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Sarcopenia and frailty are common complications in patients with cirrhosis evaluated for liver transplantation (LT). Although the negative impact of sarcopenia on patient's outcome has been well studied, the prognostic role of frailty is not as clear. We assessed the prevalence of sarcopenia and frailty and the clinical impact of frailty in a prospective cohort of cirrhosis patients with and without hepatocellular carcinoma (HCC) listed for LT. Patients with cirrhosis were prospectively recruited at the time of admission into the waiting list. Clinical and lab values were collected. Physical frailty was assessed by liver frailty index (LFI) and patients were categorized into robust (< 3.2); pre-frail (between 3.2 and 4.5), and frail (> 4.5). Skeletal muscle mass was evaluated via skeletal muscle index (SMI) obtained from last CT scan before LT; sarcopenia was defined by SMI < 50 cm2/m2 in males and < 39 cm2/m2 in females. 105 patients were included, of which 42 (40%) had hepatocellular carcinoma (HCC). In patients without HCC (63.5% males, median age 61 years), 36.5% were frail, 50.8% were pre-frail and 12.7% were robust. Frail patients were older than non-frail patients (63 vs. 56; p = 0.008) and had more severe liver disease (Child C: 65% vs. 37.5%; p = 0.02). Prevalence of sarcopenia in patients without HCC was 63%, with similar value of median SMI between frail and not frail patients (p = 0.454). Patients with HCC (78.6% males, 65 years old) were 21.4% frail, 61.9% pre-frail, and 16.7% robust. Frail patients had more severe liver disease (Child C: 77% vs. 18.2%; p = 0.004), whereas age was comparable to non-frail patients; among patients without HCC, during a median follow-up of 263 days, 17% died (of which 72% were frail) and 10 patients were delisted due to clinical improvement (none of whom were frail). Among those with HCC, during a median follow-up of 289 days, 4 (9%) patients died of which 50% were frail. Frailty and sarcopenia are common complications in patients with cirrhosis awaiting LT. Frailty appears to be associated with an increased risk of mortality during wait-list time especially in those with decompensated cirrhosis. At univariate analysis Meld score, Child score and presence of frailty were found to be associated with shorter survival, however, at multivariate analysis presence of frailty and Child C vs. A/B were the only independent predictor of death. Larger cohorts are required to confirm these results. [ABSTRACT FROM AUTHOR]

Bacterial infections are a common complication in patients with decompensated liver cirrhosis. The complex landscape of cirrhosis, characterized by immune paralysis and an exhausted response to exogenous triggers, explains the higher prevalence of such infections, particularly in advanced disease stages. In clinical practice, the onset of a bacterial infection can lead to further deterioration of hepatic and extra-hepatic function, potentially resulting in acute decompensation or acute-on-chronic liver failure. This has significant clinical implications, particularly for patients awaiting a transplant. In this review, we will discuss the latest evidence on the diagnosis and therapy of bacterial infections in patients with decompensated cirrhosis. Additionally, we will analyze the impact of bacterial infections in the context of liver transplantation, discussing debated topics such as the timing of transplantation in patients with infections, potential implications for prioritization, effects on post-operative recovery, grafts, and patient survival. [ABSTRACT FROM AUTHOR]

Background: Extracellular vesicles (EVs) modulate inflammation, coagulation and vascular homeostasis in decompensated cirrhosis. Aim: To characterize the profile of plasmatic EVs in patients with decompensated cirrhosis and bacterial infections and evaluate the association between EVs and the development of hemostatic complications. Methods: We measured the levels of EVs using high-sensitivity flow cytometry and phospholipid-dependent clotting time (PPL) in a prospective cohort of hospitalized patients with acutely decompensated cirrhosis with versus without bacterial infections. A separate cohort of patients with bacterial infections without cirrhosis was also enrolled. We measured endothelium-, tissue factor (TF)-bearing, platelet- and leukocyte-derived EVs. In patients with infections, EVs were reassessed upon resolution of infection. Bleeding and thrombotic complications were recorded during 1-year follow-up. Results: Eighty patients with decompensated cirrhosis were recruited (40 each with and without bacterial infections). Electron microscopy confirmed the presence of plasma EVs. Despite no difference in total EVs and PPL, patients with cirrhosis and infection had significantly higher TF+ EVs, P-Selectin+ EVs (activated platelet-derived), CD14+ EVs (monocyte/macrophages derived) and CD14+ TF+ EVs versus those with cirrhosis without infection. Upon infection resolution, levels of these EVs returned to those without infection. Patients with infections showed a significant association between reduced P-Selectin+ EVs and bleeding complications (HR 8.0 [95%CI 1.3-48.1]), whereas high levels of leukocyte-derived EVs (CD45+) and CD14+ EVs were significantly associated with thrombotic complications (HR 16.4 [95%CI 1.7-160] and 10.9 [95%CI 1.13-106], respectively). Results were confirmed in a validation cohort. Conclusion: Bacterial infections are associated with particular alterations of plasma EVs profile in decompensated cirrhosis. Bacterial infections trigger the release of EVs originating from various cell types, which may tip the precarious hemostatic balance of patients with acutely decompensated cirrhosis towards hyper- or hypocoagulability. [ABSTRACT FROM AUTHOR]

