgeNaS., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Zn 2 GeO 4 is considered a very promising alternative to current luminescent semiconductors. Previous results suggest that its emitted wavelength may depend on different variables, such as particle size and morphology, among others. In this work, we have prepared pure and highly homogeneous Zn 2 GeO 4 nanorods under hydrothermal synthesis conditions with a willemite-like structure. Their luminescent properties have been explored and their band gap is estimated, which are distinct from those of previously reported Zn 2 GeO 4 bulk particles. Therefore, our results identify particle morphology as a crucial factor for maximizing and fine-tuning the luminescence of Zn 2 GeO 4 nano-phosphors., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Abemaciclib is currently approved for the adjuvant treatment of high-risk, lymph node (LN)-positive, hormone receptor (HR)-positive breast cancer (BC). In a real-world setting the clinicopathologic features of patients potentially eligible for adjuvant abemaciclib remain to be defined. There are conflicting data regarding the biological behavior and long-term outcomes across invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). In our study we retrospectively assessed the real-world data and long-term outcome of selected high-risk features ILC compared to IDC, according to the MonarchE trial inclusion criteria., Methods: We identified 15,071 patients who got surgery at the European Institute of Oncology for a first primary, non-metastatic, HR-positive, HER2-negative BC from 2000 to 2008. 11,981 (79.5%) patients had an IDC and 1524 (10.1%) an ILC. The remaining 1566 patients (10.4%) had either combined ductal and lobular breast cancer or another histological breast cancer subtype. According to the eligibility criteria of the MonarchE study, we identified two high-risk groups, based on high number of positive lymph nodes, large tumor size, or a high cellular proliferation as measured by tumor grade or biomarkers. Patients were matched by propensity score., Findings: A total of 2872 (21.3%) patients were selected as clinically high-risk, including 361/1524 ILC (23.7%) and 2511/11,981 IDC (21%). 322 high-risk ILC were matched with similar high-risk IDC. The median follow-up was 13.2 years for survival. In the matched set, invasive disease-free survival (IDFS) (log-rank P = 0.09) and overall survival (OS) (log-rank P = 0.48) were not statistically significantly different between the two histological groups. For IDC patients, the 5-year and 10-year IDFS rates (95% CI) were 77.7% (72.9-82.2) and 57.3% (51.7-63.1) respectively, compared to the 5-year and 10-year IDFS rates of ILC patients that were 75.5% (70.6-80.2) and 50.7% (45.0-56.6). The 5-year and 10-year distant relapse free survival (DRFS) rates were 80% (75.3-84.2) and 65.3% (59.8-70.7) in IDC cohort, compared to the 5-year and the 10-year DRFS rates of 78.7% (74.0-83.1) and 61.5% (55.9-67.1) in the ILC cohort. Such data match the recent outcomes efficacy results of the MonarchE control arm. More patients in the ILC (n = 17) than in the IDC group (n = 10) developed axillary recurrence. At multivariable analysis, stratified for specific clinical features, age <35 years, pT2-3, axillary involvement with more than 10 positive axillary nodes were found to be predictors of unfavorable IDFS and OS in the overall matched high-risk population., Interpretation: Findings from this matched cohort study reported similar IDFS and DRFS rates for high risk HR positive early BC when compared to the control arm overall IDFS and DRFS rates reported from the MonarchE trial. Our study demonstrated rates of concordant long-term outcome status beyond histologic subtype. These data support an escalation strategy for these two different histological entities when diagnosed with high-risk features. In our dataset approximately 21% rate of high-risk HR positive early BC patients are potentially eligible for adjuvant abemaciclib treatment., Funding: Umberto Veronesi Foundation., Competing Interests: Prof. Giuseppe Curigliano: Grants or contracts from any entity: Merck; Consulting fees: BMS, Roche, Pfizer, Novartis, Lilly, Astra Zeneca, Daichii Sankyo, Merck, Seagen, Ellipsis, Gilead, Menarini; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Lilly, Pfizer, Relay, Gilead, Novartis; Support for attending meetings and/or travel: Daichii Sankyo. Dr. Emilia Montagna: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Novartis., (© 2024 The Authors.)

