Search

The most common somatic alteration in primary prostate cancer is the TMPRSS2:ERG gene fusion, which may be caused or promoted by distinct etiologic factors. The objective of this systematic review was to assess epidemiologic evidence on etiologic factors for prostate cancer by tumor TMPRSS2:ERG fusion status in human populations. Of 3071 publications identified, 19 cohort or case-control studies from six distinct study populations were included in this systematic review. Etiologic factors included germline genetic variants, circulating hormones, and dietary and lifestyle factors. Taller height, higher total and free testosterone levels, and fewer trinucleotide repeats in AR were possibly associated with higher risk of TMPRSS2:ERG-positive prostate cancer. Excess body weight, greater vigorous physical activity, higher lycopene intake, and the use of calcium channel blockers were associated with lower risk of TMPRSS2:ERG-positive prostate cancer. Diabetes and family history of prostate cancer were associated with both TMPRSS2:ERG-positive and TMPRSS2:ERG-negative prostate cancer. Prostate cancer germline variants had suggestive differential associations with TMPRSS2:ERG-positive or TMPRSS2:ERG-negative prostate cancer. However, results were based on few distinct study populations and generally had low precision, underscoring the need for replication. In conclusion, prostate cancer with TMPRSS2:ERG fusion is an etiologically distinct subtype that may be, in part, preventable by addressing modifiable and hormonally acting etiologic factors that align with the established mechanistic role of TMPRSS2:ERG in androgen, insulin, antioxidant, and growth factor pathways., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Pneumoperitoneum, which is established for laparoscopic surgery, has systemic implications on the renal system and may contribute to acute kidney injury or postoperative renal dysfunction. Specifically, when the pressure exceeds 10 mmHg, pneumoperitoneum decreases renal blood flow, leading to renal dysfunction and temporary oliguria. The renal effects of pneumoperitoneum stem from both the direct effects of increased intra-abdominal pressure and indirect factors such as carbon dioxide absorption, neuroendocrine influences, and tissue damage resulting from oxidative stress. While pneumoperitoneum can exacerbate renal dysfunction in patients with pre-existing kidney issues, preserving the function of the remaining kidney is crucial in certain procedures such as laparoscopic live donor nephrectomy. However, available evidence on the effects of pneumoperitoneum on renal function is limited and of moderate quality. This review focuses on exploring the pathophysiological hypotheses underlying kidney damage, mechanisms leading to oliguria and kidney damage, and fluid management strategies for surgical patients during pneumoperitoneum.

Due to the recent pandemic, new teaching methods have been trialed, even in traditional disciplines such as histopathology, which typically involve extensive hands-on laboratory work. In this study, we investigated the effects of three different learning modalities in histopathology teaching: optical microscopy, in-class virtual microscopy (VM), and online VM lectures. We examined relational aspects, didactic effectiveness, and satisfaction of these learning settings, both during class time and in private study, outside the dedicated spaces and hours of the university. The comparative design of the study, based on a set of surveys taken during the course and at its end, resulted in valuable methodological insights and a clear picture of the students' needs. These were characterized both by high technological expectations and by desire for a stimulating social environment. Our results show that the implementation of new learning tools has a positive impact on teaching, and not only at the didactic level. It also positively affects the way the university is experienced by the students, it facilitates their wanted socializing lifestyles, and it exposes them, as a new generation of professionals, to the latest technologies used by specialty physicians.

TOTTA outlines the spatial position and rotation guidance of a real/virtual tool (TO) towards a real/virtual target (TA), which is a key task in Mixed reality applications. The task error can have critical consequences regarding safety, performance, and quality, such as surgical implantology or industrial maintenance scenarios. The TOTTA problem lacks a dedicated study and it is scattered in different domains with isolated designs. This work contributes to a systematic review of the TOTTA visual widgets, studying 70 unique designs from 24 papers. TOTTA is commonly guided by the visual overlap -an intuitive, pre-attentive "collimation" feedback- of simple shaped widgets: Box, 3D Axes, 3D Model, 2D Crosshair, Globe, Tetrahedron, Line, Plane. Our research discovers that TO and TA are often represented with the same shape. They are distinguished by topological elements (e.g. edges/vertices/faces), colors, transparency levels, and added. shapes, widget quantity, and size. Meanwhile some designs provide continuous "during manipulation feedback" relative to the distance between TO and TA by text, dynamic color, sonification, and amplified graphical visualization. Some approaches trigger discrete "TA reached feedback" such as color alteration, added sound, TA shape change, and added text. We found the lack of golden standards, including in testing procedures, as current ones are limited to partial sets with different and incomparable setups (different target configurations, avatar, background, etc.). We also found a bias in participants: right-handed, young male, non-color impaired.

Mixed Reality (MR) is proven in the literature to support precise spatial dental drill positioning by superimposing 3D widgets. Despite this, the related knowledge about widget's visual design and interactive user feedback is still limited. Therefore, this study is contributed to by co-designed MR drill tool positioning widgets with two expert dentists and three MR experts. The results of co-design are two static widgets (SWs): a simple entry point, a target axis, and two dynamic widgets (DWs), variants of dynamic error visualization with and without a target axis (DWTA and DWEP). We evaluated the co-designed widgets in a virtual reality simulation supported by a realistic setup with a tracked phantom patient, a virtual magnifying loupe, and a dentist's foot pedal. The user study involved 35 dentists with various backgrounds and years of experience. The findings demonstrated significant results; DWs outperform SWs in positional and rotational precision, especially with younger generations and subjects with gaming experiences. The user preference remains for DWs (19) instead of SWs (16). However, findings indicated that the precision positively correlates with the time trade-off. The post-experience questionnaire (NASA-TLX) showed that DWs increase mental and physical demand, effort, and frustration more than SWs. Comparisons between DWEP and DWTA show that the DW's complexity level influences time, physical and mental demands. The DWs are extensible to diverse medical and industrial scenarios that demand precision.

Recently, volatile organic compound (VOC) determination in exhaled breath has seen growing interest due to its promising potential in early diagnosis of several pathological conditions, including chronic kidney disease (CKD). Therefore, this study aimed to identify the breath VOC pattern providing an accurate, reproducible and fast CKD diagnosis at early stages of disease. A cross-sectional observational study was carried out, enrolling a total of 30 subjects matched for age and gender. More specifically, the breath samples were collected from (a) 10 patients with end-stage kidney disease (ESKD) before undergoing hemodialysis treatment (DIAL); (b) 10 patients with mild-moderate CKD (G) including 3 patients in stage G2 with mild albuminuria, and 7 patients in stage G3 and (c) 10 healthy controls (CTRL). For each volunteer, an end-tidal exhaled breath sample and an ambient air sample (AA) were collected at the same time on two sorbent tubes by an automated sampling system and analyzed by Thermal Desorption-Gas Chromatography-Mass Spectrometry. A total of 110 VOCs were detected in breath samples but only 42 showed significatively different levels with respect to AA. Nonparametric tests, such as Wilcoxon/Kruskal-Wallis tests, allowed us to identify the most weighting variables able to discriminate between AA, DIAL, G and CTRL breath samples. A promising multivariate data mining approach incorporating only selected variables (showing p -values lower than 0.05), such as nonanal, pentane, acetophenone, pentanone, undecane, butanedione, ethyl hexanol and benzene, was developed and cross-validated, providing a prediction accuracy equal to 87% and 100% in identifying patients with both mild-moderate CKD (G) and ESKD (DIAL), respectively.