Simple Summary: Maize is one of the major crops of the world for feed, food, and industrial uses. It originated in Central America and was first introduced into Europe at the end of the 15th century. Due to its adaptability, farmers and breeders across Europe have developed a wide diversity of local maize varieties with different characteristics over the past centuries. Many of these are conserved in genebanks' seed collections, but little is known about their specific characteristics. Here, we present results obtained by the European Evaluation Network for Maize, a private–public partnership with partners from nine countries aimed at promoting the valorization of maize genetic resources in breeding programs. The work describes the selection and the genetic and phenotypic evaluation of a collection of 626 maize landraces preserved in European genebanks, providing evidence for historic introductions and geographic adaptation. In a world where climate change, rising food prices, and other issues are affecting food security and the environment, the conservation and use of crop diversity is becoming increasingly important. The results of our study will facilitate the use of maize genetic resources in breeding for resilience to climate change, for sustainable agriculture, food security, and food quality. The ECPGR European Evaluation Network (EVA) for Maize involves genebanks, research institutions, and private breeding companies from nine countries focusing on the valorization of maize genetic resources across Europe. This study describes a diverse collection of 626 local landraces and traditional varieties of maize (Zea mays L.) from nine European genebanks, including criteria for selection of the collection and its genetic and phenotypic diversity. High-throughput pool genotyping grouped the landraces into nine genetic groups with a threshold of 0.6 admixture, while 277 accessions were designated admixed and likely to have resulted from previous breeding activities. The grouping correlated well with the geographic origins of the collection, also reflecting the various pathways of introduction of maize to Europe. Phenotypic evaluations of 588 accessions for flowering time and plant architecture in multilocation trials over three years confirmed the great diversity within the collection, although phenotypic clusters only partially correlated with the genetic grouping. The EVA approach promotes conservation of genetic resources and opens an opportunity to increase genetic variability for developing improved varieties and populations for farmers, with better adaptation to specific environments and greater tolerance to various stresses. As such, the EVA maize collection provides valuable sources of diversity for facing climate change due to the varieties' local adaptation. [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: The prognostic performance of von Willebrand factor (VWF) may vary across clinical stages of advanced chronic liver disease (ACLD). Therefore, we investigated the evolution of VWF and other biomarkers throughout the full ACLD spectrum and evaluated their stage‐specific prognostic utility. Methods: We retrospectively included Viennese ACLD patients with available information on hepatic venous pressure gradient (HVPG), C‐reactive protein (CRP)/VWF levels and outcomes. ACLD stages were defined according to D'Amico et al. We included an external validation cohort from Padua. Results: We observed gradual increases in VWF throughout ACLD stages. In contrast, HVPG levelled off in decompensated ACLD (dACLD), whereas MELD showed only minor changes in the early stages and CRP did not increase until stage 3. VWF was associated with hepatic decompensation/liver‐related death in compensated ACLD (cACLD) in a fully adjusted model, while it was not independently predictive of ACLF/liver‐related death in dACLD. After backward selection, HVPG/CRP/VWF remained the main predictors of hepatic decompensation/liver‐related death in cACLD. Notably, the performance of the non‐invasive CRP/VWF‐based model was comparable to invasive HVPG‐based models (C‐index:0.765 ± 0.034 vs. 0.756 ± 0.040). The discriminative ability of the CRP/VWF‐based model was confirmed in an external validation cohort using another VWF assay which yielded systematically lower values. Conclusion: VWF is the only biomarker that gradually increases across all ACLD stages. It is of particular prognostic value in cACLD, where a CRP/VWF‐based model is equivalent to an invasive HVPG‐based model. Systematic differences in VWF underline the importance of interlaboratory surveys. Moreover, our findings reinforce the notion that, already in cACLD, inflammation is a key disease‐driving mechanism. [ABSTRACT FROM AUTHOR]

