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Bacterial infection is a frequent trigger of acute-on-chronic liver failure (ACLF), syndrome that could also increase the risk of infection. This investigation evaluated prevalence and characteristics of bacterial and fungal infections causing and complicating ACLF, predictors of follow-up bacterial infections and impact of bacterial infections on survival.Patients407 patients with ACLF and 235 patients with acute decompensation (AD).Results152 patients (37%) presented bacterial infections at ACLF diagnosis; 46%(n=117) of the remaining 255 patients with ACLF developed bacterial infections during follow-up (4 weeks). The corresponding figures in patients with AD were 25% and 18% (p<0.001). Severe infections (spontaneous bacterial peritonitis, pneumonia, severe sepsis/shock, nosocomial infections and infections caused by multiresistant organisms) were more prevalent in patients with ACLF. Patients with ACLF and bacterial infections (either at diagnosis or during follow-up) showed higher grade of systemic inflammation at diagnosis of the syndrome, worse clinical course (ACLF 2-3 at final assessment: 47% vs 26%; p<0.001) and lower 90-day probability of survival (49% vs 72.5%;p<0.001) than patients with ACLF without infection. Bacterial infections were independently associated with mortality in patients with ACLF-1 and ACLF-2. Fungal infections developed in 9 patients with ACLF (2%) and in none with AD, occurred mainly after ACLF diagnosis (78%) and had high 90-day mortality (71%).ConclusionBacterial infections are extremely frequent in ACLF. They are severe and associated with intense systemic inflammation, poor clinical course and high mortality. Patients with ACLF are highly predisposed to develop bacterial infections within a short follow-up period and could benefit from prophylactic strategies.

Acute-on-chronic liver failure (ACLF) is characterized predominantly by non-apoptotic forms of hepatocyte cell death. Necroptosis is a form of programmed lytic cell death in which receptor interacting protein kinase (RIPK) 1, RIPK3 and phosphorylated mixed lineage kinase domain-like (pMLKL) are key components. This study was performed to determine the role of RIPK1 mediated cell death in ACLF. RIPK3 plasma levels and hepatic expression of RIPK1, RIPK3, and pMLKL were measured in healthy volunteers, stable patients with cirrhosis, and in hospitalized cirrhotic patients with acutely decompensated cirrhosis, with and without ACLF (AD). The role of necroptosis in ACLF was studied in two animal models of ACLF using inhibitors of RIPK1, necrostatin-1 (NEC-1) and SML2100 (RIPA56). Plasma RIPK3 levels predicted the risk of 28- and 90-day mortality (AUROC, 0.653 (95%CI 0.530–0.776), 0.696 (95%CI 0.593–0.799)] and also the progression of patients from no ACLF to ACLF [0.744 (95%CI 0.593–0.895)] and the results were validated in a 2 nd patient cohort. This pattern was replicated in a rodent model of ACLF that was induced by administration of lipopolysaccharide (LPS) to bile-duct ligated rats and carbon tetrachloride-induced fibrosis mice administered galactosamine (CCL 4 /GalN). Suppression of caspase-8 activity in ACLF rodent model was observed suggesting a switch from caspase-dependent cell death to necroptosis. NEC-1 treatment prior to administration of LPS significantly reduced the severity of ACLF manifested by reduced liver, kidney, and brain injury mirrored by reduced hepatic and renal cell death. Similar hepato-protective effects were observed with RIPA56 in a murine model of ACLF induced by CCL 4 /GalN. These data demonstrate for the first time the importance of RIPK1 mediated cell death in human and rodent ACLF. Inhibition of RIPK1 is a potential novel therapeutic approach to prevent progression of susceptible patients from no ACLF to ACLF.

In recent years, thanks to policies oriented toward the rehabilitation of existing heritage and the introduction of more environmentally sustainable choices, an increased attention has been devoted to the study of new structural strengthening solutions. With reference to masonry buildings, which constitute a significant part of the built heritage, Fiber Reinforced Cementitious Matrix (FRCM) systems are widely adopted to achieve more effective structural capacity, making use of inorganic matrices and composite grids, the latter being formed of carbon, basalt, glass, or aramid fibers. However, the necessity to reduce the carbon emissions, also considering the new European perspectives on sustainability, have prompted the scientific and engineering community to explore eco-friendly alternatives. In this context, the use of natural fibers as potential alternatives for enhancing the structural performance of a building or part of it, rises as a promising area of study. The present study proposes an analysis on the use of flax fibers within FRCM systems, aimed at reinforcing masonry structures. The mechanical and durability properties of the material are investigated through tensile tests on flax yarns, as well as tests on a fabric composed by flax bundles supported by a mesh of glass fibers. The results obtained in this study shaw how the natural type of fiber studied is so interested when it is treated with coating in terms of mechanical properties and durability.

