Role of nonneoplastic PVT in the natural history of patients with cirrhosis and first diagnosis of HCC.

BACKGROUND AND AIMS: HCC can increase the risk of nonneoplastic PVT in cirrhosis. However, the natural history of PVT and its prognostic role in HCC patients are unknown. APPROACH AND RESULTS: Consecutive HCC patients with cirrhosis undergoing laparoscopic ablation were retrospectively evaluated and followed up to 36 months. HCC and PVT characteristics and evolution were reviewed. PVT was categorized according to lumen occupancy (≤50%, >50% <100%, and = 100%) and extension to other veins. The evolution of thrombosis was considered at 1 year from diagnosis. Variables associated with the presence of PVT and evolution patterns were analyzed, as well as their impact on survival. In all, 750 patients were included, 88 of whom had PVT. On multivariate analysis, the occurrence of PVT at HCC diagnosis was associated with pretreatment total tumor volume ( p < 0.001) and clinically significant portal hypertension ( p = 0.005). During the follow-up, 46 de novo PVT occurred, 27/46 (58.7%) in the presence of a viable tumor. Among 115 PVT diagnosed in the presence of HCC, 83 had available radiological follow-up, and 22 were anticoagulated. The "complete/progressive" evolution pattern was associated with nonresponse to HCC treatment in non-anticoagulated patients. The presence of PVT was independently associated with lower overall survival, particularly when progressive or occlusive ( p < 0.001). A higher competing risk of death emerged for "complete and progressive" PVT, both for HCC-related ( p < 0.001) and non-HCC-related ( p = 0.002) death. CONCLUSIONS: HCC represents an independent risk factor for the occurrence and progression of PVT in cirrhosis. Since progressive and occlusive PVT seems to be an independent factor associated with mortality, screening and prompt treatment of this complication should be considered.

Evolution of Liver Transplantation Indications: Expanding Horizons.

Liver transplantation (LT) has significantly transformed the prognosis of patients with end-stage liver disease and hepatocellular carcinoma (HCC). The traditional epidemiology of liver diseases has undergone a remarkable shift in indications for LT, marked by a decline in viral hepatitis and an increase in metabolic dysfunction-associated steatotic liver disease (MASLD), along with expanded indications for HCC. Recent advancements in surgical techniques, organ preservation and post-transplant patients' management have opened new possibilities for LT. Conditions that were historically considered absolute contraindications have emerged as potential new indications, demonstrating promising results in terms of patient survival. While these expanding indications provide newfound hope, the ethical dilemma of organ scarcity persists. Addressing this requires careful consideration and international collaboration to ensure equitable access to LT. Multidisciplinary approaches and ongoing research efforts are crucial to navigate the evolving landscape of LT. This review aims to offer a current overview of the primary emerging indications for LT, focusing on acute-on-chronic liver failure (ACLF), acute alcoholic hepatitis (AH), intrahepatic and perihilar cholangiocarcinoma (i- and p-CCA), colorectal liver metastasis (CRLM), and neuroendocrine tumor (NET) liver metastases.

The proteomic landscape of renal tumors.

INTRODUCTION: Renal cell carcinoma (RCC) is the most fatal of the common urologic cancers, with approximately 35% of patients dying within 5 years following diagnosis. Therefore, there is a need for non-invasive markers that are capable of detecting and determining the severity of small renal masses at an early stage in order to tailor treatment and follow-up. Proteomic studies have proved to be very useful in the study of tumors. Areas covered: In this review, we will detail the current knowledge obtained by the different proteomic approaches, focusing on MS-based strategies, used to investigate RCC biology in order to identify diagnostic, prognostic and predictive biomarkers on tissue, cultured cells and biological fluids. Expert commentary: Currently, no reliable biomarkers or targets for RCC have been translated into the clinical setting. Moreover, despite the efforts of proteomics and other -omics disciplines, only a small number of them have been observed as shared targets between the different analytical platforms and biological specimens. The difficulty to define a specific molecular pattern for RCC and its subtypes highlights a peculiar profile and a heterogeneity that must be taken into account in future studies.

Second-harmonic generation imaging of semiconductor nanowires with focused vector beams.