The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan–Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23–0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16–0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02–2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Modes of propagation through an optical system are generally defined as the eigensolutions of the wave equation in the system. When propagation occurs through complicated or highly scattering media, however, modes are better identified as the best orthogonal communication channels to send information between sets of input and output apertures. Here we determine the optimal bidirectional orthogonal communication channels through arbitrary and scattering optical systems using photonic processors. The processors consist of meshes of electrically tuneable Mach–Zehnder interferometers in silicon photonics. The meshes can configure themselves based on simple power maximization or minimization algorithms, without external calculations or calibration or any prior knowledge of the optical system. The identification of the communication mode channels corresponds to a singular value decomposition of the entire optical system, autonomously performed by the photonic processors. We observe crosstalk below –30 dB between the optimized channels even in the presence of distorting masks or partial obstructions. In these cases, although the beams bear little resemblance to conventional mode families, they still show orthogonality. These findings offer potential for applications in multimode optical communication systems, promising efficient channel identification, adaptability to dynamic media and robustness against environmental challenges. Self-configuring meshes of integrated Mach–Zehnder interferometers determine the optimal communication channels through unknown optical media, with the resulting modes showing crosstalk below –30 dB. [ABSTRACT FROM AUTHOR]

Background and Aims: The objective of this study was to assess the impact of the COVID-19 pandemic and direct-acting antiviral (DAA) agents on mortality related to chronic liver diseases (CLD). Methods: Age-standardized mortality rates were computed based on CLD as the underlying cause of death (UCOD) and as any mention in death certificates (multiple causes of death-MCOD). Time trends in age-standardized mortality rates were investigated using generalized estimation equation models. Additionally, we conducted age, period, and birth cohort (APC) analyses on CLD-related mortality associated with alcohol and hepatitis C virus (HCV). Results: Between 2008 and 2021, among residents in the Veneto region (Northeastern Italy) aged ≥35 years, there were 20 409 deaths based on the UCOD and 30 069 deaths based on MCOD from all CLD. We observed a 4% annual decline in age-standardized MCOD-based mortality throughout 2008--2021, with minor peaks corresponding to COVID-19 epidemic waves. Starting in 2016, the decline in HCV-related mortality accelerated further (p < .001). A peak in HCV-related mortality in the 1963--1967 birth cohort was observed, which levelled off by the end of the study period. Mortality related to alcoholic liver disease declined at a slower pace, becoming the most common aetiology mentioned in death certificates. Conclusions: The study demonstrates a significant decrease in HCV-related mortality at the population level in Italy with the introduction of DAAs. Continuous monitoring of MCOD data is warranted to determine if this favourable trend will continue. Further studies utilizing additional health records are needed to clarify the role of other CLD etiologies. [ABSTRACT FROM AUTHOR]

Programmable photonic circuits require an electronic control layer to configure and stabilize the optical functionality at run‐time. Such control action is normally implemented by supervising the status of the circuit with integrated light monitors and by providing feedback signals to integrated actuators. This paper demonstrates that the control action can be effectively performed with electrical signals that are time‐multiplexed directly on the photonic chip. To this aim, the necessary electronic functionalities are monolithically integrated in a conventional 220 nm silicon photonics platform with no changes to the standard fabrication process. By exploiting a non‐conventional structure to implement metal‐oxide–semiconductor field‐effect transistors, an electronic controller is co‐designed into a programmable photonic circuit to enable a time‐multiplexed readout of integrated photodetectors and sequential activation of thermal phase shifters with on‐chip electronic memory. The accuracy of the time‐multiplexed control, achieved on a time scale of less than 10 ms, is demonstrated by penalty‐free routing of 10 Gbit s−1 modulated signals. This approach can be straightforwardly applied to large‐scale photonic chips to reduce the number of required electrical input/output connections. [ABSTRACT FROM AUTHOR]

Background: Training programs on resuscitation have been developed using simulation-based learning to build skills, strengthen cognitive strategies, and improve team performance. This is especially important for residency programs where reduced working hours and high numbers of residents can reduce the educational opportunities during the residency, with lower exposure to practical procedures and prolonged length of training. Within this context, gamification has gained popularity in teaching and learning activities. This report describes the implementation of a competition format in the context of newborn resuscitation and participants' perceptions of the educational experience. Methods: Thirty-one teams of three Italian pediatric residents participated in a 3-day simulation competition on neonatal resuscitation. The event included an introductory lecture, familiarization time, and competition time in a tournament-like structure using high-fidelity simulation stations. Each match was evaluated by experts in neonatal resuscitation and followed by a debriefing. The scenarios and debriefings of simulation station #1 were live broadcasted in the central auditorium where teams not currently competing could observe. At the end of the event, participants received an online survey regarding their perceptions of the educational experience. Results: 81/93 (87%) participants completed the survey. Training before the event mostly included reviewing protocols and textbooks. Low-fidelity manikins were the most available simulation tools at the residency programs. Overall, the participants were satisfied with the event and appreciated the live broadcast of scenarios and debriefings in the auditorium. Most participants felt that the event improved their knowledge and self-confidence and stimulated them to be more involved in high-fidelity simulations. Suggested areas of improvement included more time for familiarization and improved communication between judges and participants during the debriefing. Conclusions: Participants appreciated the simulation competition. They self-perceived the educational impact of the event and felt that it improved their knowledge and self-confidence. Our findings suggest areas of improvements for further editions and may serve as an educational model for other institutions. [ABSTRACT FROM AUTHOR]

