Cerebral Tumefactive Inflammatory Lesion Occurrence During Ixekizumab Treatment in a Patient With Active Psoriatic Arthritis.

INTRODUCTION: Ixekizumab is an anti-interleukin-17A (IL-17A) humanized monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis, active psoriatic arthritis, and ankylosing spondylitis. Central nervous system inflammatory manifestations are atypical during therapy with IL-17A inhibitors, with only one case of myelitis described to date. CASE REPORT: A 72-year-old man with a medical history of active psoriatic arthritis was admitted to our department owing to the acute onset of left face numbness 1 month after the first ixekizumab administration. Magnetic resonance imaging of the brain displayed a large T2-hyperintense infratentorial lesion involving the root of the fifth and seventh left cranial nerves. A thorough laboratoristic and instrumental work-up did not show elements suggestive of extracerebral neoplasms or infections. Therefore, neuronavigation-assisted brain biopsy was performed, and histologic analysis of the lesion revealed the presence of wide aggregates of foamy histiocytes diffusely infiltrating the brain parenchyma, in the absence of malignant tissue or histologic elements suggestive of central nervous system infections or primary histiocytoses. Steroid treatment (dexamethasone 8 mg/daily) was then administered with subsequent clinical amelioration. One month after hospital discharge, a brain magnetic resonance imaging showed a nearly complete resolution of the lesion. CONCLUSION: This is the first case of a cerebral inflammatory lesion occurring during treatment with ixekizumab. Although very rare, neurological complications may occur during anti-IL-17A therapies, thus leading to the need for careful monitoring of patients exposed to these drugs.

Eosinophilic granuloma of the calvarium: is conservative management a valid option? Illustrative case and systematic review of the literature.

INTRODUCTION: Eosinophilic granuloma (EG) is the most common form of Langerhans cell histiocytosis, presenting as a single osteolytic lesion of the calvarium. Its diagnosis is based on typical clinical and radiological features. While surgical resection has been the standard treatment for EG, growing evidence favors watchful waiting, as unifocal calvarial lesions appear to frequently undergo spontaneous remission. However, histopathological confirmations of this hypothesis are still very limited. METHODS: Methods. Here, we report a case of EG with typical clinical and radiological features which, due to intervening circumstances, was resected in a delayed fashion. Moreover, we perform a systematic review of the literature on conservative management of EG. RESULTS: In our case, histological examination showed ongoing bone regeneration with no traces of the disease. Through our literature review, we found 47 cases of calvarial EG managed with watchful waiting. No active intervention was required in 43 cases (91%). Four patients (9%) received surgery or chemotherapy due to the persistence/progression of symptoms or family request. Three reports other than ours documented spontaneous disease remission in surgically resected EG upon histopathological examination. CONCLUSION: Our report provides further evidence that watchful waiting can be a reasonable option in the management of single calvarial EG.

Effect of Radio-Chemotherapy on PD-L1 Immunohistochemical Expression in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Programmed death-ligand 1 (PD-L1) checkpoint inhibitors represent a mainstay of therapy in head and neck squamous cell cancer (HNSCC). However, little is known about the influence of combined therapy on PD-L1 expression. The study aims to gather evidence on this topic. METHODS: A systematic search was carried out in electronic databases Pubmed-MEDLINE and Embase to retrieve studies on the comparison of PD-L1 expression before and after conventional therapy. Data were extracted and a quantitative analysis with pooled odds ratios (ORs) was performed when applicable. RESULTS: Of 5688 items, 15 were finally included. Only a minority of studies assessed PD-L1 with the recommended combined positive score (CPS). The results are highly heterogeneous, with some studies reporting an increase in PD-L1 expression and others reporting a decrease. Three studies allowed for quantitative analysis and showed a pooled OR of 0.49 (CI 0.27-0.90). CONCLUSIONS: From the present evidence, a clear conclusion towards an increase or decrease in PD-L1 expression after combined therapy cannot be drawn, but even with few studies available, a trend towards an increase in expression in tumor cells at a cutoff of 1% can be noted in patients undergoing platinum-based therapy. Future studies will provide more robust data on the effect of combined therapy on PD-L1 expression.