We use second-harmonic generation (SHG) with focused vector beams to investigate individual vertically aligned GaAs nanowires. Our results provide direct evidence that SHG from oriented nanowires is mainly driven by the longitudinal field along the nanowire growth axis. Consequently, focused radial polarization provides a superior tool to characterize such nanowires compared to linear polarization, also allowing this possibility in the native growth environment. We model our experiments by describing the SHG process for zinc-blende structure and dipolar bulk nonlinearity.

Tumor size, stage and grade alterations of urinary peptidome in RCC.

BACKGROUND: Several promising biomarkers have been found for RCC, but none of them has been used in clinical practice for predicting tumour progression. The most widely used features for predicting tumour aggressiveness still remain the cancer stage, size and grade. Therefore, the aim of our study is to investigate the urinary peptidome to search and identify peptides whose concentrations in urine are linked to tumour growth measure and clinical data. METHODS: A proteomic approach applied to ccRCC urinary peptidome (n = 117) based on prefractionation with activated magnetic beads followed by MALDI-TOF profiling was used. A systematic correlation study was performed on urinary peptide profiles obtained from MS analysis. Peptide identity was obtained by LC-ESI-MS/MS. RESULTS: Fifteen, twenty-six and five peptides showed a statistically significant alteration of their urinary concentration according to tumour size, pT and grade, respectively. Furthermore, 15 and 9 signals were observed to have urinary levels statistically modified in patients at different pT or grade values, even at very early stages. Among them, C1RL, A1AGx, ZAG2G, PGBM, MMP23, GP162, ADA19, G3P, RSPH3, DREB, NOTC2 SAFB2 and CC168 were identified. CONCLUSIONS: We identified several peptides whose urinary abundance varied according to tumour size, stage and grade. Among them, several play a possible role in tumorigenesis, progression and aggressiveness. These results could be a useful starting point for future studies aimed at verifying their possible use in the managements of RCC patients.

Yersinia enterocolitica provides the link between thyroid-stimulating antibodies and their germline counterparts in Graves' disease.

Graves' disease results from thyroid-stimulating Abs (TSAbs) activating the thyrotropin receptor (TSHR). How TSAbs arise from early precursor B cells has not been established. Genetic and environmental factors may contribute to pathogenesis, including the bacterium Yersinia enterocolitica. We developed two pathogenic monoclonal TSAbs from a single experimental mouse undergoing Graves' disease, which shared the same H and L chain germline gene rearrangements and then diversified by numerous somatic hypermutations. To address the Ag specificity of the shared germline precursor of the monoclonal TSAbs, we prepared rFab germline, which showed negligible binding to TSHR, indicating importance of somatic hypermutation in acquiring TSAb activity. Using rFab chimeras, we demonstrate the dominant role of the H chain V region in TSHR recognition. The role of microbial Ags was tested with Y. enterocolitica proteins. The monoclonal TSAbs recognize 37-kDa envelope proteins, also recognized by rFab germline. MALDI-TOF identified the proteins as outer membrane porin (Omp) A and OmpC. Using recombinant OmpA, OmpC, and related OmpF, we demonstrate cross-reactivity of monoclonal TSAbs with the heterogeneous porins. Importantly, rFab germline binds recombinant OmpA, OmpC, and OmpF confirming reactivity with Y. enterocolitica. A human monoclonal TSAb, M22 with similar properties to murine TSAbs, also binds recombinant porins, showing cross-reactivity of a spontaneously arising pathogenic Ab with Y. enterocolitica. The data provide a mechanistic framework for molecular mimicry in Graves' disease, where early precursor B cells are expanded by Y. enterocolitica porins to undergo somatic hypermutation to acquire a cross-reactive pathogenic response to TSHR.

Lower urinary tract symptoms associated with neurological conditions: Observations on a clinical sample of outpatients neurorehabilitation service.

