University of Verona

Aim Renal leiomyoma is a rare benign mesenchymal tumor arising from the smooth muscle cells of the kidney. Renal capsule is its most common location (¹1 Aldughiman AW, Alzahrani A, Alzahrani T. Renal Leiomyoma: Case Report and Literature Review. J Endourol Case Rep. 2019;5:181-3.). Large tumor may require surgical excision which can be challenging in case of proximity to major vessels (²2 Filianoti A, Paganelli A, Bassi P, Simone G, Ranieri A. Leiomyoma of the renal capsule: case report and literature review. Urologia. 2018;85:34-5.). Indications of robotic partial nephrectomy (RPN) have exponentially expanded over the past few years (³3 Cerrato C, Patel D, Autorino R, Simone G, Yang B, Uzzo R, et al. Partial or radical nephrectomy for complex renal mass: a comparative analysis of oncological outcomes and complications from the ROSULA (Robotic Surgery for Large Renal Mass) Collaborative Group. World J Urol. 2023;41:747-55.). We aim to report a case of large renal leiomyoma successfully managed with RPN. Methods A 59-year-old female patient with BMI 51 presented with chief complaint of abdominal discomfort. The patient underwent a CT scan that revealed a massive circumscribed exophytic complex solid cystic mass of 4.5 × 7.7 × 6.2 cm, arising from the lower pole of right kidney and abutting the inferior vena cava. RENAL score was 11ah (high complexity). Past surgical history included mid-urethral sling, breast reduction, and hysterectomy with salpingectomy. Preoperative creatinine and eGFR were 0.9 (mg/dL) and 77 (mL/min), respectively. A robotic excision of this mass was successfully performed by using Da Vinci Xi platform. Main steps of the procedure are illustrated in the present video. Results Dissection and isolation of the tumor were carefully performed after identifying key anatomical structures such as the ureter, the IVC and the renal hilum. Intraoperative ultrasound was used to confirm the margins of the mass. The renal artery was clamped and then the tumor was resected/enucleated. Renal parenchyma was re-approximated with a single layer of interrupted CT-1 Vicryl 0 with sliding clip technique. Warm ischemia time was 19 min. Estimated blood loss (EBL) was 250 ml. Operative time was 165 min. No intraoperative complications occurred. No drain was placed. Patient was discharged on postoperative day 2. Post-operative hypotension was managed with fluid bolus. Postoperative creatinine and eGFR were 1,0 (mg/dL) and 69 (mL/min/1.72m²), respectively. Pathology revealed a leiomyoma of genital stromal origin with hyalinization and calcification. Conclusions To the best of our knowledge, this is the first description of RPN for the management of a large (about 8 cm) renal leiomyoma. Robotic assisted surgery allows to expand the indications of minimally invasive conservative renal surgery whose feasibility becomes even more clinically significant in case of benign masses which can be managed without sacrificing healthy renal parenchyma.

Introduction Intraoperative neurophysiology (ION) has been established over the past three decades as a valuable discipline to improve the safety of neurosurgical procedures with the main goal of reducing neurological morbidity. Neurosurgeons have substantially contributed to the development of this field not only by implementing the use and refinement of ION in the operating room but also by introducing novel techniques for both mapping and monitoring of neural pathways. Methods This review provides a personal perspective on the evolution of ION in a variety of pediatric neurosurgical procedures: from brain tumor to brainstem surgery, from spinal cord tumor to tethered cord surgery. Results and discussion The contribution of pediatric neurosurgeons is highlighted showing how our discipline has played a crucial role in promoting ION at the turn of the century. Finally, a view on novel ION techniques and their potential implications for pediatric neurosurgery will provide insights into the future of ION, further supporting the view of a functional, rather than merely anatomical, approach to pediatric neurosurgery.