Epidemiological trends and trajectories of MAFLD-associated hepatocellular carcinoma 2002-2033: the ITA.LI.CA database.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a new inclusive definition of the whole spectrum of liver diseases associated to metabolic disorders. The main objective of this study was to compare patients with MAFLD and non-MAFLD with hepatocellular carcinoma (HCC) included in a nationally representative cohort. METHODS: We analysed 6882 consecutive patients with HCC enrolled from 2002 to 2019 by 23 Italian Liver Cancer centres to compare epidemiological and future trends in three subgroups: pure, single aetiology MAFLD (S-MAFLD); mixed aetiology MAFLD (metabolic and others, M-MAFLD); and non-MAFLD HCC. RESULTS: MAFLD was diagnosed in the majority of patients with HCC (68.4%). The proportion of both total MAFLD and S-MAFLD HCC significantly increased over time (from 50.4% and 3.6% in 2002-2003, to 77.3% and 28.9% in 2018-2019, respectively, p<0.001). In Italy S-MAFLD HCC is expected to overcome M-MAFLD HCC in about 6 years. Patients with S-MAFLD HCC were older, more frequently men and less frequently cirrhotic with clinically relevant portal hypertension and a surveillance-related diagnosis. They had more frequently large tumours and extrahepatic metastases. After weighting, and compared with patients with non-MAFLD, S-MAFLD and M-MAFLD HCC showed a significantly lower overall (p=0.026, p=0.004) and HCC-related (p<0.001, for both) risk of death. Patients with S-MAFLD HCC showed a significantly higher risk of non-HCC-related death (p=0.006). CONCLUSIONS: The prevalence of MAFLD HCC in Italy is rapidly increasing to cover the majority of patients with HCC. Despite a less favourable cancer stage at diagnosis, patients with MAFLD HCC have a lower risk of HCC-related death, suggesting reduced cancer aggressiveness.

Exploiting node metadata to predict interactions in bipartite networks using graph embedding and neural networks.

Networks are increasingly used in various fields to represent systems with the aim of understanding the underlying rules governing observed interactions, and hence predict how the system is likely to behave in the future. Recent developments in network science highlight that accounting for node metadata improves both our understanding of how nodes interact with one another, and the accuracy of link prediction. However, to predict interactions in a network within existing statistical and machine learning frameworks, we need to learn objects that rapidly grow in dimension with the number of nodes. Thus, the task becomes computationally and conceptually challenging for networks. Here, we present a new predictive procedure combining a statistical, low-rank graph embedding method with machine learning techniques which reduces substantially the complexity of the learning task and allows us to efficiently predict interactions from node metadata in bipartite networks. To illustrate its application on real-world data, we apply it to a large dataset of tourist visits across a country. We found that our procedure accurately reconstructs existing interactions and predicts new interactions in the network. Overall, both from a network science and data science perspective, our work offers a flexible and generalizable procedure for link prediction.

Angiosarcoma and Vascular Surgery: A Case Report and Review of Literature.

INTRODUCTION: Angiosarcomas (AS) are rare and aggressive neoplasms originating from the endothelium: they represent less than 2% of all soft tissue sarcomas and usually have a poor prognosis. Although more often primary, different risk factors have been described and some cases are associated with vascular surgery. Materials and Methods: We present the case of an 84-year-old man who developed an AS on his thigh 3 years after a popliteal bypass with autologous saphenous vein. We performed a thorough review of the literature describing the main characteristics of the 25 cases (including ours) of AS associated with vascular surgery reported from 1981 to 2022. Results: Most of the patients were males (21 men vs 4 women) with a range age of 50-84 years. Most of AS are associated with Dacron grafts (12 cases), the overall mean time to onset is 7.8 years after surgery. The most common presenting symptoms are pain (20 cases) and weight loss (10 cases), while cutaneous presentation is uncommon; indeed, violaceous and painful papules, plaques, nodules, and skin ulceration have been found in 3 cases only. Due to unspecific symptoms, differential diagnosis is often difficult and a biopsy for histological confirmation is mandatory. Conclusion: Even if it seems to be a very rare complication, AS should always be considered in patients with compatible symptoms and who have undergone vascular surgery in the past.

Niche Packing and Local Coexistence in a Megadiverse Guild of Frugivorous Birds Are Mediated by Fruit Dependence and Shifts in Interaction Frequencies.

AbstractNiche packing is one of the prevailing mechanisms underlying the increase in the number of co-occurring species and the extraordinary diversity of tropical ecosystems. However, it is not yet understood whether niche packing is facilitated by higher specialization and reduced niche overlap or, rather, by diffuse competition and increased niche overlap. We combined highly resolved bird-plant interaction networks, bird phylogenies, and plant functional traits to compare dietary niche overlap and foraging frequencies among frugivorous birds at seven sites in the tropical Andes. We quantified niche overlap on the basis of the traits of the plants used by each bird and related it to the degree of niche packing at the different sites. Niche complementarity decreased with increasing niche packing, suggesting that increasingly dense niche packing is facilitated by increased niche overlap. Pairwise niche overlap was mediated by shifts in foraging frequencies away from shared resources, and it decreased with decreasing phylogenetic relatedness and increasing dependence on fruit as resource. Our findings suggest that foraging choices are a key axis of diversification in frugivorous birds and that differences in resource use frequencies are already sufficient to reduce potential competition between ecologically similar species and facilitate niche packing, especially if species differ in their dependence on particular resources.