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Thoracic epidural catheters (TECs) are useful adjuncts to multimodal pain regimens in traumatic rib fractures. However, TEC placement is limited by contraindications, patient risk profile, and provider availability. Continuous peripheral infusion of ketamine and/or lidocaine is an alternative that has a modest risk profile and few contraindications. We hypothesized that patients with multiple traumatic rib fractures receiving TECs would have better pain control, in terms of daily morphine milligram equivalents (MMEs) and mean pain scores (MPSs) when compared with continuous peripheral infusions of ketamine and/or lidocaine., Methods: We retrospectively analyzed traumatic rib fracture admissions to a level 1 trauma center between January 2018 and December 2020. We evaluated two treatment groups: TEC only and continuous infusion only (drip only). A linear mixed-effects model evaluated the association of MME with treatment group. An interaction term of treatment group by time (days 1-7) was included to allow estimating potential time-dependent treatment effect on MME. A zero-inflated Poisson mixed-effects model evaluated the association of treatment with MPS. Both models adjusted for confounders., Results: A total of 1,647 patients were included. After multivariable analysis, a significant, time-varying dose-response relationship between treatment group and MME was found, indicating an opioid-sparing effect favoring the TEC-only group. The opioid-sparing benefit for TEC-only therapy was most prominent at day 3 (27.4 vs 36.5 MME) and day 4 (27.3 vs 36.2 MME) (p < 0.01). The drip-only group had 1.21 times greater MPS than patients with TEC only (p < 0.001)., Conclusion: Drip-only analgesia is associated with higher daily MME use and MPS, compared with TEC only. The maximal benefit of TEC therapy appears to be on days 3 and 4. Prospective, randomized comparison between groups is necessary to evaluate the magnitude of the treatment effect., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Embryonic-type neuroectodermal tumor (ENT) is a somatic-type malignancy characterized by overgrowth of embryonic-type neuroectodermal tissue (EtNT). In germ cell tumors, EtNT is frequently intermingled with other components that may exhibit significant morphologic overlap [mature neuro-glial tissue (MNGT), nephroblastomatous tissues, and primitive endodermal-type glands]. Therefore, the quantification of EtNT (crucial for the diagnosis of ENT) can be challenging. In this study, we investigated the immunohistochemical profile of ENT, EtNT, and MNGT using a broad immunohistochemical panel. We found that SOX2 was the most sensitive marker for EtNT (100%), but it also stained MNGT (28.6%). GFAP and S100 were relatively sensitive (71.4%) and highly specific (GFAP 100%, S100 85.8%) for MNGT, whereas synaptophysin stained both. Combining our results with those of previous studies, we propose that a combination of SOX11, SOX2, GFAP, S100, AFP, villin, CDX2, PAX8, and nuclear WT1 may help to identify and quantify EtNT in germ cell tumors., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sepsis, the dysregulated immune response of the host to infections, leads to numerous complications, including multiple organ dysfunction with sepsis-associated acute kidney injury (SA-AKI) being a frequent complication associated with increased risk of mortality and the progression toward chronic kidney disease (CKD). Several mechanisms have been widely investigated in understanding the complex pathophysiology of SA-AKI, including hemodynamic alterations, inflammation, oxidative stress, and direct cellular injury driven by pathogens or cell-derived products (pathogen-associated molecular patterns and damage-associated molecular patterns). Despite advancements in the management of septic patients, the prognosis of SA-AKI patients remains significantly poor and is associated with high in-hospital mortality and adverse long-term outcomes. Therefore, recent research has focused on the early identification of specific SA-AKI endotypes and subphenotypes through epigenetic analysis and the use of potential biomarkers, either alone or in combination with clinical data, to improve prognosis. Epigenetic regulation, such as DNA methylation, histone modifications, and noncoding RNA modulation, is crucial in modulating gene expression in response to stress and renal injury in SA-AKI. At the same time, these modifications are dynamic and reversible processes that can alter gene expression in several pathways implicated in the context of SA-AKI, including inflammation, immune response, and tolerance status. In addition, specific epigenetic modifications may exacerbate renal damage by causing persistent inflammation or cellular metabolic reprogramming, leading to progression toward CKD. This review aims to provide a comprehensive understanding of the epigenetic characteristics that define SA-AKI, also exploring targeted therapies that can improve patient outcomes and limit the chronic progression of this syndrome., Competing Interests: S.D.R. received honoraria from Estor, Toray, Biotest, Baxter, Fresenius Medical. M.F. received speaker fees from Estor, Biomereux, Astrazeneca. V.C. received speaker fees from Estor, Toray, Jafron, Baxter, Cytosorbents, Aferetica, Mozarc Medical, Astrazeneca., (Thieme. All rights reserved.)

Background: Acute kidney injury (AKI) during hospitalization is associated with increased complications and mortality. Despite efforts to standardize AKI management, its recognition in clinical practice is limited., Methods: To assess and characterize different patterns of AKI diagnosis, we collected clinical data, serum creatinine (sCr) levels, comorbidities and outcomes from adult patients using the Hospital Discharge Form (HDF). AKI diagnosis was based on administrative data and according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria by evaluating sCr variations during hospitalization. Additionally, patients were categorized based on the timing of AKI onset., Results: Among 56 820 patients, 42 900 (75.5%) had no AKI, 1893 (3.3%) had AKI diagnosed by sCr changes and coded in the HDF (full-AKI), 2529 (4.4%) had AKI reported on the HDF but not meeting sCr-based criteria (HDF-AKI) and 9498 (16.7%) had undetected AKI diagnosed by sCr changes but not coded in the HDF (KDIGO-AKI). Overall, AKI incidence was 24.5%, with a 68% undetection rate. Patients with KDIGO-AKI were younger and had a higher proportion of females, lower comorbidity burden, milder AKI stages, more frequent admissions to surgical wards and lower mortality compared with full-AKI patients. All AKI groups had worse outcomes than those without AKI, and AKI, even if undetected, was independently associated with mortality risk. Patients with AKI at admission had different profiles and better outcomes than those developing AKI later., Conclusions: AKI recognition in hospitalized patients is highly heterogeneous, with a significant prevalence of undetection. This variability may be affected by patients' characteristics, AKI-related factors, diagnostic approaches and in-hospital patient management. AKI remains a major risk factor, emphasizing the importance of ensuring proper diagnosis for all patients., Competing Interests: The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: The recruitment-to-inflation ratio (R/I) has been recently proposed to bedside assess response to PEEP. The impact of PEEP on ventilator-induced lung injury depends on the extent of dynamic strain reduction. We hypothesized that R/I may reflect the potential for lung recruitment (i.e. recruitability) and, consequently, estimate the impact of PEEP on dynamic lung strain, both assessed through computed tomography scan., Methods: Fourteen lung-damaged pigs (lipopolysaccharide infusion) underwent ventilation at low (5 cmH 2 O) and high PEEP (i.e., PEEP generating a plateau pressure of 28-30 cmH 2 O). R/I was measured through a one-breath derecruitment maneuver from high to low PEEP. PEEP-induced changes in dynamic lung strain, difference in nonaerated lung tissue weight (tissue recruitment) and amount of gas entering previously nonaerated lung units (gas recruitment) were assessed through computed tomography scan. Tissue and gas recruitment were normalized to the weight and gas volume of previously ventilated lung areas at low PEEP (normalized-tissue recruitment and normalized-gas recruitment, respectively)., Results: Between high (median [interquartile range] 20 cmH 2 O [18-21]) and low PEEP, median R/I was 1.08 [0.88-1.82], indicating high lung recruitability. Compared to low PEEP, tissue and gas recruitment at high PEEP were 246 g [182-288] and 385 ml [318-668], respectively. R/I was linearly related to normalized-gas recruitment (r = 0.90; [95% CI 0.71 to 0.97) and normalized-tissue recruitment (r = 0.69; [95% CI 0.25 to 0.89]). Dynamic lung strain was 0.37 [0.29-0.44] at high PEEP and 0.59 [0.46-0.80] at low PEEP (p < 0.001). R/I was significantly related to PEEP-induced reduction in dynamic (r = - 0.93; [95% CI - 0.78 to - 0.98]) and global lung strain (r = - 0.57; [95% CI - 0.05 to - 0.84]). No correlation was found between R/I and and PEEP-induced changes in static lung strain (r = 0.34; [95% CI - 0.23 to 0.74])., Conclusions: In a highly recruitable ARDS model, R/I reflects the potential for lung recruitment and well estimates the extent of PEEP-induced reduction in dynamic lung strain., (© 2024. The Author(s).)