This paper outlines the design, characterization, and validation of a novel wearable haptic device capable of delivering skin stretch, force feedback, or a combination of both, to the user's arm. In this study, we conducted physical and perceptual characterization with eleven able-bodied participants, and two separate experiments involving discrimination and manipulation tasks, encompassing a total of 32 participants. In both experiments, we used the CUFF device in conjunction with the Pisa/IIT SoftHand. The first experiment was a discrimination task in which participants were required to differentiate between pairs of cylinders based on their dimensions and perceived softness. The second experiment called for participants to control the robotic hand in order to grasp objects. Following the experiments, participants provided a subjective evaluation of the device. The results from the experiments and the participants' feedback underscored the effectiveness of the proposed device. Thanks to its versatility and structural design, the device shows promise as a viable solution for a variety of applications, including teleoperation, guidance, rehabilitation tasks, and prosthetic applications.

Purpose: Aplasia cutis congenita (ACC) is a heterogeneous group of congenital disorders characterized by the absence of epidermis, dermis, appendages, subcutaneous tissue, and bone. The aim of the study is to describe a clinical report of ACC of the scalp treated with skin expanders., Clinical Report: In October 2019, a 16-year-old female patient underwent scalp expansion with 2 rectangular devices (150 and 250 cm3; Radovan Mentor-Johnson&Johnson). The inflation started 30 days after surgery and continued once every 7 to 10 days to gain 10% of overexpansion. After 3 months, the patient underwent the second surgical step with the expanded scalp transposed to close the defect. Clinical examination 6 months after surgery revealed an acceptable cosmetic result with a hidden surgical scar and hair growth in the previous area of frontoparietal alopecia., Conclusion: Skin expander for the reconstruction of extensive ACC defects of the scalp is a valid procedure., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Objectives: The persistence in therapy of rheumatoid arthritis drugs and particularly bDMARD is a limiting factor for their long-term use. The randomized controlled trials (RCTs) may not reflect real-world contexts due to strict inclusion and exclusion criteria. Baricitinib, which targets both JAK1 and JAK2, has been used in Italy for several years. The aim of this multi-center study is to assess the real world persistence on therapy of baricitinib in RA patients and to identify predictive factors of baricitinib's survival rate., Methods: This is a retrospective, multicentric, Italian, longitudinal study. All patients were enrolled according to the following criteria: a) age ≥ 18 years old; b) diagnosed with RA according 2010 ACR/EULAR classification criteria; c) treated with baricitinib. In order to describe baricitinib clinical efficacy, the survival rate was evaluated by The Kaplan-Meier curve. Then, predictive factors of drug retention rate were assessed by performing the Cox analysis, identifying which risk factors influenced treatment persistence., Results: Overall, we included 478 patients treated with baricitinib. Among them, 380 (79.5%) were females. Baricitinib's survival rate was 94.6% at 6 months, 87.9% at 12 months, 81.7% at 24 months and 53.4% at 48 months. The Cox analysis regression showed that a higher bDMARDs/tsDMARD line of therapy seems to be a negative prognostic factor for the drug retention rate (HR 1.26 CI 95% 1.07-1.49, p = 0.006., Conclusion: Real-life study confirms baricitinib effectiveness up to 4 years, but previous treatment with bDMARDs was a negative prognostic factor for its survival rate., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: To investigate the prevalence of central sensitization (CS) in patients with psoriatic arthritis (PsA) and its association with disease activity and patient-reported outcome measures., Methods: This cross-sectional study included adults with PsA without coexisting fibromyalgia (FM). Patients underwent a clinimetric assessment to collect variables regarding disease activity, quality of life (QOL), functional ability, impact of disease, and CS. Spearman ρ was used to examine the relationship between CS Inventory (CSI) scores and other variables. A multivariate analysis was performed to determine the independent contribution of each variable to the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) score., Results: One hundred fifty-seven patients were enrolled. Of them, 45.2% scored a CSI ≥ 40, indicating a high probability of CS. Significant correlations were found between CSI and disease activity, as evaluated by Disease Activity in Psoriatic Arthritis score and Psoriatic Arthritis Disease Activity Score (ρ 0.587 and ρ 0.573, respectively), between CSI and the Health Assessment Questionnaire (ρ 0.607), and between CSI and the 36-item Short Form Health Survey physical component summary and mental component summary scores (ρ -0.405 and ρ -0.483, respectively). In multivariate analysis, CSI score was the principal independent variable ( P < 0.001) contributing to PsAID-12 score., Conclusion: Patients with PsA with symptoms of CS had higher disease activity, worse functional ability, and worse QOL. The presence of CS is the major contributor in the impact of disease., (Copyright © 2024 by the Journal of Rheumatology.)