COVID-19 infodemic on Facebook and containment measures in Italy, United Kingdom and New Zealand.

The COVID-19 pandemic has been characterized by a social media "infodemic": an overabundance of information whose authenticity may not always be guaranteed. With the potential to lead individuals to harmful decisions for the society, this infodemic represents a severe threat to information security, public health and democracy. In this paper, we assess the interplay between the infodemic and specific aspects of the pandemic, such as the number of cases, the strictness of containment measures, and the news media coverage. We perform a comparative study on three countries that employed different managements of the COVID-19 pandemic in 2020-namely Italy, the United Kingdom, and New Zealand. We first analyze the three countries from an epidemiological perspective to characterize the impact of the pandemic and the strictness of the restrictions adopted. Then, we collect a total of 6 million posts from Facebook to describe user news consumption behaviors with respect to the reliability of such posts. Finally, we quantify the relationship between the number of posts published in each of the three countries and the number of confirmed cases, the strictness of the restrictions adopted, and the online news media coverage about the pandemic. Our results show that posts referring to reliable sources are consistently predominant in the news circulation, and that users engage more with reliable posts rather than with posts referring to questionable sources. Furthermore, our modelling results suggest that factors related to the epidemiological and informational ecosystems can serve as proxies to assess the evolution of the infodemic.

Modification of MRI pattern of high-grade glioma pseudoprogression in regorafenib therapy.

Pseudoprogression (PP) is a diagnostic dilemma in the follow-up of brain high grade gliomas (HGG), and the introduction of new therapies has further complicated its identification in Magnetic Resonance Imaging (MRI). We report a case of pseudoprogression after intraoperative radiotherapy (ioRT) and Regorafenib therapy in a patient with anaplastic astrocytoma recurrence. A 65-year-old man, treated in August 2017 for a right frontal anaplastic astrocytoma, with surgical resection and following radiotherapy and Temozolomide, in October 2019 was again treated for peri-surgical bed recurrence with resection and ioRT followed by Regorafenib therapy, interrupted in February 2020, after the onset of adverse reactions. MRI examination showed a large irregular alteration posterior to the surgical bed, T2 weighted hypointense featuring strong diffusion restriction (low ADC values), with an irregular contrast-enhancement (CE) pattern, and surrounded by a vast vasogenic oedema; Dynamic Susceptibility Contrast (DSC) perfusion imaging (PWI) showed no increase of relative cerebral blood volume (rCBV). Particularly, lesion appeared markedly hypointense and dusty-like on susceptibility weighted images (SWI) probably due to a constant hemorrhagic diapedesis promoted by Regorafenib. Therefore, pseudoprogression was suspected. Follow-up MRI exams showed gradual reduction of SWI and CE abnormalities, but a persistent DWI restriction. Unfortunately, the last MRI control showed a secondary cerebellar localisation of the disease. New therapies are changing MRI pattern in HGG imaging and this case underlines how a multimodality approach is increasingly necessary. In particular, when using anti-VEGF drugs, SWI can have a crucial role in identifying therapy-related haemorrhagic changes.

Genomic characterization of hepatoid tumors: context matters.

Hepatoid tumors (HT) are rare neoplasms morphologically resembling hepatocellular carcinoma, which arise in several organs other than the liver. A comprehensive molecular profile of this group of neoplasms is still lacking. Genomic characterization of 19 HTs from different organs (three colon HTs, four esophagogastric HTs, four biliary HTs, six genitourinary HTs, two lung HTs) was performed using a multigene next-generation sequencing panel. NGS unraveled a composite molecular profile of HT. Their genetic alterations were clearly clustered by tumor site: (i) colorectal HT displayed microsatellite instability, high tumor mutational burden, mutations in ARID1A/B genes and NCOA4-RET gene fusion (2/3 cases); (ii) gastric HT had TP53 mutations (2/4); (iii) biliary HT displayed loss of CDKN2A (3/4) and loss of chromosome 18 (2/4); (iv) genital HT showed gain of chromosome 12 (3/6); (v) lung HT had STK11 somatic mutations (2/2). The only commonly mutated gene occurring in HT of different sites was TP53 (8/19 cases: colon 2, esophagogastric 2, biliary 2, genital 1, lungs 1). This study shows that most genetic alterations of HT were clustered by site, indicating that context matters. The novel potential targets for HT precision oncology are also clustered based on the anatomic origin. This study shed light on the biology of these rare cancers and may have important consequences for treatment decisions and clinical trial selection for HT patients.