OBJECTIVES: The overall aims of this study were to investigate the lower urinary tract symptoms (LUTS) associated with neurological conditions and their prevalence and impact on a clinical sample of outpatients of a neurorehabilitation service. MATERIALS AND METHODS: We reviewed the files of 132 patients treated in our neurorehabilitation service from December 2012 to December 2013. Patients were divided into several subgroups based on the neurological diagnosis: Multiple Sclerosis (MS), other demyelinating diseases, Peripheral Neuropathy, neurovascular disorders (ND), neoplastic disease, traumatic brain injury (TBI), Parkinson and Parkinsonism, spinal cord injuries (SCI). Urinary status was based on medical evaluations of history of LUTS, type, degree, onset and duration of symptoms. We tried to analyze prevalence, kind of disorder, timing of presentation (if before or after the neurological onset) and eventual persistence of urological disorders (in the main group and in all subgroups). RESULTS: At the time of admission to our rehabilitation service, LUTS were observed in 14 out of 132 cases (11%). A high proportion of these outpatients (64.2%) presented bothersome urinary symptoms such as incontinence, frequency and urgency (storage LUTS). The most frequent symptom was urinary urge incontinence (42.8%). This symptom was found to be prevalent in the multiple sclerosis and neurovascular disorders. In 93% the urinary symptoms arose as a result of neurologic conditions and 78.5% did not present a complete recovery of urological symptoms in spite of improved self-reported functional activity limitations. None of these patients performed urological rehabilitation. CONCLUSIONS: Neurological disorders are a significant issue in rehabilitation services and it can lead to lower tract dysfunction, which causes LUTS. Storage symptoms are more common, especially urge incontinence. Current literature reports that a further optimization of the rehabilitation potential of neurologically ill patients is possible through an implementation of urological basic measures into the neurological treatment routine.

MALDI imaging mass spectrometry in glomerulonephritis: feasibility study.

AIMS: The in-situ proteomics technology known as matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) is a powerful technique that combines traditional histology and proteomics. METHODS AND RESULTS: MALDI-IMS was applied to routine diagnostic kidney biopsies in a small group of cases of membranous glomerulonephritis and minimal change disease. Molecular changes were observed not only in the tissue areas with pathological alterations, but also in morphologically normal-looking tissue, highlighting the potential feasibility of using MALDI-IMS as a tool in nephropathology. CONCLUSIONS: This technology can be applied to any biopsy where a frozen section is obtained as part of the diagnostic process. Although we do not yet know the molecular identity of the differentially expressed proteins/peptides, they could represent powerful classifiers of nosological groups.

Efficacy of spermatic vein ligation in patients affected by high grade left varicocele.

PURPOSE: To study the effect of high grade varicocele treatment in infertile patients. MATERIALS AND METHODS: Seventy-five patients were selected by the following criteria: infertility persisting for more than 1 year; abnormal semen parameters; no other infertility-related disease; no obvious causes of infertility in the subject's partner; basal eco-color Doppler ultrasound demonstrating continuous reflux in the spermatic vein. All patients considered for the study had at least a six months period from the diagnosis to the surgery due to waiting list, choice of the patient or time needed to complete diagnostic evaluation of the couple. The surgical procedure was performed through an inguinal approach. All enrolled patients were counseled to have unprotected intercourse during the ovulation period in order to maximize the probability of pregnancy within the 6-month preoperative period. The achievement of pregnancy and semen parameters were recorded during the preoperative and postoperative period. RESULTS: Two of the seventy-five patients were excluded because of persistent varicocele after surgery. The preoperative pregnancy rate was 1.3% (1 couple). The postoperative pregnancy rate was 42.5%. The stratification of pregnancies by semester showed a significantly higher rate in the first postoperative period (p = 0.0012). Mean time to conception was 13.5 months. Mean preoperative sperm count was 17.6x10(6)/mL compared to 19.7x10(6)/mL in the postoperative period (p < 0.0001). Mean percentage of progressive sperm motility was 13.7%, compared to 17.6% in the postoperative period (p < 0.0001). Mean percentage of normal sperm morphology was 7.6%, compared to 15.2% postoperatively (p < 0.0001). CONCLUSION: Surgical treatment of high grade varicocele proved to effectively treat associa¬ted infertility by improving seminal parameters and pregnancy rate in our patient cohort.

Inguinal polypropylene plug: a cause of unusual testicular tumor pelvic metastasis.