Background: Testicular Leydig cell tumours (LCTs) are the most common type of sex cord-stromal tumour in men, representing 1%-3% of all testicular neoplasms. Among testicular sex cord-stromal tumours, CTNNB1 mutations and nuclear expression of β-catenin have been typically associated with Sertoli cell tumour. Recent genomic analyses have shown that CTNNB1 variants are also identified in a subset of LCTs; however, the frequency and clinicopathologic associations of β-catenin alterations remain incompletely understood in this tumour type., Methods: In this study, we evaluated 32 LCTs (five malignant/metastasizing, 27 nonmetastasizing) using β-catenin immunohistochemistry and DNA sequencing., Results: Immunohistochemistry revealed focal or multifocal nuclear β-catenin expression in 47% of the tumours. Diffuse nuclear β-catenin expression (in >50% of the tumour cells) was not detected in any of the cases analysed herein. Comparison of β-catenin-positive and β-catenin-negative cases did not show significant differences in the frequency of adverse histopathologic findings or malignant clinical behaviour. DNA sequencing performed de novo on a subset of seven cases revealed the presence of exon 3 CTNNB1 variants in four of them (4/7, 57%), with variant allele frequencies (VAF) ranging from 7 to 33%. Two additional β-catenin-positive cases that had been sequenced as part of a previous study harboured exon 3 CTNNB1 variants at VAF of 28% and 7%, respectively., Conclusion: These results demonstrate that β-catenin alterations are relatively common in LCT, most likely occurring as subclonal events that are not enriched in cases with aggressive features. Further studies are needed to clarify the oncogenic role of β-catenin in this tumour type., (© 2024 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Postchemotherapy postpubertal-type yolk sac tumors (YST) with glandular and solid phenotypes are aggressive and commonly resistant to systemic chemotherapy. These neoplasms show morphologic features that significantly overlap with those of somatic carcinomas with "enteroblastic" or "fetal" phenotype (the preferred terminology depends on the site of origin). They often present as late or very late recurrences, and their diagnosis is challenging because they frequently affect patients in an age group at risk for carcinomas of somatic origin. Recently, we incidentally identified examples of postchemotherapy glandular and solid YST with "enteroblastic" phenotypes and nuclear expression of beta-catenin, prompting us to further evaluate the prevalence of this phenomenon. We found nuclear expression of beta-catenin in 10 (29%) of 34 such tumors. A subset of cases with nuclear beta-catenin expression was further analyzed with a DNA sequencing panel (n = 6) and fluorescence in situ hybridization for isochromosome 12p [i(12p); n = 5]. Sequencing identified exon 3 CTNNB1 variants in 3 (50%) of 6 analyzed cases, and fluorescence in situ hybridization was positive for i(12p) in 5 of 5 cases. In conclusion, a significant subset of postchemotherapy YST with glandular or solid architecture and "enteroblastic" phenotype demonstrates beta-catenin alterations, suggesting that activation of Wnt signaling may play a role in the progression of these neoplasms. Moreover, nuclear beta-catenin expression in these tumors represents a potential diagnostic pitfall given that carcinomas of true somatic origin with overlapping morphology may also be positive for this marker., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

The HIV epidemics in Cambodia is concentrated in key populations (KPs). Pre-exposure prophylaxis (PrEP) has been officially approved in the country since 2019. However, its use may still be controversial after a PrEP clinical trial was interrupted in Cambodia after being deemed unethical in 2004. In this context, it was necessary to evaluate PrEP acceptability and administration preferences of KPs in Cambodia, with a view to increasing roll-out and uptake. We conducted a qualitative study in 2022 comprising six focus groups and four semi-structured individual interviews with transgender women, men who have sex with men, male entertainment workers, venue-based female entertainment workers (FEW), street-based FEW, and PrEP users who participated in a PrEP pilot study that started in 2019. Overall, KPs positively perceived PrEP, with some reservations. They preferred daily, community-based PrEP to event-driven, hospital-based PrEP, and highlighted that injectable PrEP would be a potential option if it became available in Cambodia. We recommend (i) proposing different PrEP regimens and PrEP delivery-models to broaden PrEP acceptability and adherence in Cambodia (ii) increasing the number of community-based organisations and improving the services they offer, (iii) rolling out injectable PrEP when it becomes officially available, and (iv) improving PrEP side effects information.

The metaverse, driven by mixed reality (MR), is positioned as the future market, revolutionizing product exploration in virtual space. Existing literature on this subject mainly focuses on business-to-consumer perspectives, leaving a gap in understanding business-to-business (B2B) applications, particularly in the fashion industry. This article introduces a "Mixed Tangible Catalog" (MTC) for B2B that combines a physical, foldable cardboard booth with an MR application linked to a head-mounted display. Targeting the fashion sector's need for high standards in material evaluation, the MTC allows retailers and distributors to browse garments, customize material attributes, and receive visual and tangible feedback. Evaluation through a focus group of 10 industry experts revealed positive feedback. The MTC maintains the tangibility of traditional B2B showrooms and reduces the environmental impact by minimizing transportation, samples, and waste. This innovative approach offers an efficient and sustainable alternative to conventional physical showrooms, enhancing both economic and ecological aspects.

Distorted body representations play a major role in the onset and maintenance of Schizophrenia. However, these distortions are difficult to assess because explicit assessments can provoke intense fears about the body and require a good insight. We proposed an implicit motor imagery task to a 14-year-old girl with Early-Onset Schizophrenia. The test consisted of presenting different openings varying in width. For each aperture, the young girl has to say if she could pass through without turning her shoulders. A critical aperture is determined as the first aperture for which she considered she could no longer pass, compared to her shoulders' width. The girl perceived herself as 51 % wider than she was, indicating a significant oversized body schema. The implicit assessments of body schema generate less anxiety and does not require a great level of insight; moreover, those are promising tools for early detection of disease in prodromal phases of Schizophrenia and assistance with differential diagnosis., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Published by Elsevier Inc.)

Background: The benefits of mitral repair versus replacement for endocarditis are inconclusive. This study compares outcomes of patients with infective endocarditis undergoing mitral valve repair versus replacement and investigates the impact of microbial etiology., Methods: All 251 patients undergoing mitral valve surgery for active endocarditis between 2010 and 2023 were enrolled, 180 (71.7%) replacement and 71 (28.3%) repair. To adjust for imbalances, inverse probability of treatment weighting was applied and 187 patients were obtained., Results: The analysis between groups, following the application of inverse probability of treatment weighting, showed no statistically significant differences across all considered outcomes. Early and late death was observed respectively in 6 (8.5%) and 11 (15.5%) patients in the repair group versus 24 (13.3%) and 45 (25.0%) in the replacement group without statistical significance ( p = 0.221 and p = 0.446). Relapse occurred in six patients (8.5%) in the repair group after a median time of 4.0 months and in six (3.3%) in the replacement after 6.9 months ( p = 0.071)., Conclusions: Surgical strategy in mitral endocarditis has no effect on major postoperative complications, mortality, or medium/long-term survival. Staphylococcus aureus and Coagulase-negative Staphylococci represent a risk for early mortality and relapse. However, mitral valve repair for endocarditis can be pursued when it ensures the complete eradication of all infected tissue, particularly in cases caused by Streptococcus infection, in young patients, and after a minimum of 18 days of antibiotic therapy.

Faecal microbiota plays a critical role in human health, but its relationship with nutritional status among schoolchildren remains under-explored. Here, in a double-blinded cluster-randomized controlled trial on 380 Cambodian schoolchildren, we characterize the impact of six months consumption of two types of rice fortified with different levels of vitamins and minerals on pre-specified outcomes. We investigate the association between the faecal microbiota (16SrRNA sequencing) and age, sex, nutritional status (underweight, stunting), micronutrient status (iron, zinc and vitamin A deficiencies, anaemia, iron deficient anaemia, hemoglobinopathy), inflammation (systemic, gut), and parasitic infection. We show that the faecal microbiota is characterised by a surprisingly high proportion of Lactobacillaceae. We discover that deficiencies in specific micronutrients, such as iron and vitamin A, correlate with particular microbiota profiles, whereas zinc deficiency shows no such association. The nutritional intervention with the two rice treatments impacts both the composition and functions predicted from compositional analysis in different ways. (ClinicalTrials.gov (Identifier: NCT01706419))., (© 2024. The Author(s).)

Background: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD., Methods: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease., Findings: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms., Interpretation: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

In the post-chemotherapy setting, germ cell tumors of the testis (GCTT) that resemble non-specific sarcomas and co-express cytokeratins and glypican-3 (GPC3) are diagnosed as "sarcomatoid yolk sac tumor postpubertal-type (YSTpt)". The diagnosis of sarcomatoid YSTpt is clinically relevant but challenging due to its rarity, non-specific histology, and negative α-fetoprotein (AFP) staining. Recently, FOXA2 has emerged as a key-gene in the reprogramming of GCTT (activating the transcription of several genes, among which GATA3), and immunohistochemical studies showed that GATA3 and FOXA2 have a higher sensitivity for non-sarcomatoid YSTpt than GPC3 and AFP. We found that sarcomatoid YSTpt did not express FOXA2 [0: 14/14 (100%)] and showed focal expression of GATA3 [0: 12/14 (85.7%), 1 + : 2/14 (14.3%)], thus suggesting that these markers are not useful in diagnosing this tumor. Furthermore, we proposed a potential mechanism of sarcomatoid transformation in the post-chemotherapy setting of GCTT, mediated by the downregulation of FOXA2 and GATA3., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Myocarditis is a polymorphic and potentially life-threatening disease characterized by a large variability in clinical presentation and prognosis. Within the broad spectrum of etiology, eosinophilic myocarditis represents a rare condition characterized by eosinophilic infiltration of the myocardium, usually associated with peripheral eosinophilia. Albeit uncommon, eosinophilic myocarditis could be potentially life-threatening, ranging from mild asymptomatic disease to multifocal widespread infiltrates associated with myocardial necrosis, thrombotic complications, and endomyocardial fibrosis. Moreover, it could progress to dilated cardiomyopathy, resulting in a poor prognosis. The leading causes of eosinophilic myocarditis are hypersensitivity reactions, eosinophilic granulomatosis with polyangiitis, cancer, hyper-eosinophilic syndrome variants, and infections. A thorough evaluation and accurate diagnosis are crucial to identifying the underlying cause and defining the appropriate therapeutic strategy. On these bases, this comprehensive review aims to summarize the current knowledge on eosinophilic myocarditis, providing a schematic and practical approach to diagnosing, evaluating, and treating eosinophilic myocarditis.