Solid Organ Transplantation During COVID-19 Pandemic: An International Web-based Survey on Resources' Allocation.

Solid organ transplants (SOTs) are life-saving interventions, recently challenged by coronavirus disease 2019 (COVID-19). SOTs require a multistep process, which can be affected by COVID-19 at several phases. METHODS: SOT-specialists, COVID-19-specialists, and medical ethicists designed an international survey according to CHERRIES guidelines. Personal opinions about continuing SOTs, safe managing of donors and recipients, as well as equity of resources' allocation were investigated. The survey was sent by e-mail. Multiple approaches were used (corresponding authors from Scopus, websites of scientific societies, COVID-19 webinars). After the descriptive analysis, univariate and multivariate ordinal regression analysis was performed. RESULTS: There were 1819 complete answers from 71 countries. The response rate was 49%. Data were stratified according to region, macrospecialty, and organ of interest. Answers were analyzed using univariate-multivariate ordinal regression analysis and thematic analysis. Overall, 20% of the responders thought SOTs should not stop (continue transplant without restriction); over 70% suggested SOTs should selectively stop, and almost 10% indicated they should completely stop. Furthermore, 82% agreed to shift resources from transplant to COVID-19 temporarily. Briefly, main reason for not stopping was that if the transplant will not proceed, the organ will be wasted. Focusing on SOT from living donors, 61% stated that activity should be restricted only to "urgent" cases. At the multivariate analysis, factors identified in favor of continuing transplant were Italy, ethicist, partially disagreeing on the equity question, a high number of COVID-19-related deaths on the day of the answer, a high IHDI country. Factors predicting to stop SOTs were Europe except-Italy, public university hospital, and strongly agreeing on the equity question. CONCLUSIONS: In conclusion, the majority of responders suggested that transplant activity should be continued through the implementation of isolation measures and the adoption of the COVID-19-free pathways. Differences between professional categories are less strong than supposed.

Clinical relevant pancreatic fistula after pancreatoduodenectomy: when negative amylase levels tell the truth.

Drain Amylase level are routinely determined to diagnose pancreatic fistula after Pancreatocoduodenectomy. Consensus is lacking regarding the cut-off value of amylase to diagnosis clinically relevant postoperative pancreatic fistulae (POPF). The present study proposes a model based on Amylase Value in the Drain (AVD) measured in the first three postoperative days to predict a POPF. Amylase cut-offs were selected from a previous published systematic review and the accuracy were validated in a multicentre database from 12 centres in 2 countries. The present study defined POPF the 2016 ISGPS criteria (3 times the upper limit of normal serum amylase). A learning machine method was used to correlate AVD with the diagnosis of POPF. Overall, 454 (27%) of 1638 patients developed POPF. Machine learning excluded a clinically relevant postoperative pancreatic fistulae with an AUC of 0.962 (95% CI 0.940-0.984) in the first five postoperative days. An AVD at a cut-off of 270 U/L in 2 days in the first three postoperative days excluded a POPF with an AUC of 0.869 (CI 0.81-0.90, p < 0.0001). A single AVD in the first three postoperative days may not exclude POPF after pancreatoduodenectomy. The levels should be monitored until day 3 and have two negative values before removing the drain. In the group with a positive level, the drain should be kept in and AVD monitored until postoperative day five.

Related plants tend to share pollinators and herbivores, but strength of phylogenetic signal varies among plant families.

Related plants are often hypothesized to interact with similar sets of pollinators and herbivores, but this idea has only mixed empirical support. This may be because plant families vary in their tendency to share interaction partners. We quantify overlap of interaction partners for all pairs of plants in 59 pollination and 11 herbivory networks based on the numbers of shared and unshared interaction partners (thereby capturing both proportional and absolute overlap). We test for relationships between phylogenetic distance and partner overlap within each network; whether these relationships varied with the composition of the plant community; and whether well-represented plant families showed different relationships. Across all networks, more closely related plants tended to have greater overlap. The strength of this relationship within a network was unrelated to the composition of the network's plant component, but, when considered separately, different plant families showed different relationships between phylogenetic distance and overlap of interaction partners. The variety of relationships between phylogenetic distance and partner overlap in different plant families probably reflects a comparable variety of ecological and evolutionary processes. Considering factors affecting particular species-rich groups within a community could be the key to understanding the distribution of interactions at the network level.