(1) Background: Little is known about the long-term impact of sustained virological response (SVR) on fibrosis progression and patient survival in liver transplantation (LT) recipients treated with direct-acting antivirals (DAAs). We investigated liver fibrosis evolution and patient survival in hepatitis C virus (HCV)-infected patients receiving DAAs after LT. (2) Methods: All consecutive HCV-infected patients treated with DAAs after LT between May 2014 and January 2019 were considered. The clinical and virological features were registered at the baseline and during the follow-up. The liver fibrosis was assessed by liver biopsy and/or transient elastography (TE) at the baseline and at least 1 year after the end of treatment (EoT). (3) Results: A total of 136 patients were included. The SVR12 was 78% after the first treatment and 96% after retreatment. After the SVR12, biochemical tests improved at the EoT and remained stable throughout the 3-year follow-up. Liver fibrosis improved after the SVR12 (p < 0.001); nearly half of the patients with advanced liver fibrosis experienced an improvement of an F ≤ 2. The factors associated with lower survival in SVR12 patients were the baseline platelet count (p = 0.04) and creatinine level (p = 0.04). (4) Conclusions: The long-term follow-up data demonstrated that SVR12 was associated with an improvement in hepatic function, liver fibrosis, and post-LT survival, regardless of the baseline liver fibrosis. The presence of portal hypertension before the DAAs has an impact on patient survival, even after SVR12. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) is a prevalent underlying disease, leading to liver transplantation (LT) for both decompensated cirrhosis and hepatocellular carcinoma (HCC). The hepatitis delta virus (HDV) affects approximately 5–10% of HBsAg carriers, accelerating the progression of liver injury and HCC. The initial introduction of HBV immunoglobulins (HBIG), and then of nucleos(t)ide analogues (NUCs), considerably improved the survival of HBV/HDV patients post-transplantation, as they helped prevent re-infection of the graft and recurrence of liver disease. Combination therapy with HBIG and NUCs is the primary post-transplant prophylaxis strategy in patients transplanted for HBV- and HDV-related liver disease. However, monotherapy with high-barrier NUCs, such as entecavir and tenofovir, is safe and also effective in some individuals who are at low risk of HBV reactivation. To address the problems of organ shortage, last-generation NUCs have facilitated the use of anti-HBc and HBsAg-positive grafts to meet the ever-increasing demand for grafts. [ABSTRACT FROM AUTHOR]

The objective of this study is to describe the clinical features of young infants with apneas as a clinical sign of COVID-19. We reported the cases of 4 infants who needed respiratory support in our PICU for a severe course of COVID-19 complicated with recurrent apneas. Moreover, we conducted a review of the literature about COVID-19 and apneas in infants ≤ 2 months of corrected age. A total of 17 young infants were included. Overall, in most of the cases (88%), apnea was an initial symptom of COVID-19, and in two cases, it recurred after 3–4 weeks. Regarding neurological workup, most children underwent a cranial ultrasound, while a minority underwent electroencephalography registration, neuroimaging, and lumbar punctures. One child showed signs of encephalopathy on electroencephalogram, with further neurological workup resulting normal. SARS-CoV-2 was never found in the cerebrospinal fluid. Ten children required intensive care unit admission, with five of them needing intubation and three non-invasive ventilation. A less invasive respiratory support was sufficient for the remaining children. Eight children were treated with caffeine. All patients had a complete recovery. Conclusion: Young infants with recurrent apneas during COVID-19 usually need respiratory support and undergo a wide clinical work-up. They usually show complete recovery even when admitted to the intensive care unit. Further studies are needed to better define diagnostic and therapeutic strategies for these patients. What is Known: • Although the course of COVID-19 in infants is usually mild, some of them may develop a more severe disease needing intensive care support. Apneas may be a clinical sign in COVID-19. What is New: • Infants with apneas during COVID-19 may require intensive care support, but they usually show a benign course of the disease and full recovery. [ABSTRACT FROM AUTHOR]

