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Background & Aims: Sarcopenia is associated with increased morbidity and mortality in patients with cirrhosis, but its definition in current literature is very heterogeneous. We performed a systematic review and meta-analysis to assess the association between mortality and sarcopenia evaluated by computed tomography (CT) in patients with cirrhosis, both overall and stratified for the criteria used to define sarcopenia. Methods: Medline, Embase, Scopus, and Cochrane Library were searched up to January 2023. We included studies assessing sarcopenia presence with CT scans and providing data on the risk of mortality. Adjusted hazard ratios (HRs) and 95% CIs were pooled using a random-effects model. Results: Thirty-nine studies comprising 12,827 patients were included in the meta-analysis. The summary prevalence of sarcopenia was 44% (95% CI 38-50%). The presence of sarcopenia (any definition) was an independent predictor of mortality with an adjusted HR of 2.07 (95% CI 1.81-2.36), and the result was consistent in all subgroup analyses. The prognostic role of the EASL/AASLD criteria was confirmed for the first time with an HR of 1.86 (95% CI 1.53-2.26) (n = 14 studies). The cut-offs used to define sarcopenia based on psoas muscle parameters varied among studies, thus, a subgroup analysis was not feasible. There was no substantial heterogeneity for the main estimates and no significant risk of publication bias. Conclusions: Sarcopenia on CT is associated with a 2-fold higher risk of mortality in patients with cirrhosis. The cut-offs proposed by EASL/AASLD are prognostically relevant and should be the recommended criteria used to define sarcopenia in clinical practice. Impact and implications:: Sarcopenia assessed by the reference standard (computed tomography scan) is an independent predictor of mortality in patients with cirrhosis, with a 2-fold increase in the risk of death in all sensitivity analyses. This finding is particularly valid in patients from Europe and North America, and in transplant candidates. Stratifying for the parameters and cut-offs used, we confirmed for the first time the prognostic impact of the definition proposed by EASL/AASLD, supporting their use in clinical practice. Psoas muscle assessment is promising, but data are still limited and too heterogeneous to recommend its routine use at present.

Background and objective: No clear-cut markers for predicting positive sperm retrieval (+SR) at microdissection testicular sperm extraction (mTESE) have been identified thus far. Our aim was to conduct a systematic review and meta-analysis to evaluate the ability of follicle-stimulating hormone (FSH), inhibin B (InhB), and anti-Müllerian hormone (AMH) to predict +SR in men with nonobstructive azoospermia (NOA) undergoing mTESE. Methods: We performed a search in the PubMed, EMBASE, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Thirty-four publications were selected for inclusion in the analysis. Key findings and limitations: Overall, the mean +SR rate was 45%. Pooled standardized mean difference (SMD) values revealed significant hormonal differences between the +SR and −SR groups, with lower FSH (SMD −0.30), higher InhB (SMD 0.54), and lower AMH (SMD −0.56) levels in the +SR group. Pooled odds ratios (Ors) revealed no significant prediction of +SR by either FSH (OR 1.03, 95% confidence interval [CI] 1.00–1.06) or InhB (OR 1.01, 95% CI 1.00–1.02), despite variations in baseline levels and study heterogeneity. Conversely, AMH had significant predictive value (OR 0.82, 95% CI 0.73–0.92), with lower baseline levels in the +SR group. InhB and FSH levels were higher in the +SR group, while InhB exhibited the opposite trend. Conclusions and clinical implications: Despite study heterogeneity, our meta-analysis findings support the ability of AMH to predict +SR for men with NOA undergoing mTESE. Patient summary: We conducted a review and analysis of results from previous studies. Our findings show that for men with an infertility condition called nonobstructive azoospermia, blood levels of anti-Müllerian hormone can predict successful extraction of sperm using a microsurgical technique. Levels of two other hormones did not predict successful sperm extraction.