Chromotherapy rooms (CRs) are physical spaces with colored lights able to enhance an individual's mood, well-being, and, in the long term, their health. Virtual reality technology can be used to implement CR (VRCRs) and provide higher flexibility at lower costs. However, existing VRCRs are limited to a few use cases, and they do not fully explore the potential and pitfalls of the technology. This work contributes by comparing three VRCR designs: empty, static, and dynamic. Empty is just a void but a blue-colored environment. Static adds static abstract graphics (flowers and sea texture), and dynamic adds dynamic elements (animated star particle systems, fractals, and ocean flow). All conditions include relaxing low-beta and ocean sounds. We conducted a between-subject experiment ( n = 30) with the three conditions. Subjects compiled a self-perceived questionnaire and a mathematical stress test before and after the VRCR experience. The results demonstrated that the dynamic condition provided a higher sense of presence, while the self-perceived stress level was insignificant. Dynamic VR conditions are perceived as having a shorter duration, and participants declared that they felt more involved and engaged than in the other conditions. Overall, the study demonstrated that VRCRs have a non-trivial behavior and need further study of their design, especially considering their role in a future where VR will be an everyday working interface.

This article examines the choices between sitting and standing in virtual reality (VR) experiences, addressing conflicts, challenges, and opportunities. It explores issues such as the risk of motion sickness in stationary users and virtual rotations, the formation of mental models, consistent authoring, affordances, and the integration of embodied interfaces for enhanced interactions. Furthermore, it delves into the significance of multisensory integration and the impact of postural mismatches on immersion and acceptance in VR. Ultimately, the article underscores the importance of aligning postural choices and embodied interfaces with the goals of VR applications, be it for entertainment or simulation, to enhance user experiences.

Background: Septic shock, a critical condition characterized by organ failure, presents a substantial mortality risk in intensive care units (ICUs), with the 28-day mortality rate possibly reaching 40%. Conventional management of septic shock typically involves the administration of antibiotics, supportive care for organ dysfunction, and, if necessary, surgical intervention to address the source of infection. In recent decades, extracorporeal blood purification therapies (EBPT) have emerged as potential interventions aimed at modulating the inflammatory response and restoring homeostasis in patients with sepsis. Likewise, sequential extracorporeal therapy in sepsis (SETS) interventions offer comprehensive organ support in the setting of multiple organ dysfunction syndrome (MODS). The EROICASS study will assess and describe the utilization of EBPT in patients with septic shock. Additionally, we will evaluate the potential association between EBPT treatment utilization and 90-day mortality in septic shock cases in Italy., Methods: The EROICASS study is a national, non-interventional, multicenter observational prospective cohort study. All consecutive patients with septic shock at participating centers will be prospectively enrolled, with data collection extending from intensive care unit (ICU) admission to hospital discharge. Variables including patient demographics, clinical parameters, EBPT/SETS utilization, and outcomes will be recorded using a web-based data capture system. Statistical analyses will encompass descriptive statistics, hypothesis testing, multivariable regression models, and survival analysis to elucidate the associations between EBPT/SETS utilization and patient outcomes., Conclusions: The EROICASS study provides valuable insights into the utilization and outcomes of EBPT and SETS in septic shock management. Through analysis of usage patterns and clinical data, this study aims to guide treatment decisions and enhance patient care. The implications of these findings may impact clinical guidelines, potentially improving survival rates and patient outcomes in septic shock cases., (© 2024. The Author(s).)

Patients with chronic kidney disease (CKD), particularly those with end-stage renal disease (ESRD), have a high prevalence of cardiovascular disease and peripheral arterial disease (PAD). Medical treatment is mainly based on risk factor management, and the surgical approach remains the gold standard treatment in specific conditions. Heparin-mediated extracorporeal low-density lipoprotein precipitation (H.E.L.P.) apheresis is effective in reducing circulating lipoprotein, fibrinogen, inflammatory mediators and procoagulant factors, thereby reducing cardiovascular risk in patients with familial hypercholesterolemia and hypertriglyceridemia. These activities may be effective in reducing symptoms and ischemic vascular lesions even in patients with severe PAD. We reported the application of a treatment protocol with H.E.L.P. apheresis in an ESRD patient with severe PAD without clinical improvement after severe revascularization who was not suitable for further surgical approaches, despite normal LDL cholesterol and lipoprotein (a). The H.E.L.P. protocol was characterized by an intensive first phase with weekly treatments followed by a single session every 10-15 days for 6 months of treatment. The overall clinical condition, foot lesions and walking distance improved significantly after the first 2 months of treatment, and foot amputation was avoided. Here, we review the main pathogenetic mechanisms through which LDL apheresis improves microcirculation and clinical outcomes. Its wider application may represent an optimal therapeutic option for patients unresponsive to standard treatment.

Background: Identifying biomarkers for metastatic renal cell carcinoma (mRCC) is an unmet need in actual immunotherapy era. Available data regarding chromosome 3p genes (i.e., VHL, PBRM1, SETD2) mutations as potential predictors for therapy response is conflicting. We describe the impact of these mutations on clinical outcomes in mRCC patients treated with immune checkpoint inhibitor (ICI)-doublet or ICI/tyrosine kinase inhibitor (TKI) combinations., Methods: We performed a single-center retrospective analysis on mRCC patients treated with first line ICI/ICI or ICI/TKI. A multi-gene panel was used, allowing the amplification of 841 amplicons (54.93 kb, human reference sequence hg19/GRCh37) in the coding sequences of the following genes: ATM, BAP1, KDM5C, MET, MTOR, NF2, PBRM1, PIK3CA, PTEN, SETD2, SMARCB1, TP53, TSC1, TSC2, VHL., Results: 18 patients undergoing ICI/ICI and ICI/TKI who had tumor tissue adequate for molecular analysis were included. Histology was 100% clear cell. IMDC risk was 50% intermediate, 33.4% good, 16.6% poor. First line therapy was 89% ICI/TKI, 11% ICI/ICI. 83.3% pts (n = 15) carried genomic alterations (GA). Most common GA included VHL in 44% (n = 8; 7 pathogenic - PAT and 1 variant of unknown significance - VUS), PBRM1 in 44% (n = 8; 5 PAT and 3 VUS) and SETD2 in 33% (n = 6; 4 PAT and 2 VUS). With the limit of a small sample that did not allow proper statistical analyses, SETD2-mutated patients had lower median progression free (mPFS) and overall survival (mOS) than non-SETD2 mutated patients. Higher mPFS and mOS were shown with VHL or PBRM1 GA, especially in PBRM1 +VHL mutated pts., Conclusions: Our data shows a possible negative predictive role of SETD2 GA for ICI-based therapy in RCC. Concomitant VHL and PBRM1 GA could act as a predictor for ICI/TKI efficacy. Our hypothesis-generating analysis highlights the need of an integrated evaluation of these genes as promising biomarkers in RCC. Further larger studies are required., Competing Interests: Declaration of Competing Interest Francesco Massari has received research support and/or honoraria from Astellas, BMS, Janssen, Ipsen, MSD and Pfizer outside the submitted work.The other Authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Iatrogenic injuries to the circumflex coronary artery during mitral valve surgery are probably underestimated (reported rates of 0.3-1.8%). This complication arises from the artery's close proximity to the mitral annulus, particularly at the anterolateral commissure. The study aimed to assess this risk in a patient group prone to such injury. The surgical procedure utilized a minimally invasive approach and indocyanine green-based fluorescence imaging. This technique allows a real-time visualization of the circumflex artery, aiding precise placement of annular sutures and minimizing the risk of injury. The method, applied in 6 patients, integrates preoperative assessments with intraoperative fluorescence imaging, ensuring accurate arterial depiction and preventing iatrogenic damage. The study highlights the safety and efficacy of fluorescence imaging, especially in identifying vessel anomalies, indicating potential applications in various cardiac procedures., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