Objective Fruit set is triggered after ovule fertilization, as a consequence of the downregulation of ovary growth repressors, such as the tomato transcription factors Auxin/indole-3-acetic acid 9 (IAA9) and Agamous-like 6 (AGL6). In a recent work, we developed a method to silence IAA9 and AGL6 in tomato ovaries using exogenous dsRNAs. We also produced small RNA libraries from IAA9- and AGL6-silenced ovaries to confirm the presence of siRNAs, derived from exogenous dsRNA, targeting IAA9 and AGL6. The objective of this work is to exploit these sRNA libraries to identify miRNAs differentially expressed in IAA9- and AGL6-silenced ovaries as compared with unpollinated control ovaries. Results We identified by RNA sequencing 125 and 104 known and 509 and 516 novel miRNAs from reads mapped to mature or hairpin sequences, respectively. Of the known miRNAs, 7 and 45 were differentially expressed in IAA9- and AGL6-silenced ovaries compared to control ones, respectively. Six miRNAs were common to both datasets, suggesting their importance in the fruit set process. The expression pattern of two of these (miR393 and miR482e-5p) was verified by stem-loop qRT-PCR. The identified miRNAs represent a pool of regulatory sRNAs potentially involved in tomato fruit initiation.

Patients with hepatocellular carcinoma (HCC) may have a heterogeneous presentation, as well as different long-term outcomes following surgical resection. We sought to use machine learning to cluster patients into different prognostic groups based on preoperative characteristics. Patients who underwent curative-intent liver resection for HCC between 2000 and 2020 were identified from a large international multi-institutional database. A hierarchical cluster analysis was performed based on preoperative factors to characterize patterns of presentation and define disease-free survival (DFS). Among 966 with HCC, 3 distinct clusters were identified: Cluster 1 (n = 160, 16.5%), Cluster 2 (n = 537, 55.6%) and Cluster 3 (n = 269, 27.8%). Cluster 1 (n = 160, 16.5%) consisted of female patients (n = 160, 100%), low inflammation-based scores, intermediate tumor burden score (TBS) (median: 4.71) and high alpha-fetoprotein (AFP) levels (median 41.3 ng/mL); Cluster 2 consisted of male individuals (n = 537, 100%), mainly with a history of HBV infection (n = 429, 79.9%), low inflammation-based scores, intermediate AFP levels (median 26.0 ng/mL) and lower TBS (median 4.49); Cluster 3 was comprised of older patients (median age 68 years) predominantly male (n = 248, 92.2%) who had low incidence of HBV/HCV infection (7.1% and 8.2%, respectively), intermediate AFP levels (median 16.8 ng/mL), high inflammation-based scores and high TBS (median 6.58). Median DFS worsened incrementally among the three different clusters with Cluster 3 having the lowest DFS (Cluster 1: median not reached; Cluster 2: 34 months, 95% CI 23.0–48.0, Cluster 3: 19 months, 95% CI 15.0–29.0, p < 0.05). Cluster analysis classified HCC patients into three distinct prognostic groups. Cluster assignment predicted DFS following resection of HCC with the female cluster having the most favorable prognosis following HCC resection.

Interpretation of laboratory data is a comparative procedure and requires reliable reference data, which are mostly derived from population data but used for individuals in conventional laboratory medicine. Using population data as a "reference" for individuals has generated several problems related to diagnosing, monitoring, and treating single individuals. This issue can be resolved by using data from individuals' repeated samples, as their personal reference, thus needing that laboratory data be personalized. The modern laboratory information system (LIS) can store the results of repeated measurements from millions of individuals. These data can then be analyzed to generate a variety of personalized reference data sets for numerous comparisons. In this manuscript, we redefine the term "personalized laboratory medicine" as the practices based on individual-specific samples and data. These reflect their unique biological characteristics, encompassing omics data, clinical chemistry, endocrinology, hematology, coagu-lation, and within-person biological variation of all laboratory data. It also includes information about individuals' health behavior, chronotypes, and all statistical algorithms used to make precise decisions. This approach facilitates more accurate diagnosis, monitoring, and treatment of diseases for each individual. Furthermore, we explore recent advancements and future challenges of personalized laboratory medicine in the context of the digital health era.

Central B cell tolerance is believed to be regulated by B cell receptor signaling induced by the recognition of self-antigens in immature B cells. Using humanized mice with defective MyD88, TLR7, or TLR9 expression, we demonstrate that TLR9/MYD88 are required for central B cell tolerance and the removal of developing autoreactive clones. We also show that CXCL4, a chemokine involved in systemic sclerosis (SSc), abrogates TLR9 function in B cells by sequestering TLR9 ligands away from the endosomal compartments where this receptor resides. The in vivo production of CXCL4 thereby impedes both TLR9 responses in B cells and the establishment of central B cell tolerance. We conclude that TLR9 plays an essential early tolerogenic function required for the establishment of central B cell tolerance and that correcting defective TLR9 function in B cells from SSc patients may represent a novel therapeutic strategy to restore B cell tolerance.