Unmasking structural patterns in incidence matrices: an application to ecological data.

Null models have become a crucial tool for understanding structure within incidence matrices across multiple biological contexts. For example, they have been widely used for the study of ecological and biogeographic questions, testing hypotheses regarding patterns of community assembly, species co-occurrence and biodiversity. However, to our knowledge we remain without a general and flexible approach to study the mechanisms explaining such structures. Here, we provide a method for generating 'correlation-informed' null models, which combine the classic concept of null models and tools from community ecology, like joint statistical modelling. Generally, this model allows us to assess whether the information encoded within any given correlation matrix is predictive for explaining structural patterns observed within an incidence matrix. To demonstrate its utility, we apply our approach to two different case studies that represent examples of common scenarios encountered in community ecology. First, we use a phylogenetically informed null model to detect a strong evolutionary fingerprint within empirically observed food webs, reflecting key differences in the impact of shared evolutionary history when shaping the interactions of predators or prey. Second, we use multiple informed null models to identify which factors determine structural patterns of species assemblages, focusing in on the study of nestedness and the influence of site size, isolation, species range and species richness. In addition to offering a versatile way to study the mechanisms shaping the structure of any incidence matrix, including those describing ecological communities, our approach can also be adapted further to test even more sophisticated hypotheses.

Author Correction: Prioritizing phylogenetic diversity captures functional diversity unreliably.

The original version of this Article contained a plotting error in Fig. 3g. The Serranidae and Siganidae families were misplaced in the plotted phylogeny. This error has now been corrected in the PDF and HTML versions of the Article. For comparison, the original, incorrect version of Fig. 3g is presented below as Fig. 1. The authors thank P. Cowman for identifying the plotting error.

Tracheobronchopathia Osteochondroplastica: A Case Report Illustrating the Importance of Multilevel Workup Clinical, Endoscopic and Histological Assessment in Diagnosis of an Uncommon Disease.

BACKGROUND Tracheobronchopathia osteochondroplastica (TO) is a rare idiopathic disease with a stable course, which involves the lumen of the tracheobronchial tree. Clinical manifestations at time of presentation may differ, typically including hoarseness, persistent and/or productive cough, hemoptyses, and dyspnea. There are no well-established guidelines for diagnostic workup and treatment. Our aim here is to present a paradigmatic case of TO together with a concise survey of the most important clinical, radiological, and histological criteria. CASE REPORT We report a case of a 62-year-old non-smoker male with persisting cough and no prior history of respiratory disease. Chest radiography (RX) and computed tomography (CT) were unremarkable. Given the persistence of symptoms, the patient underwent bronchoscopic examination, which revealed protruding sessile nodules into the tracheal lumen, with cobblestone appearance. Histopathological examination of biopsies taken during bronchoscopy showed cartilaginous and osseous submucosal nodules consistent with the diagnosis of TO. CONCLUSIONS TO is not always an easily recognized disease, and a multidisciplinary team work is often required for diagnosis, with particular importance of endoscopic-pathological correlation.

Analysing ecological networks of species interactions.

Network approaches to ecological questions have been increasingly used, particularly in recent decades. The abstraction of ecological systems - such as communities - through networks of interactions between their components indeed provides a way to summarize this information with single objects. The methodological framework derived from graph theory also provides numerous approaches and measures to analyze these objects and can offer new perspectives on established ecological theories as well as tools to address new challenges. However, prior to using these methods to test ecological hypotheses, it is necessary that we understand, adapt, and use them in ways that both allow us to deliver their full potential and account for their limitations. Here, we attempt to increase the accessibility of network approaches by providing a review of the tools that have been developed so far, with - what we believe to be - their appropriate uses and potential limitations. This is not an exhaustive review of all methods and metrics, but rather, an overview of tools that are robust, informative, and ecologically sound. After providing a brief presentation of species interaction networks and how to build them in order to summarize ecological information of different types, we then classify methods and metrics by the types of ecological questions that they can be used to answer from global to local scales, including methods for hypothesis testing and future perspectives. Specifically, we show how the organization of species interactions in a community yields different network structures (e.g., more or less dense, modular or nested), how different measures can be used to describe and quantify these emerging structures, and how to compare communities based on these differences in structures. Within networks, we illustrate metrics that can be used to describe and compare the functional and dynamic roles of species based on their position in the network and the organization of their interactions as well as associated new methods to test the significance of these results. Lastly, we describe potential fruitful avenues for new methodological developments to address novel ecological questions.