HIV is highly prevalent in men who have sex with men (MSM) in West Africa. Many MSM in the region also have sex with women (MSMW). Accordingly, they are a potential bridge subpopulation for HIV transmission to women. We aimed to evaluate the proportions and characteristics of West African MSMW at high behavioral risk of acquiring HIV from male partners and transmitting it to female partners (HBRMF). The cohort ANRS-12324 CohMSM Study included 630 HIV-negative MSM in Burkina Faso, Cote d'Ivoire, Mali, and Togo. Among MSMW (i.e., with ≥ 1 female partner) in the cohort, HBRMF was identified using trajectory models based on seven at-risk sexual practices with male and female partners, including inconsistent condom use, multiple partnerships, and receptive same-sex anal intercourse. To assess the relevance of using trajectory models, we compared the proportions of participants who seroconverted during the cohort follow-up among those at HBRMF and those not at HBRMF. Factors associated with HBRMF were identified using a generalized estimation equation logistic regression model accounting for longitudinal data. Approximately half (47%) of the 304 MSMW (22% of all CohMSM study participants) were at HBRMF. This group accounted for 75% of the 28 HIV seroconversions observed during follow-up (p = 0.001). HBRMF was positively associated with being aged < 25 years (aOR 95% CI 1.67 [1.23-2.27]), being sexually attracted only to men (1.97 [1.38-2.78]), feelings of loneliness (1.92 [1.38-2.65]), and homonegative violence score (1.22 [1.05-1.41]). HBRMF was negatively associated with having had both stable and casual female partners in the previous 6 months (0.34 [0.20-0.60] vs. only a stable female partner). HBRMF tended to be negatively associated with having ≥ 4 sexual intercourses with female partners in the previous four weeks (0.54 [0.27-1.06] vs. no intercourse). Establishing official relationships with women might be a strategy for young and/or stigmatized MSMW to comply with social pressure to display a heterosexual lifestyle. However, this seems to increase the risk of HIV transmission to female partners. In the present study, almost half of MSMW were at HBRMF. This result stresses the need to adapt HIV research and prevention to MSMW and their female partners., (© 2023. The Author(s).)

Optical interconnects have been recognized as the most promising solution to accelerate data transmission in the artificial intelligence era. Benefiting from their cost-effectiveness, compact dimensions, and wavelength multiplexing capability, silicon microring resonator modulators emerge as a compelling and scalable means for optical modulation. However, the inherent trade-off between bandwidth and modulation efficiency hinders the device performance. Here we demonstrate a dense wavelength division multiplexing microring modulator array on a silicon chip with a full data rate of 1 Tb/s. By harnessing the two individual p-n junctions with an optimized Z-shape doping profile, the inherent trade-off of silicon depletion-mode modulators is greatly mitigated, allowing for higher-speed modulation with energy consumption of sub-ten fJ/bit. This state-of-the-art demonstration shows that all-silicon modulators can practically enable future 200 Gb/s/lane optical interconnects., (© 2024. The Author(s).)

Between 15-20% of patients with end stage renal disease (ESRD) do not know the cause of the primary kidney disease and can develop complications after kidney transplantation. We performed a genetic screening in 300 patients with kidney transplantation, or undiagnosed primary renal disease, in order to identify the primary disease cause and discriminate between overlapping phenotypes. We used a custom-made panel for next-generation sequencing (Agilent technology, Santa Clara, CA, USA), including genes associated with Fabry disease, podocytopaties, complement-mediated nephropathies and Alport syndrome-related diseases. We detected candidate diagnostic variants in genes associated with nephrotic syndrome and Focal Segmental Glomerulosclerosis (FSGS) in 29 out of 300 patients, solving about 10% of the probands. We also identified the same genetic cause of the disease ( PAX2 : c.1266dupC) in three family members with different clinical diagnoses. Interestingly we also found one female patient carrying a novel missense variant, c.1259C>A (p.Thr420Lys), in the GLA gene not previously associated with Fabry disease, which is in silico defined as a likely pathogenic and destabilizing, and associated with a mild alteration in GLA enzymatic activity. The identification of the specific genetic background may provide an opportunity to evaluate the risk of recurrence of the primary disease, especially among patient candidates living with a donor kidney transplant.

Background: Despite advanced diagnosis and treatment, infective endocarditis (IE) is a potentially life-threatening condition. The impact of COVID-19 on the diagnosis and outcome of the surgical treatment of IE is uncertain. The aim of this study was to analyze the incidence, characteristics, and outcomes of surgically treated IE before and after the COVID-19 pandemic., Methods: This study retrospectively analyzed the data of 535 patients who underwent valve surgical procedures for IE between January 2010 and December 2022 in a single cardiac surgery center. Patients were divided into two groups depending on the date of their operation: before ( n = 393) and after ( n = 142) COVID-19 onset. In order to balance the groups, inverse probability of treatment weighting (IPTW) calculated from the propensity score (PS) was applied. Weighted univariate logistic regressions were reported for outcomes; weights were derived from IPTW. Interrupted time series analysis (ITSA) according to Linden's method was used to evaluate the changes in the manifestation of IE after 11 March 2020., Results: Patients from the post-COVID-19 cohort (after 11 March 2020) had a greater number of comorbidities such as diabetes (29.6% vs. 16.3% p = 0.001), hypertension (71.1% vs. 59.5% p = 0.015), and preoperative kidney injury requiring dialysis (9.2% vs. 2.5% p = 0.002), but the median additive and logistic EuroSCORE were not statistically different. In the post-COVID-19 group, we observed a greater prevalence of Staphylococcus aureus -related endocarditis (24.5% vs. 15.4% p = 0.026), a consequent reduction in Staphylococcus non aureus -related endocarditis (12.2% vs. 20.1% p = 0.048), and a decrease in aortic valve replacements (43.0% vs. 53.9%), while the number of mitral valve replacements and repair was greater (21.1% vs. 15.0% and 6.3% vs. 4.3%, respectively). No differences were found in the two groups concerning early death, death, or relapse at 1 year after surgery. Data obtained by multivariable analysis identified preoperative renal dysfunction requiring dialysis as the only common risk factor for early mortality via stratifying by time periods in analysis., Conclusions: The incidence of surgically treated IE significantly increases after the COVID-19 pandemic with a higher incidence of mitral valve involvement with respect to the aortic valve. Although a delay in surgical timing occurred during the COVID-19 pandemic, data in terms of mortality and outcomes were largely unaffected.

Background: TERT promoter mutation is one of the most common genomic alterations in urothelial carcinoma (UC). Its prognostic role on patients' outcomes is still not clear., Methods: We performed a single-center retrospective analysis on patients with advanced UC treated with platinum-based chemotherapy or immunotherapy to assess the presence of somatic TERT -124[C>T] and TERT -146[C>T] mutations and their association with clinicopathologic factors and survival outcomes. Patients were assessed for Overall Survival (OS), Progression-Free Survival (PFS), and Overall Response Rate (ORR)., Results: We analyzed 45 UC tumors; 38 of them received first-line chemotherapy and 21 second-line pembrolizumab; 6 patients (13%) harbored -146 C > T TERTp mutation and 25 patients (56%)-124 C > T. The presence of TERT promoter mutations was associated with a higher rate of lower tract UC and a lower rate of synchronous or lymph node metastases. TERT wild-type patients showed higher 12- and 24-months OS-rates in the chemotherapy subgroup and 6-, 12- and 24-months OS rates in the pembrolizumab subgroup. The presence of TERT promoter mutations was also associated with a lower 6 months-PFS rate in patients receiving chemotherapy and in all the three time points in those treated by pembrolizumab. The ORRs of pembrolizumab were 21% and 71% in patients with or without TERT promoter mutations, respectively (p < 0.001)., Conclusions: Our analysis suggests that the presence of TERT promoter mutations could negatively affect the outcome of UC patients treated by chemotherapy or pembrolizumab. This hypothesis should be further evaluated in wider cohorts., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Uremic toxins accumulate in patients affected by renal failure and can deposit in different organs, including the kidneys and heart. Given their physicochemical characteristics, uremic toxins can contribute to organ dysfunction due to several pathobiological actions at cellular and molecular levels. Several uremic compounds have been described in serum and plasma from patients with acute kidney injury (AKI) and kidney failure; they are usually classified based on their molecular size and protein-binding properties. In this scenario, new dialytic approaches have been proposed in the last few years with the aim of improving uremic toxin removal. Recent studies which focused on the use of medium cut-off membranes in patients on chronic hemodialysis have shown a discrete ability to remove β2-microglobulin and other middle molecules, such as kappa and lambda free light chains, complement factor D and α1-microglobulin. However, current evidence is mainly based on the impact on short-term outcomes and, consequently, longer observational studies are necessary to confirm the efficacy and safety of the medium cut-off dialyzer. Here we present the state-of-the-art on the clinical application of medium cut-off membranes in AKI and chronic dialysis patients., (© 2023. The Author(s).)