Almost every novel by Charles Dickens could be said to expose the ideological blinders we willingly wear to live within certain ideological state apparatuses, such as the court of law in Bleak House or a debtor’s prison in Little Dorrit. But his primary and most consistent focus is on the most powerful of these structural apparatuses surrounding children, the family. Fully peopled by some of the most iconic child characters in Anglophone literature, the work of Charles Dickens also depicts diverse scenarios for recognising dysfunctional private families and alternative social solutions to childcare. In Oliver Twist and Great Expectations, Dickens cloaks the childcare question in the language of food—emotional, prosocial, substantial, and, most of all, not biologically but culturally created. Dickens seems to present a view of family that can be cobbled from community. Those characters who depend upon such “family” find themselves fed “by hand” in a social, not bio-kinship context, and by doing so, they might help us to question the biological essentialism that dominates familialist thought, oppresses women who mother, and abandons children to the uncertain supports of the private, domestic, family.

The treatment of bilateral vocal fold paralysis is mainly surgical and several procedures can be used to guarantee adequate breathing. Furthermore, other causes of the narrowing of the natural airways could coexist and the treatment should consider all of them. A supraglottic extension of posterior cordectomy to the false homolateral chord is described, which provides a further widening of the airway while maintaining acceptable voice quality. Endoscopic posterior ventricular cordectomy performed by contact diode laser may be a viable and safe option, especially in those patients who present bilateral vocal fold paralysis associated with various degrees of laryngospasm.

When exercising above the lactic threshold (LT), the slow component of oxygen uptake (\(\dot{V}{\text{O}}_{{{\text{2sc}}}}\)) appears, mainly ascribed to the progressive recruitment of Type II fibers. However, also the progressive decay of the economy of contraction may contribute to it. We investigated oxygen uptake (\(\dot{V}{\text{O}}_{{2}}\)) during isometric contractions clamping torque (T) or muscular activation to quantify the contributions of the two mechanisms. We assessed for 7 min T of the leg extensors, net oxygen uptake (\(\dot{V}{\text{O}}_{{{\text{2net}}}}\)) and root mean square (RMS) from vastus lateralis (VL) in 11 volunteers (21 ± 2 yy; 1.73 ± 0.11 m; 67 ± 14 kg) during cyclic isometric contractions (contraction/relaxation 5 s/5 s): (i) at 65% of maximal voluntary contraction (MVC) (FB-Torque) and; (ii) keeping the level of RMS equal to that at 65% of MVC (FB-EMG). \(\dot{V}{\text{O}}_{{{\text{2net}}}}\) after the third minute in FB-Torque increased with time (\(\dot{V}{\text{O}}_{{{\text{2net}}}}\) = 94 × t + 564; R2 = 0.99; P = 0.001), but not during FB-EMG. \(\dot{V}{\text{O}}_{{{\text{2net}}}}\)/T increased only during FB-Torque (\(\dot{V}{\text{O}}_{{{\text{2net}}}}\)/T = 1.10 × t + 0.57; R2 = 0.99; P = 0.001). RMS was larger in FB-Torque than in FB-EMG and significantly increased in the first three minutes of exercise to stabilize till the end of the trial, indicating that the pool of recruited MUs remained constant despite \(\dot{V}{\text{O}}_{{{\text{2sc}}}}\). The analysis of the RMS, \(\dot{V}{\text{O}}_{{2}}\) and T during FB-Torque suggests that the intrinsic mechanism attributable to the decay of contraction efficiency was responsible for an increase of \(\dot{V}{\text{O}}_{{{\text{2net}}}}\) equal to 18% of the total \(\dot{V}{\text{O}}_{{{\text{2sc}}}}\).

Quantum neural networks hold significant promise for numerous applications, particularly as they can be executed on the current generation of quantum hardware. However, due to limited qubits or hardware noise, conducting large-scale experiments often requires significant resources. Moreover, the output of the model is susceptible to corruption by quantum hardware noise. To address this issue, we propose the use of ensemble techniques, which involve constructing a single machine learning model based on multiple instances of quantum neural networks. In particular, we implement bagging and AdaBoost techniques, with different data loading configurations, and evaluate their performance on both synthetic and real-world classification and regression tasks. To assess the potential performance improvement under different environments, we conducted experiments on both simulated, noiseless software and IBM superconducting-based QPUs, suggesting these techniques can mitigate the quantum hardware noise. Additionally, we quantify the amount of resources saved using these ensemble techniques. Our findings indicate that these methods enable the construction of large, powerful models even on relatively small quantum devices.