We report the case of a patient who had undergone polypropylene plug placement 3 years before and referred to our institution with testicular tumor. CT scan demonstrated an enlargement of pelvic lymph nodes on the tumor side while retroperitoneal nodes were normal. Orchifunicolectomy was performed and histopathological examination showed a mixed germ cell tumor involving the tunica vaginalis, rete testis, epididymis and spermatic cord. After surgery the patient was addressed to adjuvant chemotherapy according to PEB scheme. Clinical re-staging showed a decrease of the pelvic bulk disease whereas retroperitoneal nodes were still normal and tumor markers were negative. Left external, internal and common iliac lymphadenectomy as well as left modified template nervesparing retroperitoneal lymph node dissection was performed. Intraoperatively the node bulk was firmly adherent to the external iliac artery and extended until the common iliac bifurcation. In the deeper part of this enlarged and firm lymphatic chain the polypropylene plug placed at the time of hernioplasty was found. Behind the plug all retroperitoneal nodes appeared normal and resulted negative on histopathologic examination. The patient had an unusual metastatization, probably due to the plug.

Simultaneous management of renal carcinoma with caval vein thrombosis and double coronary artery disease.

INTRODUCTION: Recent advances in surgical and anesthesiology techniques allow simultaneous thoracic and abdominal operations to be performed for severe heart disease and benignant or malignant abdominal diseases. CASE REPORT: The simultaneous surgical management in a 75-year-old patient suffering from severe double coronary artery disease and a renal cell carcinoma with extended intravascular growth into the inferior vena cava is reported. CONCLUSION: The postoperative course was uneventful. Simultaneous surgery proved to be beneficial and safe, showing optimal results in our patient.

Effectiveness and safety of spinal anesthesia in patients undergoing open radical retropubic prostatectomy.

OBJECTIVE: Prostate cancer is one of the most widespread neoplasms affecting the male gender. The most commonly used procedures in various urological centers are laparoscopic and robotic surgery because they are considered minimally invasive techniques. We present our experience in traditional open radical prostatectomy performed under spinal anesthesia. MATERIALS AND METHODS: We reviewed the clinical courses of 88 consecutive patients who underwent open radical prostatectomy performed under spinal anesthesia at our Institution. RESULTS: Median age: 67.7 years. Median follow up duration: 48 months. Median pre-operative PSA: 15,9 ng/ml, median Prostate weight: 44.5 gr, median surgical time: 96.5 minutes (range 55-138). Perioperative complications were recorded. The most frequent complication was anemia, 9 cases need blood transfusion after surgery. Complications directly related to spinal anesthesia were not observed. Most patients were discharged within 5 days from the procedure. After two weeks we observed a quick recovery of total continence in 90% of patients. After 6 months all patients were perfectly continent. Erectile dysfunction after 6 months was reported by 48 patients. CONCLUSIONS: The reasons why the gold standard of radical prostatectomy surgery has been considered general anesthesia are essentially two: the long duration of the surgical procedure and the associated significant blood loss. Multiple evidences show that radical retropubic prostatectomy can be safely performed under spinal anaesthesia with various advantages. It is therefore no longer justified to consider general anesthesia as the gold standard for radical prostatectomy with an open technique.

Advances and Controversies in Acute Alcohol-Related Hepatitis: From Medical Therapy to Liver Transplantation.

Alcohol-related hepatitis (AH) is a clinical syndrome characterized by recent-onset jaundice in the context of alcohol consumption. In patients with severe AH "unresponsive" to steroid therapy, mortality rates exceed 70% within six months. According to European and American guidelines, liver transplantation (LT) may be considered in highly selected patients who do not respond to medical therapy. The aim of this narrative review is to summarize current knowledge from medical therapy to liver transplantation in acute alcohol-related hepatitis. Due to the impossibility to guarantee six-month abstinence, LT for AH is controversial. Principal concerns are related to organ scarcity in the subset of stigma of "alcohol use disorder" (AUD) and the risk of relapse to alcohol use after LT. Return to alcohol use after LT is a complex issue that cannot be assessed as a yes/no variable with heterogeneous results among studies. In conclusion, present data indicate that well-selected patients have excellent outcomes, with survival rates of up to 100% at 24 and 36 months after LT. Behavioral therapy, ongoing psychological support, and strong family support seem essential to improve long-term outcomes after LT and reduce the risk in relapse of alcohol use.

Liver transplantation for non-alcoholic fatty liver disease: indications and post-transplant management.