Most domestic servants (DS) in Mali are very young female migrants living in precarious conditions. We aimed to understand their living and working conditions in relation to their general and sexual health. Seven focus groups (53 participants) were conducted by the DS community-based organization ADDAD. Narratives were thematically analyzed using an inductive method. The dominant emerging theme was DS' strong dependence on their employers. Employers' attitudes regarding DS workload, the provision of food, water and hygiene products, housing conditions, and healthcare cover, appeared decisive for DS' physical and mental health, and the type of healthcare they used (self-medication, traditional care, healthcare facilities). Psychological, physical and sexual violence in employers' households was frequent. HIV/STI prevention knowledge was poor. These results highlight the serious risks for DS in terms of HIV/STI and unwanted pregnancies. DS were interested in receiving healthcare from ADDAD; this was motivated by the organization's trusting and understanding community-based environment, and DS' fear of discrimination in healthcare facilities. This study highlights the relevance of tackling the defense of rights and sexual health promotion for DS at the community level. Its findings can help identify research questions to evaluate the extent to which DS constitute a key HIV population.

Background: Nowadays, one of the main goals of aortic valve surgery is to reduce the biological impact, mortality, and complications. It is well-known that long operative times in terms of the extracorporeal circulation, but above all, of the aortic cross-clamp time (ACC), represent a risk factor for mortality in patients undergoing cardiac surgery. In order to shorten the aortic cross-clamp time, many technological improvements, such as sutureless prostheses, have been introduced, but their actual effectiveness has not been proven yet. The aim of this study was to assess the 30-day outcomes of patients undergoing aortic valve replacement surgery, focusing on the ACC length., Methods: All 3139 patients undergoing aortic valve replacement between January 2013 and July 2022 at our institution were enrolled. The data were retrospectively collected and the baseline characteristics and intraoperative variables were recorded. In order to adjust the results according to the differences in the baseline characteristics, propensity score matching was performed and four groups of 351 patients were obtained based on the first, second, third, and fourth quartile of the ACC time., Results: The patient population included 132 redo surgeries (9.4%) and 61 cases of active endocarditis (4.3%), with an overall median EuroSCORE II of 1.8 (IQR 1.2-3.1). An increase across the groups was observed in terms of the acute kidney failure ( p < 0.001) incidence, the number of blood transfusions ( p = 0.022), prolonged hospital stays ( p < 0.001), the and respiratory failure ( p < 0.001) incidence. A p of < 0.1 was found for the 30-day mortality ( p = 0.079). The predictors of an early 30-day mortality were standard full sternotomy (OR 2.48, 95% CI 1.14-5.40, p = 0.022), EuroSCORE II (OR 1.10, 95% CI 1.05-1.16, p < 0.001), and a trend for a longer ACC time (Q4 vs. Q1: OR 2.62, 95% CI 0.89-7.68, p = 0.080)., Conclusions: Shortening the operative times resulted in marked improvements of the patients' outcomes. The combined use of minimally invasive approaches and sutureless aortic valve prostheses allows for a lower 30-day events rate. New technologies should be assessed to obtain the best results with the least risk.

Background: Sepsis is characterized by a dysregulated immune response and metabolic alterations, including decreased high-density lipoprotein cholesterol (HDL-C) levels. HDL exhibits beneficial properties, such as lipopolysaccharides (LPS) scavenging, exerting anti-inflammatory effects and providing endothelial protection. We investigated the effects of CER-001, an engineered HDL-mimetic, in a swine model of LPS-induced acute kidney injury (AKI) and a Phase 2a clinical trial, aiming to better understand its molecular basis in systemic inflammation and renal function., Methods: We carried out a translational approach to study the effects of HDL administration on sepsis. Sterile systemic inflammation was induced in pigs by LPS infusion. Animals were randomized into LPS (n = 6), CER20 (single dose of CER-001 20 mg/kg; n = 6), and CER20 × 2 (two doses of CER-001 20 mg/kg; n = 6) groups. Survival rate, endothelial dysfunction biomarkers, pro-inflammatory mediators, LPS, and apolipoprotein A-I (ApoA-I) levels were assessed. Renal and liver histology and biochemistry were analyzed. Subsequently, we performed an open-label, randomized, dose-ranging (Phase 2a) study included 20 patients with sepsis due to intra-abdominal infection or urosepsis, randomized into Group A (conventional treatment, n = 5), Group B (CER-001 5 mg/kg BID, n = 5), Group C (CER-001 10 mg/kg BID, n = 5), and Group D (CER-001 20 mg/kg BID, n = 5). Primary outcomes were safety and efficacy in preventing AKI onset and severity; secondary outcomes include changes in inflammatory and endothelial dysfunction markers., Results: CER-001 increased median survival, reduced inflammatory mediators, complement activation, and endothelial dysfunction in endotoxemic pigs. It enhanced LPS elimination through the bile and preserved liver and renal parenchyma. In the clinical study, CER-001 was well-tolerated with no serious adverse events related to study treatment. Rapid ApoA-I normalization was associated with enhanced LPS removal and immunomodulation with improvement of clinical outcomes, independently of the type and gravity of the sepsis. CER-001-treated patients had reduced risk for the onset and progression to severe AKI (stage 2 or 3) and, in a subset of critically ill patients, a reduced need for organ support and shorter ICU length of stay., Conclusions: CER-001 shows promise as a therapeutic strategy for sepsis management, improving outcomes and mitigating inflammation and organ damage., Trial Registration: The study was approved by the Agenzia Italiana del Farmaco (AIFA) and by the Local Ethic Committee (N° EUDRACT 2020-004202-60, Protocol CER-001- SEP&#95;AKI&#95;01) and was added to the EU Clinical Trials Register on January 13, 2021., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The 2022 WHO classification of urinary and male genital tumors introduced several novel kidney entities exhibiting eosinophilic/oncocytic features with specific mutational backgrounds. Thus, molecular techniques, such as next-generation sequencing (NGS), became more commonly used for their evaluation. We studied 12 low-grade oncocytic tumors (LOT) of the kidney (from 11 patients), identified in a cohort of 210 eosinophilic/oncocytic renal tumors, diagnosed in our institution between October 2019 and May 2023, which represented 5.7% (12/210) of all eosinophilic/oncocytic renal tumors during this period. We reviewed their clinicopathologic, histologic, and immunohistochemical features, as well as their mutational profiles. We also reviewed the literature on NGS-derived data of LOT, by selecting papers in which LOT diagnosis was rendered according to the criteria proposed initially. Median age was 65 years (mean: 63.5; range 43-79) and median tumor size was 2.0 cm (mean: 2.2; range: 0.9-3.1). All tumors were positive for PAX8, CK7, and GATA3, and negative or focally positive for CD117/KIT. We found the following gene mutations: MTOR ((6/11), 54.5%)), TSC1 ((2/11), 18.2%)), and 1 had both NOTCH1 and NOTCH4 ((1/11), 9.1%)). Wild-type status was found in 2/11 (18.2%) patients and one tumor was not analyzable. A review of 8 previous studies that included 79 LOTs revealed frequent mutations in the genes that regulate the mammalian target of rapamycin (mTOR) pathway: MTOR (32/79 (40.5%)), TSC1 (21/79 (26.6%)), and TSC2 (9/79 (11.4%)). Other mutated genes included PIK3CA, NF2, and PTEN, not typically known to affect the mTOR pathway, but potentially acting as upstream and downstream effectors. Our study shows that LOT is increasingly diagnosed in routine practice when applying the appropriate diagnostic criteria. We also confirm that the mTOR pathway is strongly implicated in the pathogenesis of this tumor mainly through MTOR, TCS1, and TSC2 mutations, but other genes could also be involved in the pathway activation, especially in LOTs without "canonical" mutations., (© 2023. The Author(s).)

The creation and management of content are among the main open issues for the spread of Augmented Reality. In Augmented Reality interfaces for procedural tasks, a key authoring strategy is chunking instructions and using optimized visual cues, i.e., tailored to the specific information to convey. Nevertheless, research works rarely present rationales behind their choice. This work aims to provide design guidelines for the localization of in-view and not occluded components, which is recurrent information in technical documentation. Previous studies revealed that the most suited visual cues to convey this information are auxiliary models, i.e., abstract shapes that highlight the space region where the component is located. Among them, 3D arrows are widely used, but they may produce ambiguity of information. Furthermore, from the literature, it is unclear how to design auxiliary model shapes and if they are affected by the component shapes. To fill this gap, we conducted two user studies. In the first study, we collected the preference of 45 users regarding the shape, color, and animation of auxiliary models for the localization of various component shapes. According to the results of this study, we defined guidelines for designing optimized auxiliary models based on the component shapes. In the second user study, we validated these guidelines by evaluating the performance (localization time and recognition accuracy) and user experience of 24 users. The results of this study allowed us to confirm that designing auxiliary models following our guidelines leads to a higher recognition accuracy and user experience than using 3D arrows.