Techniques such as retroperitoneal graft placement have further enhanced the ability to replicate the physiology of the “native” pancreas. In our center, from January 2000, duodenojejunostomy (DJ) was the standard technique for exocrine drainage (n = 337). Herein, we report a series of 188 pancreas transplantations performed between May 2016 to July 2025, using a fully retrocolic graft position, systemic venous drainage and enteric drainage via duodenoduodenostomy. The primary endpoint was the assessment of intestinal events and their impact on graft and patient survival. A total of 14 patients (7.4%) experienced complications, including paralytic ileus (n = 2), intestinal obstruction (n = 4), duodenal dehiscence following pancreas transplantectomy (n = 1), anastomotic dehiscence (n = 5), and anastomotic bleeding (n = 2). Of these, 11 cases required relaparotomy for adhesiolysis (n = 2), internal hernia repair (n = 1), Hartmann’s procedure (n = 1), transplantectomy (n = 2), primary leak closure (n = 3), and hemostasis with duodenal re-anastomosis (n = 2). After a median follow-up of 42.8 months [IQR 21.8–71.1], graft survival at 1 and 5 years was 87% and 83.4%, respectively (P = 0.688 vs. DJ group), while patient survival was 100% and 98.2% (P = 0.031 vs. DJ group). Duodenoduodenostomy proved to be a feasible and effective technique, offering competitive outcomes in terms of graft and patient survival.

Background In the present study, the surgeon aimed to align the stem at 5° to 25° in anteversion. The robotic technology was used to measure stem anteversion with respect to proximal femur anteversion at different levels down the femur. Methods A total of 102 consecutive patients underwent robotic-arm-assisted total hip arthroplasty (RTHA). 3D CT-based preoperative planning was performed to determine femoral neck version (FNV), posterior cortex anteversion (PCA), anterior cortex anteversion (ACA), and femoral metaphyseal axis anteversion (MAA) at 3 different levels: D (10 mm above lesser trochanter), E (the midpoint of the planned neck resection line) and F (head-neck junction). The robotic system was used to define and measure stem anteversion during surgery. Results Mean FNV was 6.6° (SD: 8.8°) and the mean MAA was consistently significantly higher than FNV, growing progressively from proximal to distal. Mean SV was 16.4° (SD: 4.7°). There was no statistically significant difference ( P  = 0.16) between SV and MAA at the most distal measured level. In 96.1% cases, the stem was positioned inside the 5°–25° anteversion range. Conclusions Femoral anteversion progressively increased from neck to proximal metaphysis. Aligning the stem close to femoral anteversion 10 mm above the lesser trochanter often led to the desired component anteversion.

Background: Acute-on-chronic liver failure (ACLF) is a common complication of cirrhosis characterized by single or multiple organ failures and high short-term mortality. Treatment of ACLF consists of standard medical care (SMC) and organ(s) support. Whether the efficacy of artificial liver support (ALS) depends on the severity of ACLF or on the intensity of this treatment, or both, is unclear. This study aimed to further assess these issues. Methods: We performed an individual patient data meta-analysis assessing the efficacy of Molecular Adsorbent Recirculating System (MARS) in ACLF patients enrolled in prior randomized control trials (RCTs). The meta-analysis was designed to assess the effect of patient severity (ACLF grade) and treatment intensity [low-intensity therapy (LIT), SMC alone or SMC plus ⩽ 4 MARS sessions, high-intensity therapy (HIT), SMC plus > 4 MARS sessions] on mortality. Results: Three RCTs suitable for the meta-analysis (n = 285, ACLF patients = 165) were identified in a systematic review. SMC plus MARS (irrespective of the number of sessions) did not improve survival compared with SMC alone, neither in the complete population nor in the ACLF patients. Survival, however, was significantly improved in the subgroup of patients receiving HIT both in the entire cohort (10-day survival: 98.6% versus 82.8%, p = 0.001; 30-day survival: 73.9% versus 64.3%, p = 0.032) and within the ACLF patients (10-day survival: 97.8% versus 78.6%, p = 0.001; 30-day survival: 73.3% versus 58.5%, p = 0.041). Remarkably, HIT increased survival independently of ACLF grade. Independent predictors of survival were age, Model for End-Stage Liver Disease (MELD), ACLF grade, number of MARS sessions received, and intensity of MARS therapy. Conclusion: HIT with albumin dialysis may improve survival in patients with ACLF. Appropriate treatment schedules should be determined in future clinical trials.