Patients with decompensated cirrhosis are at risk of portal vein thrombosis (PVT). We prospectively investigated whether alterations of platelet aggregation can predict PVT in decompensated cirrhosis. At baseline, all patients underwent whole‐blood aggregometry (Multiplate®) to assess ADP‐induced platelet aggregation. Aggregometry results were expressed as the ratio between platelet aggregation and platelet count (PLT ratio). Then, patients with cirrhosis were prospectively followed for 1 year for PVT development. One‐hundred and twenty‐eight patients with decompensated cirrhosis were included (Child‐Pugh A/B/C 12/39/49%). The cumulative incidence of PVT was 14%. On multivariate analysis, the PLT ratio (OR 4.5, 95% CI 2.63–7.67; p <.0001) and Child‐Pugh C versus A/B (OR 4.1, 95% CI 1.18–14.80; p =.03) were independently associated with PVT. The discriminative ability of the PLT ratio was higher than Child‐Pugh (AUC 0.92 vs 0.70, p <.0001). A PLT ratio > 0.75 had 83% sensitivity and 84% specificity for PVT. In conclusion, the PLT ratio by Multiplate® seems a promising thrombotic biomarker in decompensated cirrhosis. [ABSTRACT FROM AUTHOR]

Initial staging of prostate cancer (PCa) is usually performed with conventional imaging (CI), involving computed tomography (CT) and bone scanning (BS). The aim of this study was to analyze the role of [18F]F-choline positron emission tomography (PET)/CT in the initial management and outcome prediction of PCa patients by analyzing data from a multidisciplinary approach. We retrospectively analyzed 82 patients who were discussed by the uro-oncology board of the University Hospital of Ferrara for primary staging newly diagnosed PCa (median age 72 (56–86) years; median baseline prostate specific antigen (PSA) equal to 8.73 ng/mL). Patients were divided into three groups based on the imaging performed: group A = only CI; group B = CI + [18F]F-choline PET/CT; group C = only [18F]F-choline PET/CT. All data on imaging findings, therapy decisions and patient outcomes were retrieved from hospital information systems. Moreover, we performed a sub-analysis of semiquantitative parameters extracted from [18F]F-choline PET/CT to search any correlation with patient outcomes. The number of patients included in each group was 35, 35 and 12, respectively. Patients with higher values of initial PSA were subjected to CI + PET/CT (p = 0.005). Moreover, the use of [18F]F-choline PET/CT was more frequent in patients with higher Gleason score (GS) or ISUP grade (p = 0.013). The type of treatment performed (surgery n = 33; radiation therapy n = 22; surveillance n = 6; multimodality therapy n = 6; systemic therapy n = 13; not available n = 2) did not show any relationship with the modality adopted to stage the disease. [18F]F-choline PET/CT induced a change of planned therapy in 5/35 patients in group B (14.3%). Moreover, patients investigated with [18F]F-choline PET/CT alone demonstrated longer biochemical recurrence (BCR)-free survival (30.8 months) in comparison to patients of groups A and B (15.5 and 23.5 months, respectively, p = 0.006), probably due to a more accurate selection of primary treatment. Finally, total lesion choline kinase activity (TLCKA) of the primary lesion, calculated by multiplying metabolic tumor volume and mean standardized uptake value (SUVmean), was able to more effectively discriminate patients who had recurrence after therapy compared to those without (p = 0.03). In our real-world experience [18F]F-choline PET/CT as a tool for the initial management of PCa had a relevant impact in terms of therapy selection and was associated with longer BCR-free survival. Moreover, TLCKA of the primary lesion looks a promising parameter for predicting recurrence after curative therapy. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is a known risk factor for postoperative morbidity and mortality in patients awaiting liver transplantation (LT). Malnutrition is a potentially reversible risk factor, though there are no clear guidelines on the best mechanism for an improvement. It also remains unclear if preoperative nutritional interventions have benefits to post‐transplant outcomes for transplant recipients. Objectives: Primary objective: To identify if preoperative optimization of nutritional status is associated with improved short‐term outcomes after LT. Secondary Objectives: To determine if preoperative improvement of malnutrition improves short‐term outcomes after LT, as well as if weight loss in obese patients affects short‐term outcomes after LT. Data sources: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. Methods: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. POSPERO Protocol ID: CRD42021237450 Results: 3851 records were identified in searching the databases, 3843 records were excluded by not fulfilling eligibility criteria. Seven full‐text articles were included for the final analysis of which three were randomized controlled trials, one was prospective observational studies, and three were retrospective observational studies. No appreciable difference in mortality, post‐transplant complication rate was noted across the studies. Length of stay (LOS) was noted to be shorter in two observational studies of Vitamin D deficiency in liver transplant patients. Conclusions: We have made a weak recommendation supporting pre‐transplant nutritional supplementation due to possible benefit in reducing LOS as well as the lack of harm (Quality of Evidence low | Grade of Recommendation; Weak). No effective conclusions were reached for the secondary objectives due to the conflicting evidence. [ABSTRACT FROM AUTHOR]