In this paper, we combine a Content-Addressable Memory (CAM) encoding scheme previously proposed for analog electronic CAMs (E-CAMs) with optical multiplexing techniques to create two new photonic CAM architectures-wavelength-division multiplexing (WDM) optical ternary CAM (O-TCAM) and time-division multiplexing (TDM) O-TCAM. As an example, we show how these two O-TCAM schemes can be implemented by performing minor modifications in microring-based silicon photonic (SiPh) circuits originally optimized for exascale interconnects. Here, our SiPh O-TCAM designs include not only the actual search engine, but also the transmitter circuits. For the first time, we experimentally demonstrate O-TCAM functionality in SiPh up to ∼ 4 Gbps and we prove in simulation feasibility for speeds up to 10 Gbps, 10 times faster than typical E-TCAMs at the expense of higher energy consumption per symbol of our O-TCAM Search Engine circuits than the corresponding E-TCAMs. Finally, we identify which hardware and architecture modifications are required to improve the O-CAM's energy efficiency towards the level of E-CAMs., Competing Interests: Conflict of interest: This work has been done during the employment of the authors at Hewlett Packard Labs, Milpitas, CA 95035, USA. As part of this work, the following patents have been issued [57–59]: US11057143B1, US11200929B1, US20220059147A1., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Diabetic nephropathy (DN) and non-diabetic renal diseases (NDRD) represent intricate challenges in diagnosis and treatment within the context of the global diabetes epidemic. As the prevalence of diabetes continues to escalate, effective management of renal complications becomes paramount. Recent advancements in comprehending the multifaceted nature of renal damage, fueled by insights from histopathological investigations, offer unprecedented prospects for refining diagnostic strategies and customizing therapeutic interventions. Renal biopsies have emerged as indispensable tools for unraveling the diverse phenotypes of renal damage in diabetes. The pioneering study by Mazzucco identified three classes of renal damage in type 2 diabetes patients: classical diabetic glomerulosclerosis (DN), vascular and ischemic glomerular changes (NDRD), and other glomerulonephritides in the presence (DN + NDRD, mixed forms) or absence of DN (NDRD). The prevalence of these classes varies widely in published studies, influenced by factors such as ethnicity, geography and selection criteria for renal biopsy. Moreover, the international Renal Pathology Society consensus classification system has stratified the classical diabetic nephropathy into progressive categories of renal impairment, a breakthrough that aids in prognostication. Histopathological scrutiny, particularly the intricate correlation between glomerular and tubulointerstitial lesions, contributes profoundly to enhancing our grasp of the phenotype's heterogeneity. This amplified comprehension holds the potential to steer personalized treatment strategies. Cutting-edge interventions, encompassing sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists and anti-endothelin receptor agents, are broadening the arsenal against renal injury in diabetes. When combined with the profound insights garnered from histopathological, omics, imaging and clinical data, these therapeutic avenues promise a transformative shift towards precision-driven care paradigms. Collaborative efforts uniting researchers, clinicians and patients are indispensable for propelling our knowledge of diabetic renal damage and ameliorating patient outcomes. The fusion of histopathological, omics and imaging findings into clinical decision-making harbors the potential to customize interventions and optimize care for individuals grappling with diabetes-associated renal complications. Furthermore, groundbreaking initiatives like the iBeat Study within the BEAt-DKD (Biomarker Enterprise to Attack Diabetic Kidney Disease) project (https://www.beat-dkd.eu/), elucidating distinct phenotypes of renal damage within diabetes, underscore the imperative necessity of integrating histopathological data into the broader framework of diabetic renal management., Competing Interests: L.G. received grant support from Abionyx and Sanofi to his university department (DIMEPRE-J); he has been a member of advisory boards for AstraZeneca, Baxter, Chinook, GSK, Mundipharma, Novartis, Pharmadoc, Roche, Sanofi, Travere and Vifor Pharma, and an invited speaker at meetings supported by AstraZeneca, Astellas, Estor, Fresenius, Werfen, Medtronic, Travere and GSK. P.P. has been a member of an advisory board for Sanofi and was an invited speaker at meetings supported by Werfen and Estor. M.F. has been an invited speaker at meetings supported by AstraZeneca, Bayer, Estor and bioMerieux., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: Percutaneous renal biopsy (PRB) may subject patients to emotional distress and pain before and during the biopsy. The aim of this study was to evaluate the effects of complementary/non-pharmacological interventions such as music therapy (MT) on anxiety, pain and satisfaction in renal patients undergoing PRB., Methods: A prospective, single-centre, single-blind, randomized controlled two-arm trial was conducted. Patients ≥18 years of age, hospitalized at the Nephrology, Dialysis and Transplantation Unit (Bari, Italy) and scheduled for PRB were screened. Participants were assigned to standard treatment (CG) or to the music therapy (MT) intervention group. Participants in the MT group received standard care and an MT intervention by a certified music therapist qualified in guided imagery and music. The CG patients received the standard of care. MT and CG patients were subjected to identical measurements (pre/post) of the parameters in the State Trait Anxiety Inventory Y1 (STAI-Y1), visual analogue scale for pain (VAS-P) and satisfaction (VAS-S) and heart rate variability., Results: A statistically significant difference in the anxiety scores after PRB between MT and CG patients (STAI-Y1 35.4 ± 6.2 versus 42.9 ± 9.0) was observed. MT also had strong and significant effects on VAS-P compared with CG (5.0 ± 1.4 versus 6.3 ± 1.3, respectively; P  < .001) and VAS-S (7.8 ± 1.0 versus 6.0 ± 0.9, respectively; P  < .001). Decreased activity of the sympathetic nervous system and increased activity of the parasympathetic nervous system was observed after PRB in the MT group., Conclusion: Our study supports the use of MT to mitigate the psychological anxiety, pain and sympathetic activation associated with PRB., Competing Interests: The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Introduction: Prostate cancer (PCa) is the most frequent tumor among men in Europe and has both indolent and aggressive forms. There are several treatment options, the choice of which depends on multiple factors. To further improve current prognostication models, we established the Turin Prostate Cancer Prognostication (TPCP) cohort, an Italian retrospective biopsy cohort of patients with PCa and long-term follow-up. This work presents this new cohort with its main characteristics and the distributions of some of its core variables, along with its potential contributions to PCa research., Methods: The TPCP cohort includes consecutive non-metastatic patients with first positive biopsy for PCa performed between 2008 and 2013 at the main hospital in Turin, Italy. The follow-up ended on December 31 st 2021. The primary outcome is the occurrence of metastasis; death from PCa and overall mortality are the secondary outcomes. In addition to numerous clinical variables, the study's prognostic variables include histopathologic information assigned by a centralized uropathology review using a digital pathology software system specialized for the study of PCa, tumor DNA methylation in candidate genes, and features extracted from digitized slide images via Deep Neural Networks., Results: The cohort includes 891 patients followed-up for a median time of 10 years. During this period, 97 patients had progression to metastatic disease and 301 died; of these, 56 died from PCa. In total, 65.3% of the cohort has a Gleason score less than or equal to 3 + 4, and 44.5% has a clinical stage cT1. Consistent with previous studies, age and clinical stage at diagnosis are important prognostic factors: the crude cumulative incidence of metastatic disease during the 14-years of follow-up increases from 9.1% among patients younger than 64 to 16.2% for patients in the age group of 75-84, and from 6.1% for cT1 stage to 27.9% in cT3 stage., Discussion: This study stands to be an important resource for updating existing prognostic models for PCa on an Italian cohort. In addition, the integrated collection of multi-modal data will allow development and/or validation of new models including new histopathological, digital, and molecular markers, with the goal of better directing clinical decisions to manage patients with PCa., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Destefanis, Fiano, Milani, Vasapolli, Fiorentino, Giunchi, Lianas, Del Rio, Frexia, Pireddu, Molinaro, Cassoni, Papotti, Gontero, Calleris, Oderda, Ricardi, Iorio, Fariselli, Isaevska, Akre, Zelic, Pettersson, Zugna and Richiardi.)