Non-alcoholic fatty liver disease (NAFLD) is currently the fastest growing indication to liver transplantation (LT) in Western Countries, both for end stage liver disease and hepatocellular carcinoma. NAFLD/non-alcoholic steatohepatitis (NASH) is often expression of a systemic metabolic syndrome; therefore, NAFLD/NASH patients require a multidisciplinary approach for a proper pre-surgical evaluation, which is important to achieve a post-transplant outcome comparable to that of other indications to LT. NAFLD/NASH patients are also at higher risk of post-transplant cardiovascular events, diabetes, dyslipidemia, obesity, renal impairment and recurrent NASH. Lifestyle modifications, included diet and physical activity, are key to improve survival and quality of life after transplantation. A tailored immunosuppressive regimen may be proposed in selected patients. Development of new drugs for the treatment of recurrent NASH is awaited.

Erectile properties of the Rho-kinase inhibitor SAR407899 in diabetic animals and human isolated corpora cavernosa.

BACKGROUND: RhoA-Rho kinase complex contributes to keep the cavernosus smooth muscle contracted and its inhibition is considered a potential strategy for the therapy of erectile dysfunction (ED). METHODS: We compared the effects of SAR407899, the Rho-kinase inhibitor Y-27632 and the PDE5 inhibitor sildenafil for their ability to relax corpus cavernosum strips contracted with phenylephrine in healthy and diabetic animals. Strips were obtained from WKY, spontaneous hypertensive (SHR), control CD, and diabetic CD rats, humans, control and diabetic rabbits. Diabetes was induced by streptozotocin or alloxan injection. In vivo penile erection (length) induced by drugs was measured in conscious rabbits. RESULTS: SAR407899 dose-dependently relaxed the pre-contracted corpora cavernosa in all species, with similar potency and efficacy in healthy vs diabetic rats, WKY vs SHR rats, healthy vs diabetic rabbits (IC(50) range from 0.05 to 0.29 µM, Emax range 89 to 97%). In the presence of the NO-synthase (NOS) inhibitor, L-NAME, the SAR407899 response did not decrease in any of the species or experimental conditions. The effect was confirmed in human strips where sildenafil was significantly less potent and effective, with IC50 respectively 0.13 and 0.51 µM; Emax 92 and 43%. Unlike SAR407899, the potency and efficacy of sildenafil and Y27632 were significantly reduced by diabetes and L-NAME. In vivo, SAR407899 dose-dependently induced rabbit penile erection, with greater potency and longer duration of action than sildenafil. Sildenafil, but not SAR407899, was less effective in alloxan-induced diabetes. CONCLUSION: The induction of penile erection by SAR407899, unlike that by sildenafil, is largely independent of e-NO activity. This suggests its use in erectile dysfunction for diabetic and hypertensive patients where e-NO activity is impaired.

The role of bladder neck preservation during radical prostatectomy: clinical and urodynamic study.

AIMS: Bladder neck preservation has caused an increase in urinary continence following radical prostatectomy, and has given rise to much controversy. We have reviewed our clinical and urodynamic experience collected since 1995 in patients subjected to radical prostatectomy with bladder neck preservation. MATERIALS AND METHODS: 180 patients were followed postoperatively using a pad test, an incontinence questionnaire and PSA dosage. In 66 early continent patients, test of maximum urethral closing pressure, functional length and active urethral continence were carried out, together with Valsalva leak point pressure tests and a pressure/flow study. The obtained data were then analysed. RESULTS: Urinary continence was achieved in 132/180 men (73%) already two weeks after operation. Three months, six months and one year later the continence rate was 89%, 95.5% and 97.7% (176/180) respectively. As far as the urodynamic parameters of the 66 patients fully tested are concerned, all showed high results. The active urethral continence capacity exceeded 200 cm/water, and the Valsalva leak point pressure equalled or exceeded 150 cm/water. CONCLUSIONS: Following an accurate dissection of the distal urethra, bladder neck preservation guarantees early recovery of continence, as confirmed by local urodynamic figures, and restores functional integration of both the urethral sphincteric-smooth proximal and distal striated units.

Compression Behavior of EBM Printed Auxetic Chiral Structures.