Maternity statistics of England in 2020 showed rise in Caesarean Section (CS) rate to 31%. Some studies correlated adverse gynaecological symptoms e.g. menstrual irregularities and pelvic pain to 'niche' formation at CS scar site. Niche formation was speculated to cause myometrial hypertrophy aggravating these symptoms. This was a prospective comparative histological study including 52 consecutive benign hysterectomy specimens which were categorised into 2 groups: (i) specimens with CS scar (n = 22), (ii) specimens with no CS scar (n = 30). Median (IQ range) uteri weight was 97.2grms (43.5–226) and 91.7grms (35.7–201.7) in study and control groups, respectively (p =.991). Mean (±SD) thickness of anterior myometrial wall was 18.7 mm (±3.6) and 19.4 mm (±4.5) in study and control groups, respectively (p =.58). Mean (±SD) thickness of posterior myometrial wall was 19.1 mm (±3.7) and 18.7 mm (±3.9) in study and control groups, respectively (p =.78). The assumption that CS scar causes myometrial hypertrophy was not demonstrated in this study. What is already known on this subject? Maternity statistics world-wide show a continuous rise in the rate of Caesarean Section (CS) operation. The CS scar is assumed to be related to adverse clinical gynaecological symptoms such as intermenstrual bleeding, dysmenorrhoea, dyspareunia and chronic pelvic pain; however, the mechanism of this association is not clear. Further, little is known about the effects of CS scar on uterine wall morphology and function. What do the results of this study add? This study was the first prospective series in the literature to compare the uteri with scar with those without in respect of weight and myometrial wall thickness. It was not able to demonstrate the association between having CS scar and myometrial hypertrophy which was hypothesised to be the cause of adverse gynaecological symptoms. However, the microscopic examination of the CS scar revealed adenomyosis, haemorrhage and/or chronic inflammation in most cases. What are the implications of these findings for clinical practice and/or future research? The clinical implication of the histological changes shown in the CS scar requires large comparative clinical studies. [ABSTRACT FROM AUTHOR]

Venous thrombosis is a frequent complication in cancer and is associated with high morbidity and mortality. Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer‐related death worldwide, and it is associated with preexisting cirrhosis in 90% of cases. Patients with cirrhosis acquire complex alterations in their haemostatic system that may predispose them to bleed or thrombotic complications. There is growing evidence that HCC may tilt the haemostatic equilibrium in cirrhosis towards hypercoagulability, thus increasing the risk of venous thrombosis. Previously described mechanisms of HCC‐driven thrombophilia include thrombocytosis and increased platelet activation/function, increased fibrinogen concentration/polymerization, enhanced thrombin generation, hypofibrinolysis, and release of tissue factor‐expressing microvesicles. Nevertheless, there are currently no specific guidelines on risk stratification and management of thromboprophylaxis in patients with cirrhosis and HCC. Our review endeavours to summarize the latest findings on epidemiology, risk factors and pathogenesis of non‐malignant venous thrombosis in patients with cirrhosis and HCC, and provide evidence in support of tailored management of thrombotic risk in these patients. [ABSTRACT FROM AUTHOR]

The study aimed to explore the use of diagnostics for febrile children presenting to European emergency departments (EDs), the determinants of inter-hospital variation, and the association between test use and hospitalization. We performed a secondary analysis of a cross-sectional observational study involving 28 paediatric EDs from 11 countries. A total of 4560 children < 16 years were included, with fever as reason for consultation. We excluded neonates and children with relevant comorbidities. Our primary outcome was the proportion of children receiving testing after primary evaluation, by country and by focus of infection. Variability between hospitals and effects of blood testing on patient disposition were explored by multilevel regression analyses, adjusting for patient characteristics (age group, triage level, appearance, fever duration, focus of infection) and hospital type (academic, teaching, other). The use of routine diagnostics varied widely, mostly in the use of blood tests, ranging from 3 to 75% overall across hospitals. Age < 3 months, high-acuity triage level, ill appearance, and suspicion of urinary tract infection displayed the strongest association with blood testing (odds ratios (OR) of 8.71 (95% CI 5.23–14.53), 19.46 (3.66–103.60), 3.13 (2.29–4.26), 10.84 (6.35–18.50), respectively). Blood testing remained highly variable across hospitals (median OR of the final model 2.36, 1.98–3.54). A positive association was observed between blood testing and hospitalization (OR 13.62, 9.00–20.61). Conclusion: the use of diagnostics for febrile children was highly variable across European EDs, yet patient and hospital characteristics could only partly explain inter-hospital variability. Focus groups of participating sites should help define reasons for unexpected variation. What is Known: • Although previous research has shown variation in the emergency department (ED) management of febrile children, there is limited information on the use of diagnostics in European EDs. • A deeper knowledge of variability and its determinants can steer optimization of care. What is New: • The use of diagnostics for febrile children was highly variable across European EDs, yet patient and hospital characteristics could only partly explain inter-hospital variability. • Data on between-centre comparison offer opportunities to further explore factors influencing unwarranted variation. [ABSTRACT FROM AUTHOR]