Background The effect of enzalutamide on health-related quality of life (HRQoL) in the PREVAIL trial in chemotherapy-naïve men with metastatic castration-resistant prostate cancer was analyzed using the generic EQ-5D instrument. Methods Patients received oral enzalutamide 160 mg/day ( n  = 872) or placebo ( n  = 845). EQ-5D index and EQ-5D visual analogue scale (EQ-5D VAS) scores were evaluated at baseline, week 13, and every 12 weeks until week 61 due to sample size reduction thereafter. Changes on individual dimensions were assessed, and Paretian Classification of Health Change (PCHC) and time-to-event analyses were conducted. Results With enzalutamide, EQ-5D index and EQ-5D VAS scores declined more slowly versus placebo and time to diverge from full health was prolonged. Average decline in EQ-5D index (−0.042 vs. –0.070; P  < .0001) and EQ-5D VAS (−1.3 vs. –4.4; P  < .0001) was significantly smaller with enzalutamide. There were significant ( P  < .05) between-group differences favoring enzalutamide in Pain/Discomfort to week 37, Anxiety/Depression at week 13, and Usual Activities at week 25, but no significant differences for Mobility and Self-care. The PCHC analysis showed more enzalutamide patients reporting improvement than placebo patients at weeks 13, 25, and 49 (all P  < .05) and week 37 ( P  = .0512). Enzalutamide was superior ( P  ≤ .0003) to placebo for time to diverge from full health and time to first deterioration on Pain/Discomfort and Anxiety/Depression dimensions. Conclusions This in-depth post hoc analysis showed that enzalutamide delayed HRQoL deterioration and had beneficial effects on several HRQoL domains, including Pain/Discomfort and the proportion of patients in full health, compared with placebo, and may help to support future analyses of this type. Trial registration NCT01212991

Background The FACT-8D is a new cancer-specific, preference-based measure (PBM) of health, derived from the Functional Assessment of Cancer Therapy – General (FACT-G) questionnaire. The FACT-8D’s measurement properties have not been tested to date. We assessed it’s validity and responsiveness in relapsed/refractory mantle cell lymphoma (RR MCL) and compared the results to the EQ-5D-5L. Methods Blinded analysis of pooled data from a phase 3 clinical trial. FACT-8D baseline and follow-up data (weeks 4, 7, 16, 31) were scored using Australian preference weights, the first available value-set. Convergent validity was assessed by estimating baseline correlations with the FACT-Lym total score, Trial Outcome Index (TOI), FACT-Lym lymphoma-specific sub-scale (LymS), EQ-5D Visual Analog Scale (VAS), and haemoglobin (HgB). Relevant clinical variables were used to categorise patients to test known groups’ validity and responsiveness was investigated using data from baseline ( n  = 250) and week 31 ( n  = 130). Results were compared with EQ-5D-5L, scored using the UK 3L crosswalk and the 5L England value-sets. Results The FACT-8D showed good convergent validity and responsiveness; baseline Pearson correlation coefficients between FACT-8D Index scores and other PRO measures were moderate to very strong (range: 0.49 for the EQ-VAS to 0.79 for FACT TOI) and the size of the change in FACT-8D Index scores at week 31 differed significantly ( p  < 0.005) between patients categorised as improved, worsened or stable using the FACT-Lym total score, LymS, and HgB. However, when assessing known groups’ validity, FACT-8D failed to discriminate between patients categorised by health status on four of the seven variables analysed. Overall, FACT-8D and EQ-5D-5L performed similarly, although EQ-5D-5L showed better known groups’ validity. Conclusions This is the first investigation into the psychometric properties of the FACT-8D. In this RR MCL trial dataset, it showed good convergent validity and responsiveness, but poorer known groups’ validity, and EQ-5D performed as well or better on the tests conducted. The FACT-8D may offer an alternative method to generate utilities for the cost-effectiveness analysis of cancer treatments but needs further testing in other types of cancer patients. Evaluation of utility gains may have been limited by high baseline performance status in this RR MCL trial sample.

IntroductionFunctional alignment (FA) in total knee arthroplasty (TKA) has been introduced to restore the native joint line obliquity, respect the joint line height and minimize the need of soft tissue releases. The purpose of this study was to assess the intraoperative joint line alignment and compare it with the preoperative epiphyseal orientation of the femur and tibia in patients undergoing robotic-arm-assisted (RA)-TKA using FA.Materials and MethodsThis retrospective study included a consecutive series of patients undergoing RA-TKA between February 2019 and February 2021. The joint line orientation of the femur and tibia in the three-dimensions was calculated and classified on preoperative CT-scans and compared with the intraoperative implant alignment. The tibial cut was performed according to the tibial preoperative anatomy. The femoral cuts were fine-tuned based on tensioned soft tissues, aiming for balanced medial and lateral gaps in flexion and extension.ResultsA total of 115 RA-TKAs were assessed. On average, the tibial component was placed at 1.8° varus (SD 1.3), while the femur was placed at 0.8° valgus (SD 2.2) and 0.6° external rotation (SD 2.6) relative to the surgical transepicondylar axis. Moderate to strong, statistically significant relationships were described between preoperative tibial coronal alignment and tibial cut orientation (r = 0.7, p < 0.0001), preoperative femoral orientation in the coronal and axial planes and intraoperative femoral cuts alignment (r = 0.7, p < 0.0001 and r = 0.5, p < 0.0001, respectively). One case (0.9%) of slight tibial component varus subsidence was reported 45-days post-operatively, but implant revision was not necessary.ConclusionsThe proposed robotic-assisted functional technique for TKA alignment, with a restricted tibial component coronal alignment, based on the preoperative phenotype and femoral component positioning as dictated by the soft tissues, provided joint line respecting resections. Further studies are needed to assess long-term implant survivorship, patient satisfaction and alignment-related failures.