Hyperkalemia is common in clinical practice and can be caused by medications used to treat cardiovascular diseases, particularly renin–angiotensin–aldosterone system inhibitors (RAASis). This narrative review discusses the epidemiology, etiology, and consequences of hyperkalemia, and recommends strategies for the prevention and management of hyperkalemia, mainly focusing on guideline recommendations, while recognizing the gaps or differences between the guidelines. Available evidence emphasizes the importance of healthcare professionals (HCPs) taking a proactive approach to hyperkalemia management by prioritizing patient identification and acknowledging that hyperkalemia is often a long-term condition requiring ongoing treatment. Given the risk of hyperkalemia during RAASi treatment, it is advisable to monitor serum potassium levels prior to initiating these treatments, and then regularly throughout treatment. If RAASi therapy is indicated in patients with cardiorenal disease, HCPs should first treat chronic hyperkalemia before reducing the dose or discontinuing RAASis, as reduction or interruption of RAASi treatment can increase the risk of adverse cardiovascular and renal outcomes or death. Moreover, management of hyperkalemia should involve the use of newer potassium binders, such as sodium zirconium cyclosilicate or patiromer, as these agents can effectively enable optimal RAASi treatment. Finally, patients should receive education regarding hyperkalemia, the risks of discontinuing their current treatments, and need to avoid excessive dietary potassium intake.

This paper presents a new approach to an old problem, the provincial reception of the image of Roman emperors. Applying 3D computer modelling, we captured the portrait features of Hadrian as represented on coinage minted for the British province, produced a 3D model from a coin and compared it with the bronze head of Hadrian found in London. The aim was to test the possibility, previously posited by other scholars, that the London portrait might have been produced by an artisan who used coin portraits of the emperor as his main – if not only – model. More generally, the paper examines the dependencies of coinage and sculpture on shared models and applies new technology to Roman portrait studies.

Introduction Artificial intelligence (AI) integration in nephropathology has been growing rapidly in recent years, facing several challenges including the wide range of histological techniques used, the low occurrence of certain diseases, and the need for data sharing. This narrative review retraces the history of AI in nephropathology and provides insights into potential future developments. Methods Electronic searches in PubMed-MEDLINE and Embase were made to extract pertinent articles from the literature. Works about automated image analysis or the application of an AI algorithm on non-neoplastic kidney histological samples were included and analyzed to extract information such as publication year, AI task, and learning type. Prepublication servers and reviews were not included. Results Seventy-six (76) original research articles were selected. Most of the studies were conducted in the United States in the last 7 years. To date, research has been mainly conducted on relatively easy tasks, like single-stain glomerular segmentation. However, there is a trend towards developing more complex tasks such as glomerular multi-stain classification. Conclusion Deep learning has been used to identify patterns in complex histopathology data and looks promising for the comprehensive assessment of renal biopsy, through the use of multiple stains and virtual staining techniques. Hybrid and collaborative learning approaches have also been explored to utilize large amounts of unlabeled data. A diverse team of experts, including nephropathologists, computer scientists, and clinicians, is crucial for the development of AI systems for nephropathology. Collaborative efforts among multidisciplinary experts result in clinically relevant and effective AI tools. Graphical abstract

Background Biological DMARDs (bDMARDs) have been proven to prevent joint damage and bone erosions. Nevertheless, approximately 15% of rheumatoid arthritis (RA) patients on bDMARDs will progress despite good control of joint inflammation. Objectives The objective of our study is to investigate the factors associated with radiological progression of patients treated with bDMARDs. Design We conducted a retrospective analysis of longitudinally collected data on RA patients starting bDMARDs. Methods Presence or development of new erosions was assessed by a skilled rheumatologist at the time of the visit (baseline and 12 months thereafter). To determine the predictors of erosions, we employed multivariable logistic regression models. Discriminatory capacity for the prediction of new erosion development was assessed with receiver operating characteristic (ROC) curve, which was based on the logistic regression model. Results A total of 578 RA patients starting bDMARDs were included in the study. Overall, 46 patients (approximately 10%) had radiographic progression (at least one new erosion) at 12 months of follow-up. The factors independently associated with higher risk of developing new erosions while on bDMARD were younger age, high disease activity at baseline, not being treated with cDMARDs, and presenting with erosions at baseline. In addition, we built a predictive model that can accurately foresee new erosions (AUC 0.846) in patients receiving bDMARDs Conclusion We found that baseline erosive disease, higher disease activity during treatment, younger age, and monotherapy were the factors independently associated with the development of bone erosions. Our study may inform future targeted intervention in RA patients at risk of radiographic progression.