The letter to the editor discusses the use of whole blood platelet aggregation in patients with cirrhosis. The authors of the letter question the use of whole blood aggregometry in patients with thrombocytopenia and suggest that platelet volume may influence the results. However, the authors of the original study argue that the increased mean platelet volume (MPV) in patients with cirrhosis may be due to factors specific to HBV infection and not necessarily indicative of platelet aggregation. They also argue that the assessment of platelet aggregation should take into consideration the overall platelet response in an assay milieu that mimics in vivo conditions. The authors conclude that more data on MPV are needed before drawing any conclusions about its potential effect on platelet aggregation in cirrhosis. [Extracted from the article]

In patients with cirrhosis, particularly those with hepatocellular carcinoma (HCC), hypercoagulability may be associated with purported increased risks of portal vein thrombosis and cirrhosis progression. In this study, we extensively investigated hemostatic alterations potentially responsible for the thrombotic tendency in HCC, and evaluated whether such alterations were predictive of hepatic decompensation. Patients with cirrhosis at all stages were prospectively recruited and underwent an extensive hemostatic assessment, including all procoagulant factors and inhibitors, thrombin generation with and without thrombomodulin (TG), profibrinolytic and antifibrinolytic factors, and plasmin‐antiplasmin complex. In study part 1 (case control), we compared alterations of coagulation and fibrinolysis in patients with cirrhosis with versus without HCC. In study part 2 (prospective), the subgroup of patients with decompensated cirrhosis was followed for development of further decompensation, and predictors of outcome were assessed by multivariate analysis. One‐hundred patients were recruited (50 each with and without HCC). Severity of cirrhosis was comparable between groups. Median HCC volume was 9 cm3 (range: 5‐16). Compared with controls, patients with HCC demonstrated a significantly more prothrombotic hemostatic profile due to increased TG and reduced activation of fibrinolysis, independent of cirrhosis stage. During a median follow‐up of 175 days, 20 patients with decompensated cirrhosis developed further episodes of decompensation that were predicted by low FVII and high plasminogen activator inhibitor‐1 levels, independent of Model for End‐Stage Liver Disease score. Conclusion: Patients with cirrhosis with HCC have profound hyper‐coagulable changes that can account for their increased thrombotic tendency. In contrast, hypercoagulability in patients with decompensated cirrhosis is more likely a consequence of chronic liver disease rather than a driver for cirrhosis progression. [ABSTRACT FROM AUTHOR]

The noise power spectral density of a detector is essential for determining the frequency of operation and readout architecture that yields an optimal signal-to-noise ratio. In this work, we characterize a waveguide-integrated PbTe mid-infrared detector and report on its noise spectrum, highlighting the presence of a current-dependent 1/f term dominating at low frequency and/or high bias over the Johnson component typical of a photoconductor. This behaviour, together with the substantially flat frequency response in the range between 1 kHz to 1 MHz, guide towards a lock-in readout strategy, that allows one to operate in the region of minimum noise without penalties in the detection performance. Practical guidelines to optimize the readout resolution are provided and the limit of detection of a gas sensing system exploiting PbTe photoconductors is derived, as an example of how a careful co-design of sensors and electronics can dramatically improve the detection performance. [ABSTRACT FROM AUTHOR]

Background & Aims: Understanding factors responsible for the increased bleeding tendency in acute‐on‐chronic liver failure (ACLF) would improve the management of these complications. We investigated coagulation alterations in ACLF and assessed whether they were predictive of bleeding. Methods: Cirrhosis patients with ACLF (cases) and acute decompensation (AD, controls) were prospectively recruited and underwent an extensive haemostatic assessment including standard tests, pro and anticoagulant factors, thrombomodulin‐modified thrombin generation (TG) and thromboelastometry (ROTEM®). In study part 1 (case‐control), we compared coagulation in ACLF vs AD. In study part 2 (prospective), all patients were followed for bleeding, and predictors of outcome were assessed. Results: Ninety‐one patients were included (51 with ACLF, 40 with AD). Infections and ascites/renal dysfunction were the most common precipitating and decompensating events. Platelet count was lower while INR and activated partial thrombin time were longer in ACLF cohort vs AD. Regarding clotting factors, fibrinogen and factor VIII were comparable between groups while protein C and antithrombin were significantly reduced in ACLF. Endogenous thrombin potential by TG was comparable between groups. Clotting formation time and clot stability by ROTEM® were significantly lower in ACLF, indicative of a more hypocoagulable state. No haemostasis alteration could discriminate between patients who had bleeding complications during hospitalization and those who did not. Conclusion: We found coagulation changes in ACLF to largely overlap with that of AD and evidence of preserved coagulation capacity in both groups. ROTEM alterations were indicative of a more pronounced hypocoagulable state in ACLF; however, no correlation was found between such alterations and bleeding. [ABSTRACT FROM AUTHOR]