Bimonthly long-acting injectable pre-exposure prophylaxis (LAI-PrEP) can become an important additional tool for HIV prevention among West African men who have sex with men (MSM). The objective was to explore the perceived added value of LAI-PrEP as an HIV prevention tool among MSM in Burkina Faso, Côte d'Ivoire, Mali, and Togo. We conducted eight focus group discussions among 62 HIV-negative MSM between April and May 2021. Participants were recruited via local community-based clinics. Data collection and analysis were guided by grounded theory and community-based participatory approaches. Participants were generally knowledgeable about HIV, and explained particular barriers for HIV prevention in their communities (e.g., denial of HIV). The added value of LAI-PrEP relative to condoms was similar to oral pre-exposure prophylaxis (PrEP) in terms of perceived advantages (e.g., improved sexual satisfaction) or disadvantages (e.g., no protection against other sexually transmitted infections). Compared with oral PrEP, LAI-PrEP was perceived to provide better protection against HIV and to be more convenient (e.g., no need to be mindful of intake and less risk for stigma). Concerns included fear of needles, doubts about efficacy, potential side effects, and difficulties for ensuring timely injections (e.g., when traveling abroad). The results demonstrate that injectable PrEP can be of particular interest to subgroups of West African MSM, although existing HIV prevention tools such as condoms and oral PrEP will remain valuable alongside of, or instead of, LAI-PrEP. Increasing awareness about HIV and tackling discrimination based on sexual orientation continue to be crucial factors to be addressed for HIV prevention.

The intestinal barrier comprises a single layer of epithelial cells tightly joined to form a physical barrier. Disruption or compromise of the intestinal barrier can lead to the inadvertent activation of immune cells, potentially causing an increased risk of chronic inflammation in various tissues. Recent research has suggested that specific dietary components may influence the function of the intestinal barrier, potentially offering a means to prevent or mitigate inflammatory disorders. However, the precise mechanism underlying these effects remains unclear. Bovine colostrum (BC), the first milk from cows after calving, is a natural source of nutrients with immunomodulatory, anti-inflammatory, and gut-barrier fortifying properties. This novel study sought to investigate the transcriptome in BC-treated Zonulin transgenic mice (Ztm), characterized by dysbiotic microbiota, intestinal hyperpermeability, and mild hyperactivity, applying RNA sequencing. Seventy-five tissue samples from the duodenum, colon, and brain of Ztm and wild-type (WT) mice were dissected, processed, and RNA sequenced. The expression profiles were analyzed and integrated to identify differentially expressed genes (DEGs) and differentially expressed transcripts (DETs). These were then further examined using bioinformatics tools. RNA-seq analysis identified 1298 DEGs and 20,952 DETs in the paired (Ztm treatment vs. Ztm control) and reference (WT controls) groups. Of these, 733 DEGs and 10,476 DETs were upregulated, while 565 DEGs and 6097 DETs were downregulated. BC-treated Ztm female mice showed significant upregulation of cingulin ( Cgn ) and claudin 12 ( Cldn12 ) duodenum and protein interactions, as well as molecular pathways and interactions pertaining to tight junctions, while BC-treated Ztm males displayed an upregulation of transcripts like occludin ( Ocln ) and Rho/Rac guanine nucleotide exchange factor 2 ( Arhgf2 ) and cellular structures and interfaces, protein-protein interactions, and organization and response mechanisms. This comprehensive analysis reveals the influence of BC treatment on tight junctions (TJs) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway gene expressions. The present study is the first to analyze intestinal and brain samples from BC-treated Ztm mice applying high-throughput RNA sequencing. This study revealed molecular interaction in intestinal barrier function and identified hub genes and their functional pathways and biological processes in response to BC treatment in Ztm mice. Further research is needed to validate these findings and explore their implications for dietary interventions aimed at improving intestinal barrier integrity and function. The MGH Institutional Animal Care and Use Committee authorized the animal study (2013N000013).

Introduction: There is a paradigm shift in our understanding of white matter hyperintensities (WMH) found on brain imaging. They were once thought to be a normal phenomenon of ageing and, therefore, warranted no further investigation. However, evidence now suggests these lesions are markers of poor brain and cardiovascular health, portending an increased risk of stroke, cognitive decline, depression and death. Nevertheless, no specific guidelines exist for the management of incidentally found WMH for general medical practitioners and other clinicians ordering brain magnetic resonance imaging scans for diverse clinical indications. Informed by a literature review and expert opinion gleaned from stroke neurologists, medical and imaging specialists, and general practitioners, we present our consensus statement to guide the management of incidentally found WMH in adults., Main Recommendations: When incidental WMH are found on brain imaging: Perform a detailed history and examination to screen for neurological events. Investigate for potential undiagnosed or undertreated cardiovascular risk factors, especially hypertension and diabetes mellitus. Commence intensive and individualised cardiovascular risk management when risk factors are uncovered. Treat underlying risk factors via accepted guidelines but note that antiplatelet and anticoagulant medications should not be prescribed for incidental WMH in the absence of an alternative indication., Changes to Management as a Result of This Consensus Statement: A brain health opportunity. We consider the discovery of incidental WMH on brain imaging to represent an opportunity to investigate for common cardiovascular risk factors and to optimise brain health. This can be commenced and monitored by the general practitioner or physician without delay in waiting for an outpatient neurology review., (© 2023 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Introduction: Frailty in trauma has been found to predict poor outcomes after injury including additional in-hospital complications, mortality, and discharge to dependent care. These gross outcome measures are insufficient when discussing long-term recovery as they do not address what is important to patients including functional status and quality of life. The purpose of this study is to determine if the Palliative Performance Scale (PPS) predicts mortality and functional status one year after trauma in geriatric patients., Material and Methods: Prospective observational study of trauma survivors, age ≥55 years. Patients were stratified by pre-injury PPS high (>70) or low (≤70). Outcomes were functional status at 1 year measured by Glasgow Outcome Scale Extended (GOSE), Euroqol-5D and SF-36. Adjusted relative risks (aRR) were obtained using modified Poisson regression., Results: Follow-up was achieved on 215/301 patients. Mortality was 30% in low PPS group vs 8% in the high PPS group (P<0.001). A greater percentage of patients in the high group had a good functional outcome at one year compared to patients in the low group (78% vs 30% p<0.001). The high PPS patients were more likely to have improvement of GOSE at 1 year from discharge compared to low group (66% vs 27% P<0.001). Low PPS independently predicted poor functional outcome (aRR, 2.64; 95% confidence interval, 1.79-3.89) and death at 1 year (aRR, 3.64; 95% confidence interval 1.68-7.92). An increased percentage of low PPS patients reported difficulty with mobility (91% vs 46% p<0.0001) and usual activities (82% vs 56% p=0.002). Both groups reported pain (65%) and anxiety/depression (47%)., Conclusion: Low pre-Injury PPS predicts mortality and poor functional outcomes one year after trauma. Low PPS patients were more likely to decline, rather than improve. Regardless of PPS, most patients have persistent pain, anxiety, and limitations in performing daily activities., Competing Interests: Declaration of Competing Interest None of the authors the authors have any personal conflicts of interest with the material Support for this publication was provided by the Auen Foundation (Dr. Fiorentino and Dr. Hwang. Grant Numbers A18-63/A16-88), (Copyright © 2023. Published by Elsevier Ltd.)

Adverse neighborhood social and natural (green space) environments may contribute to the etiology of prostate cancer (CaP), but mechanisms are unclear. We examined associations between neighborhood environment and prostate intratumoral inflammation in 967 men diagnosed with CaP with available tissue samples from 1986-2009 in the Health Professionals Follow-up Study. Exposures were linked to work or residential addresses in 1988. We estimated indices of neighborhood socioeconomic status (nSES) and segregation (Index of Concentration at the Extremes (ICE)) using US Census tract-level data. Surrounding greenness was estimated using seasonal averaged Normalized Difference Vegetation Index (NDVI) data. Surgical tissue underwent pathological review for acute and chronic inflammation, corpora amylacea, and focal atrophic lesions. Adjusted odds ratios (aORs) for inflammation (ordinal) and focal atrophy (binary) were estimated using logistic regression. No associations were observed for acute or chronic inflammation. Each interquartile-range increase in NDVI within 1,230 m of the participant's work or home address (aOR = 0.74, 95% confidence interval (CI): 0.59, 0.93), in ICE-income (aOR = 0.79, 95% CI: 0.61, 1.04), and in ICE-race/income (aOR = 0.79, 95% CI: 0.63, 0.99) was associated with lower odds of postatrophic hyperplasia. Interquartile-range increases in nSES (aOR = 0.76, 95% CI: 0.57, 1.02) and ICE-race/income (aOR = 0.73, 95% CI: 0.54, 0.99) were associated with lower odds of tumor corpora amylacea. Histopathological inflammatory features of prostate tumors may be influenced by neighborhood., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)