Abstract Background Cancer-associated fibroblasts (CAFs) play a significant role in fueling prostate cancer (PCa) progression by interacting with tumor cells. A previous gene expression analysis revealed that CAFs up-regulate genes coding for voltage-gated cation channels, as compared to normal prostate fibroblasts (NPFs). In this study, we explored the impact of antiarrhythmic drugs, known cation channel inhibitors, on the activated state of CAFs and their interaction with PCa cells. Methods The effect of antiarrhythmic treatment on CAF activated phenotype was assessed in terms of cell morphology and fibroblast activation markers. CAF contractility and migration were evaluated by 3D gel collagen contraction and scratch assays, respectively. The ability of antiarrhythmics to impair CAF-PCa cell interplay was investigated in CAF-PCa cell co-cultures by assessing tumor cell growth and expression of epithelial-to-mesenchymal transition (EMT) markers. The effect on in vivo tumor growth was assessed by subcutaneously injecting PCa cells in SCID mice and intratumorally administering the medium of antiarrhythmic-treated CAFs or in co-injection experiments, where antiarrhythmic-treated CAFs were co-injected with PCa cells. Results Activated fibroblasts show increased membrane conductance for potassium, sodium and calcium, consistently with the mRNA and protein content analysis. Antiarrhythmics modulate the expression of fibroblast activation markers. Although to a variable extent, these drugs also reduce CAF motility and hinder their ability to remodel the extracellular matrix, for example by reducing MMP-2 release. Furthermore, conditioned medium and co-culture experiments showed that antiarrhythmics can, at least in part, reverse the protumor effects exerted by CAFs on PCa cell growth and plasticity, both in androgen-sensitive and castration-resistant cell lines. Consistently, the transcriptome of antiarrhythmic-treated CAFs resembles that of tumor-suppressive NPFs. In vivo experiments confirmed that the conditioned medium or the direct coinjection of antiarrhythmic-treated CAFs reduced the tumor growth rate of PCa xenografts. Conclusions Collectively, such data suggest a new therapeutic strategy for PCa based on the repositioning of antiarrhythmic drugs with the aim of normalizing CAF phenotype and creating a less permissive tumor microenvironment.

The health inequalities experienced by ethnic minorities have been a persistent and global phenomenon. The diagnosis of different types of skin conditions, e.g., melanoma, among people of color is one of such health domains where misdiagnosis can take place, potentially leading to life-threatening consequences. Although Caucasians are more likely to be diagnosed with melanoma, African Americans are four times more likely to present stage IV melanoma due to delayed diagnosis. It is essential to recognize that additional factors such as socioeconomic status and limited access to healthcare services can be contributing factors. African Americans are also 1.5 times more likely to die from melanoma than Caucasians, with 5-year survival rates for African Americans significantly lower than for Caucasians (72.2% vs. 89.6%). This is a complex problem compounded by several factors: ill-prepared medical practitioners, lack of awareness of melanoma and other skin conditions among people of colour, lack of information and medical resources for practitioners’ continuous development, under-representation of people of colour in research, POC being a notoriously hard to reach group, and ‘whitewashed’ medical school curricula. Whilst digital technology can bring new hope for the reduction of health inequality, the deployment of artificial intelligence in healthcare carries risks that may amplify the health disparities experienced by people of color, whilst digital technology may provide a false sense of participation. For instance, Derm Assist, a skin diagnosis phone application which is under development, has already been criticized for relying on data from a limited number of people of color. This paper focuses on understanding the problem of misdiagnosing skin conditions in people of color and exploring the progress and innovations that have been experimented with, to pave the way to the possible application of big data analytics, artificial intelligence, and user-centred technology to reduce health inequalities among people of color.

Abstract Objectives The objective of this study is to evaluate the prevalence and the importance of preperitoneal vas deferens (VD) infiltration in high‐risk prostate cancer (PCa). Patients and Methods In this prospectively designed study, we included 332 high‐risk PCa patients with a Briganti score >5%, who were treated by robot‐assisted radical prostatectomy between July 2017 and February 2022 at the Urology Department, SLK Kliniken Heilbronn. In addition to the standard histological analysis of the distal VD, which was attached to the prostate specimen, we analysed the infiltration status of preperitoneal VD in this cohort. The preperitoneal VD, which represents the middle part of ductus deferens and extends between the internal inguinal ring and obturator fossa, was resected during extended pelvic lymphadenectomy. Distal and preperitoneal VD status was registered together with preoperative and postoperative disease characteristics. Descriptive analysis methods and logistic regression analysis were used. Results Briganti score of the target cohort had a median value of 19%, while 235 patients (70.8%) of the group demonstrated a locally advanced disease. The Grade Group at prostatectomy specimen was at least 3 for 286 patients (86.1%). Distal VD infiltration was found in 20 patients (6%) and preperitoneal VD infiltration in two patients (0.6%). Distal VD infiltration was not associated with an increased possibility for positive surgical margins or nodal status among pT3b patients, while both patients with preperitoneal VD infiltration were characterized by highly aggressive disease in locally advanced stage and bilateral distal VD infiltration. Conclusions PCa extension along VD may reach a more proximal point of VD than the reported from the existing data infiltration of VD adjacent to seminal vesicles. This rare manifestation of PCa local extension may be the intermediate step to the rare cases of recurrence in the testicles. However, more robust data are needed to confirm the aforementioned hypothesis. Distal VD infiltration seems to have no additional prognostic value among patients with infiltrated seminal vesicles.