In this study, the cyclic compression and crush behavior of chiral auxetic lattice structures produced from titanium alloy (Ti6Al4V) metallic powder using electron beam melting (EBM) additive manufacturing technology is investigated numerically and experimentally. For material characterization and understanding the material behavior of EBM printed parts, tensile and three-point flexural tests were conducted. Log signals produced during the EBM process were investigated to confirm the stability of process and the health of the produced parts. Furthermore, a compressive cyclic load profile was applied to the EBM printed chiral units having two different thicknesses to track their Poisson's ratios and displacement limits under large displacements in the absence of degradation, permanent deformations and failures. Chiral units were also crushed to investigate the effect of failure and deformation mechanisms on the energy absorption characteristics. Moreover, a surface roughness study was conducted due to high surface roughness of EBM printed parts, and an equation is offered to define load-carrying effective areas to prevent misleading cross-section measurements. In compliance with the equation and tensile test results, a constitutive equation was formed and used after a selection and calibration process to verify the numerical model for optimum topology design and mechanical performance forecasting using a non-linear computational model with failure analysis. As a result, the cyclic compression and crush numerical analyses of EBM printed Ti6Al4V chiral cells were validated with the experimental results. It was shown that the constitutive equation of EBM printed as-built parts was extracted accurately considering the build orientation and surface roughness profile. Besides, the cyclic compressive and crush behavior of chiral units were investigated. The regions of the chiral units prone to prematurely fail under crush loads were determined, and deformation modes were investigated to increase the energy absorption abilities.

Glycaemic Control Achieves Sustained Increases of Circulating Endothelial Progenitor Cells in Patients Hospitalized for Decompensated Diabetes: An Observational Study.

BACKGROUND AND AIM: Diabetes reduces the levels of circulating endothelial progenitor cells (EPCs), which contribute to vascular homeostasis. In turn, low EPCs levels predict progression of chronic complications. Several studies have shown that hyperglycaemia exerts detrimental effects on EPCs. Improvement in glucose control with glucose-lowering medications is associated with an increase of EPCs, but only after a long time of good glycaemic control. In the present study, we examined the effect of a rapid glycaemic amelioration on EPC levels in subjects hospitalized for decompensated diabetes. METHODS: We used flow cytometry to quantify EPCs (CD34+/CD133+KDR+) in patients hospitalized for/with decompensated diabetes at admission, at discharge, and 2 months after the discharge. During hospitalization, all patients received intensive insulin therapy. RESULTS: Thirty-nine patients with type 1 or type 2 diabetes were enrolled. Average (± SEM) fasting glucose decreased from 409.2 ± 25.9 mg/dl at admission to 190.4 ± 12.0 mg/dl at discharge and to 169.0 ± 10.3 at 2 months (both p < 0.001). EPCs (per million blood cells) significantly increased from hospital admission (13.1 ± 1.4) to discharge (16.4 ± 1.1; p = 0.022) and remained stable after 2 months (15.5 ± 1.7; p = 0.023 versus baseline). EPCs increased significantly more in participants with newly-diagnosed diabetes than in those with pre-existing diabetes. The increase in EPCs was significant in type 1 but not in type 2 diabetes and in those without chronic complications. CONCLUSION: In individuals hospitalized for decompensated diabetes, insulin therapy rapidly increases EPC levels for up to 2 months. EPC defect, reflecting impaired vascular repair capacity, may be reversible in the early diabetes stages.

In Situ Monitoring of Powder Bed Fusion Homogeneity in Electron Beam Melting.

Increasing attention has been devoted in recent years to in situ sensing and monitoring of the electron beam melting process, ranging from seminal methods based on infrared imaging to novel methods based on backscattered electron detection. However, the range of available in situ monitoring capabilities and solutions is still quite limited compared to the wide number of studies and industrial toolkits in laser-based additive manufacturing processes. Some methods that are already industrially available in laser powder bed fusion systems, such as in situ detection of recoating errors, have not yet been investigated and tested in electron beam melting. Motivated by the attempt to fill this gap, we present a novel in situ monitoring methodology that can be easily implemented in industrial electron beam melting machines. The method is aimed at identifying local inhomogeneity and irregularities in the powder bed by means of layerwise image acquisition and processing, with no external illumination source apart from the light emitted by the hot material underneath the currently recoated layer. The results show that the proposed approach is suitable to detect powder bed anomalies, while also highlighting the link between the severity of in situ detected errors and the severity of resulting defects in the additively manufactured part.