To overcome this concern, we adjusted platelet aggregation measurements to each subject's platelet count both in the peripheral and portal blood samples, by using the "platelet aggregation to platelet count ratio" (PLT-ratio: [AUC/platelet count x10 SP 3 sp ] x 1000) [[15]]. Keywords: Cirrhosis; platelet aggregability; platelet function analysis; portal hypertension; portal vein EN Cirrhosis platelet aggregability platelet function analysis portal hypertension portal vein 1104 1106 3 08/29/22 20221001 NES 221001 We read with great interest the article by Brusilovskaya et al. regarding the assessment of platelet activation in peripheral vs. jugular venous blood of cirrhotic patients by evaluation of surface expression of P-selectin and activated glycoprotein (GP) IIb/IIIa in response to different agonists [[1]]. [Extracted from the article]

Flexible optical networks require reconfigurable devices with operation on a wavelength range of several tens of nanometers, hitless tuneability (i.e. transparency to other channels during reconfiguration), and polarization independence. All these requirements have not been achieved yet in a single photonic integrated device and this is the reason why the potential of integrated photonics is still largely unexploited in the nodes of optical communication networks. Here we report on a fully-reconfigurable add-drop silicon photonic filter, which can be tuned well beyond the extended C-band (almost 100 nm) in a complete hitless (>35 dB channel isolation) and polarization transparent (1.2 dB polarization dependent loss) way. This achievement is the result of blended strategies applied to the design, calibration, tuning and control of the device. Transmission quality assessment on dual polarization 100 Gbit/s (QPSK) and 200 Gbit/s (16-QAM) signals demonstrates the suitability for dynamic bandwidth allocation in core networks, backhaul networks, intra- and inter-datacenter interconnects. Reconfigurable wavelength-selective devices are essential components of flexible optical networks. Here the authors show a silicon-photonic add-drop multiplexer meeting the strict requirements of telecom systems in terms of broadband operation range, hitless tunability and polarization transparency. [ABSTRACT FROM AUTHOR]

A study published in Liver International investigated whether von Willebrand factor (vWF) could predict short-term mortality in patients with acute-on-chronic liver failure (ACLF). The study included 51 patients with ACLF and measured vWF levels at admission. The researchers found that vWF was not associated with 30-day mortality and did not differ between patients who died and those who survived. The study suggests that further research is needed to confirm the prognostic role of vWF in ACLF. The study was funded by the Italian Ministry of Education, University, and Research and was approved by the Padova University Hospital Ethical Committee. [Extracted from the article]

SUMMARY: Patients with hepatocellular carcinoma (HCC) are at high risk of second primary malignancies. As HCC has become the leading indication of liver transplant (LT), the aim of this study was to investigate whether the presence of HCC before LT could influence the onset of de novo malignancies (DNM). A cohort study was conducted on 2653 LT recipients. Hazard ratios (HR) of DNM development for patients transplanted for HCC (HCC patients) were compared with those of patients without any previous malignancy (non‐HCC patients). All models were adjusted for sex, age, calendar year at transplant, and liver disease etiology. Throughout 17 903 person‐years, 6.6% of HCC patients and 7.4% of non‐HCC patients developed DNM (202 cases). The median time from LT to first DNM diagnosis was shorter for solid tumors in HCC patients (2.7 vs 4.5 years for HCC and non‐HCC patients, respectively, P < 0.01). HCC patients were at a higher risk of bladder cancer and skin melanoma. There were no differences in cumulative DNM‐specific mortality by HCC status. This study suggests that primary HCC could be a risk factor for DNM in LT recipients, allowing for risk stratification and screening individualization. [ABSTRACT FROM AUTHOR]

Real‐time control of multiple cascaded devices is a key requirement for the development of complex silicon photonic circuits performing new sophisticated optical functionalities. This article describes how the dithering technique can be leveraged in combination with non‐invasive light probes to independently control the working point of many photonic components. The standard technique is extended by introducing the concept of orthogonal dithering signals to simultaneously discriminate the effect of different actuators, while the idea of frequency re‐use is discussed to limit the complexity of control systems in cascaded architectures. After a careful analysis of the problem, the article presents an automated feedback strategy to tune and lock photonic devices in the maxima/minima of their transfer functions with given response speed and sensitivity. The trade‐offs of this approach are discussed in detail to provide guidelines for the design of the feedback loop. Experimental demonstrations on a mesh of Mach‐Zehnder interferometers and on cascaded ring resonators are discussed to validate the proposed control architecture in different scenarios and applications. [ABSTRACT FROM AUTHOR]