Objectives: The study measures trends in the profile of patients with chronic hepatitis B virus linked to care in Italy. Methods: A cross-sectional, multicenter, observational cohort (PITER cohort) of consecutive patients with hepatitis B surface antigen (HBsAg) over the period 2019-2021 from 46 centers was evaluated. The reference was the MASTER cohort collected over the years 2012-2015. Standard statistical methods were used. Results: The PITER cohort enrolled 4583 patients, of whom 21.8% were non-Italian natives. Compared with those in MASTER, the patients were older and more often female. The prevalence of hepatitis B e antigen (HBeAg) declined (7.2% vs 12.3; P

Background & Aims: We aimed to evaluate the impact of oesophageal varices (OV) and their evolution on the risk of complications of compensated advanced chronic liver disease (cACLD) caused by non-alcoholic fatty liver disease (NAFLD). We also assessed the accuracy of non-invasive scores for predicting the development of complications and for identifying patients at low risk of high-risk OV. Methods: We performed a retrospective assessment of 629 patients with NAFLD-related cACLD who had baseline and follow-up oesophagogastroduodenoscopy and clinical follow-up to record decompensation, portal vein thrombosis (PVT), and hepatocellular carcinoma. Results: Small and large OV were observed at baseline in 30 and 15.9% of patients, respectively. The 4-year incidence of OV from absence at baseline, and that of progression from small to large OV were 16.3 and 22.4%, respectively. Diabetes and a ≥5% increase in BMI were associated with OV progression. Multivariate Cox regression revealed that small (hazard ratio [HR] 2.24, 95% CI 1.47–3.41) and large (HR 3.86, 95% CI 2.34–6.39) OV were independently associated with decompensation. When considering OV status and trajectories, small (HR 2.65, 95% CI 1.39–5.05) and large (HR 4.90, 95% CI 2.49–9.63) OV at baseline and/or follow-up were independently associated with decompensation compared with the absence of OV at baseline and/or follow-up. The presence of either small (HR 2.8, 95% CI 1.16–6.74) or large (HR 5.29, 95% CI 1.96–14.2) OV was also independently associated with incident PVT. Conclusion: In NAFLD-related cACLD, the presence, severity, and evolution of OV stratify the risk of developing decompensation and PVT. Impact and implications: Portal hypertension is the main driver of liver decompensation in chronic liver diseases, and its non-invasive markers can help risk prediction. The presence, severity, and progression of oesophageal varices stratify the risk of complications of non-alcoholic fatty liver disease. Easily obtainable laboratory values and liver stiffness measurement can identify patients at low risk for whom endoscopy may be withheld, and can also stratify the risk of liver-related complications.

Abstract Background Rapid reductions in emissions from fossil fuel burning are needed to curb global climate change. Biofuel production from crop residues can contribute to reducing the energy crisis and environmental deterioration. Wheat is a renewable source for biofuels owing to the low cost and high availability of its residues. Thus, identifying candidate genes controlling these traits is pivotal for efficient biofuel production. Here, six multi-locus genome-wide association (ML-GWAS) models were applied using 185 tetraploid wheat accessions to detect quantitative trait nucleotides (QTNs) for fifteen traits associated with biomass composition. Results Among the 470 QTNs, only 72 identified by at least two models were considered as reliable. Among these latter, 16 also showed a significant effect on the corresponding trait (p.value