Background Understanding the natural history of abnormal spirometric patterns at different stages of life is critical to identify and optimise preventive strategies. We aimed to describe characteristics and risk factors of restrictive and obstructive spirometric patterns occurring before 40 years (young onset) and between 40 and 61 years (mid-adult onset). Methods We used data from the population-based cohort of the European Community Respiratory Health Survey (ECRHS). Prebronchodilator forced expiratory volume in one second (FEV 1 ) and forced vital capacity (FVC) were assessed longitudinally at baseline (ECRHS1, 1993–1994) and again 20 years later (ECRHS3, 2010–2013). Spirometry patterns were defined as: restrictive if FEV 1 /FVC≥LLN and FVC<10th percentile, obstructive if FEV 1 /FVC<LLN or normal otherwise. Five spirometry patterns were derived depending on whether participants never developed restrictive/obstructive (normal), developed restrictive/obstructive at baseline (young onset) or at last follow-up (mid-adult onset). The characteristics and risk factors associated with these patterns were described and assessed using multilevel multinomial logistic regression analysis adjusting for age, sex, sample (random or symptomatic) and centre. Results Among 3502 participants (mean age=30.4 (SD 5.4) at ECRHS1, 50.4 (SD 5.4) at ECRHS3), 2293 (65%) had a normal, 371 (11%) a young restrictive, 301 (9%) a young obstructive, 187 (5%) a mid-adult onset restrictive and 350 (10%) a mid-adult onset obstructive spirometric pattern. Being lean/underweight in childhood and young adult life was associated with the occurrence of the young spirometric restrictive pattern (relative risk ratio (RRR)=1.61 95% CI=1.21 to 2.14, and RRR=2.43 95% CI=1.80 to 3.29; respectively), so were respiratory infections before 5 years (RRR=1.48, 95% CI=1.05 to 2.08). The main determinants for young obstructive, mid-adult restrictive and mid-adult obstructive patterns were asthma, obesity and smoking, respectively. Conclusion Spirometric patterns with onset in young and mid-adult life were associated with distinct characteristics and risk factors.

Introduction/Background The prognosis of patients with platinum-resistant Epithelial Ovarian Cancer (EOC) remains poor, with few therapeutic choices available, mainly based on non-platinum compounds. This study aims at exploring whether platinum rechallenge may be an option for those patients who experience a platinum-resistant relapse after first line chemotherapy. Methodology In this retrospective, single-institute, observational study we enrolled all BRCA1/2 wild type (wt) patients who underwent primary cytoreductive surgery for EOC, between January 2017 and July 2021 and relapsed within 6 months after completing first line platinum-based chemotherapy, regardless of maintenance treatment. Patients receiving platinum monotherapy (P) where compared with those receiving pegylated liposomal doxorubicin (PLD), the most used schedule, or non-platinum/non-PLD therapy (paclitaxel or gemcitabine or topotecan, PGT). • Download figure • Open in new tab • Download powerpoint Abstract #620 Figure 1 PFS, Figure 2 OS Results Overall, 87 patients were identified, of which 18 (21%) received P, 50 (57%) underwent PLD and 19 (22%) had PGT. Platinum-based arm had a median progression-free survival of 9 months, compared with 4 and 6 months, in PLD and PGT respectively (log rank p = 0.002; P vs PLDp < 0.001; P vs PGT p = 0.047) (figure 1). With regard of Overall Survival (OS), patients receiving P achieved a 30-month median OS, compared with 15 and 17 months of PLD and PGT, respectively (log rank p = 0.20; P vs PLD p = 0.067; P vs PGT p = 0.26) (figure 2). Conclusion Platinum monotherapy is still an option in BRCAWt patients recurring within 6 months from first line treatment, with interesting survival results, compared to standard non-platinum monotherapy, commonly preferred and new targeted drugs. Disclosures none

We once again thank all the authors to this latest issue of “Editorial Compilations” for their original and comprehensive contributions, and we hope our readership enjoys this latest instalment in this series.