Objectives: Pneumocystis jirovecii pneumonia (PCP) incidence is increasing in people without HIV. Decompensated liver cirrhosis is not currently considered a risk factor for PCP. The aim of this paper is to describe a case series of patients with decompensated liver cirrhosis and PCP. Methods: All consecutive patients hospitalized with decompensated cirrhosis and microbiology-confirmed PCP at Policlinico Modena University Hospital from January 1, 2016 to December 31, 2021 were included in our series. Results: Eight patients were included. All patients had advanced-stage liver disease with a model for end-stage liver disease score above 15 (6/8 above 20). Four were on an active orthotopic liver transplant waiting list at the time of PCP diagnosis. Five patients did not have any traditional risk factor for PCP, whereas the other three were on glucocorticoid treatment for acute-on-chronic liver failure. All patients were treated with cotrimoxazole, except two who died before the diagnosis. Five patients died (62.5%), four of them within 30 days from PCP diagnosis. Of the remaining three, one patient underwent liver transplantation. Conclusion: Although further studies are needed, liver cirrhosis can be an independent risk factor for PCP in patients with decompensated cirrhosis that is mainly due to severe alcoholic hepatitis and who are on corticosteroids therapy, and primary prophylaxis for PCP should be considered.

Abstract In adult patients, acute lymphoblastic leukemia (ALL) is a rare hematological cancer with a cure rate below 50% and frequent relapses. With traditional therapies, patients with relapsed or refractory (R/R) ALL have a survival that may be measured in months; in these patients, inotuzumab ozogamicin (IO) is an effective therapy. IO was linked to increased risk of veno‐occlusive disease/sinusoid obstruction syndrome (VOD/SOS), liver injury, and various grade of liver‐related complications during clinical trials and real‐life settings; however, hepatologic monitoring protocol is not established in this population. In our institution, 21 patients who received IO (median of 6 doses of IO administered) for R/R ALL were prospectively followed for hepatologic surveillance, including clinical evaluation, ultrasonography, and liver stiffness measurement (LSM) biochemistry. After a median follow‐up of 17.2 months, two SOS events were reported (both after allogeneic transplant) as IO potentially related clinically relevant adverse event. Mild alterations were reported in almost the totality of patients and moderate‐severe liver biochemical alterations in a quarter of patients. Within biochemicals value, AST and ALP showed an augment related to IO administration. LSM linearly augmented for each IO course administered. Baseline LSM was related to liver‐related changes, especially with the severity of portal hypertension (PH)‐related complications. Pre‐transplant LSM was higher in patients receiving IO when compared with a control cohort. PH‐related complications were discovered in nearly 77% of patients, with clinically significant PH occurrence and development of ascites in 38% and 14%, respectively. This prospective experience constitutes the rationale to design a hepatologic monitoring program in patients receiving IO. LSM may be of pivotal importance in this program, constituting a rapid and effective screening that quantitatively correlates with liver alterations.

IntroductionThe study of immune response to SARSCoV-2 infection in different solid organ transplant settings represents an opportunity for clarifying the interplay between SARS-CoV-2 and the immune system. In our nationwide registry study from Italy, we specifically evaluated, during the first wave pandemic, i.e., in non-vaccinated patients, COVID-19 prevalence of infection, mortality, and lethality in liver transplant recipients (LTRs), using non-liver solid transplant recipients (NL-SOTRs) and the Italian general population (GP) as comparators.MethodsCase collection started from February 21 to June 22, 2020, using the data from the National Institute of Health and National Transplant Center, whereas the data analysis was performed on September 30, 2020.To compare the sex- and age-adjusted distribution of infection, mortality, and lethality in LTRs, NL-SOTRs, and Italian GP we applied an indirect standardization method to determine the standardized rate.ResultsAmong the 43,983 Italian SOTRs with a functioning graft, LTRs accounted for 14,168 patients, of whom 89 were SARS-CoV-2 infected. In the 29,815 NL-SOTRs, 361 cases of SARS-CoV-2 infection were observed. The geographical distribution of the disease was highly variable across the different Italian regions. The standardized rate of infection, mortality, and lethality rates in LTRs resulted lower compared to NL-SOTRs [1.02 (95%CI 0.81-1.23) vs. 2.01 (95%CI 1.8-2.2); 1.0 (95%CI 0.5-1.5) vs. 4.5 (95%CI 3.6-5.3); 1.6 (95%CI 0.7-2.4) vs. 2.8 (95%CI 2.2-3.3), respectively] and comparable to the Italian GP.DiscussionAccording to the most recent studies on SOTRs and SARS-CoV-2 infection, our data strongly suggest that, in contrast to what was observed in NL-SOTRs receiving a similar immunosuppressive therapy, LTRs have the same risk of SARS-CoV-2 infection, mortality, and lethality observed in the general population. These results suggest an immune response to SARS-CoV-2 infection in LTRS that is different from NL-SOTRs, probably related to the ability of the grafted liver to induce immunotolerance.