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Lung transplant recipients (LTRs) respond poorly to vaccination. SARS-CoV-2 pre-exposure prophylaxis (PrEP) with tixagevimab/cilgavimab (TIX/CIL) reduces the incidence of infection and the evolution to severe COVID-19. In vitro data show decreased activity against Omicron variants. We evaluated the clinical efficacy and safety of TIX/CIL in LTRs during the Omicron wave. A prospective observational cohort study was conducted at ISMETT in Palermo (Italy). In June 2022, SARS-CoV-2 PrEP with TIX/CIL 150/150 mg was offered to LTRs. LTRs who received TIX/CIL were compared to LTRs who did not. Logistic regression analysis (adjusted for prior COVID-19, SARS-CoV-2 vaccination, age, years from transplant, and rejection) was performed. The objective of this study was to compare the following among the two populations: prevalence of SARS-CoV-2, length of SARS-CoV-2 positivity, and COVID-19 disease severity. Among 110 eligible LTRs, 79 (72%) received TIX/CIL and 31 (28%) did not. SARS-CoV-2 infections occurred in 6% (n = 5) of patients who received TIX/CIL and 29% (n = 9) of patients who did not (p < 0.001). In both groups, infections were mild/asymptomatic, and no one was hospitalized or died. At multivariate analysis, TIX/CIL was associated with a lower risk of infection (aOR 0.22; 95%CI 0.06–0.78; p = 0.02). TIX/CIL was safe and effective in reducing the risk of SARS-CoV-2 in LTRs during the Omicron wave.

Introduction: Despite sound evidence on the importance of sleep for human beings and its role in healing, hospitalized patients still experience sleep disruption with deleterious effects. Many factors affecting patients’ sleep can be removed or minimized. We evaluated the efficacy of a multicomponent Good Sleep Bundle (GSB) developed to improve patients’ perceived quality of sleep, through which we modified environmental factors, timing of nighttime clinical interventions, and actively involved patients in order to positively influence their experience during hospitalization. Methods: In a prospective, before and after controlled study, two different groups of 65 patients each were admitted to a cardiothoracic unit in two different periods, receiving the usual care (control group) and the GSB (GSB group), respectively. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI) at the admission, discharge, and 30 days after discharge in all patients enrolled. Comparisons between the two groups evaluated changes in PSQI score from admission to discharge (primary endpoint), and from admission to 30 days after discharge (secondary endpoint). Results: The mean PSQI score difference between admission and discharge was 4.54 (SD 4.11) in the control group, and 2.05 (SD 4.25) in the GSB group. The mean difference in PSQI score change between the two groups, which was the primary endpoint, was 2.49 (SD 4.19). This difference was highly significant (p = 0.0009). Conclusion: The GSB was associated with a highly significant reduction of the negative effects that hospitalization produces on patients’ perceived quality of sleep compared with the usual care group.

Introduction Intratumoral administration of pexa-vec (Pexastimogene Devacirepvec), an oncolytic and immunotherapeutic vaccinia virus. given to patients with hepatocellular carcinoma (HCC), is associated with both local and distant tumor responses. We hypothesized subsequent treatment with sorafenib could demonstrate superior efficacy. Methods This random phase III open-label study evaluated the sequential treatment with pexa-vec followed by sorafenib compared to sorafenib in patients with advanced HCC and no prior systemic treatment. The primary endpoint is overall survival (OS). Key secondary endpoints included time to progression (TTP), progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR). Safety was assessed in all patients who received ≥ 1 dose of study treatment. Results The study was conducted at 142 sites in 16 countries. From December 30, 2015, to the interim analysis on August 2, 2019, 459 patients were randomly assigned (pexa-vec plus sorafenib 234, sorafenib: 225). At the interim analysis the median OS was 12.7 months (95% CI: 9.89, 14.95) in the pexa-vec plus sorafenib arm and 14.0 months (95% CI: 11.01, 18.00) in the sorafenib arm. This led to early termination of the study. The median TTP was 2.0 months (95% CI: 1.77, 2.96) and 4.2 months (95% CI: 2.92, 4.63); ORR was 19.2% (45 patients) and 20.9% (47 patients); and DCR was 50.0% (117 patients) and 57.3% (129 patients) in the pexa-vec plus sorafenib and sorafenib arms, respectively. Serious adverse events were reported in 117 (53.7%) patients in the pexa-vec plus sorafenib and 77 (35.5%) patients in the sorafenib arm. Liver failure was the most frequently reported in both groups. Discussion/Conclusion Sequential pexa-vec plus sorafenib treatment did not demonstrate increased clinical benefit in advanced HCC and fared worse compared to sorafenib alone. The advent of the added value of checkpoint inhibitors should direct any further development of oncolytic virus therapy strategies.

We describe a challenging case of patient with metallo-beta-lactamase-producing Pseudomonas aeruginosa sternal osteomyelitis following aortic valve replacement with biological prosthesis. The strain exhibited a multidrug-resistance phenotype carrying the blaVIM-1 gene and belonged to the high-risk clone sequence type ST235. The patient was successfully treated with surgical debridement plus antibiotic therapy with ceftazidime/avibactam, aztreonam, and amikacin. Time-kill curves showed that this triple antibiotic combination at 1 × MIC was strongly synergic after 8 h, achieving 99.9% killing and maintaining this until 48 h.

Abstract Background To evaluate incidence, risk factors, and outcomes of postoperative neurological complications in patients undergoing cardiac surgery. Methods A total of 2121 patients underwent cardiac surgery between August, 2008 and December, 2013; 91/2121 (4.3%) underwent brain computed tomography (70/91, 77%) or magnetic resonance imaging (21/91, 23%) scan because of major stroke (37/2121, 1.7%) and a spectrum of transient neurological episodes as well as transient ischemic attacks and delirium /psychosis/seizures (54/2121, 2.5%). The mean age was 65.3 ± 12.1 years and 60 (65.9%) were male. Variables were compared among study- and matched-patients (n = 113) without neurological deficits. Results A total of 37/2121 (1.7%) patients had imaging evidence of stroke. Radiological examinations were done 5.72 ± 3.6 days after surgery. Patients with and without imaging evidence of stroke had longer intensive care unit length of stay (LOS) (13.8 ± 14.7 and 12.9 ± 15 days vs. 5.7 ± 12.1 days, respectively (p

Abstract Background Liver transplantation is the best treatment for end-stage liver disease. The interruption of the blood supply to the donor liver during cold storage damages the liver, affecting how well the liver will function after transplant. The drug Simvastatin may help to protect donor livers against this damage and improve outcomes for transplant recipients. The aim of this study is to evaluate the benefits of treating the donor liver with Simvastatin compared with the standard transplant procedure. Patient and methods We propose a prospective, double-blinded, randomized phase 2 study of 2 parallel groups of eligible adult patients. We will compare 3-month, 6-month, and 12-month graft survival after LT, in order to identify a significant relation between the two homogenous groups of LT patients. The two groups only differ by the Simvastatin or placebo administration regimen while following the same procedure, with identical surgical instruments, and medical and nursing skilled staff. To reach these goals, we determined that we needed to recruit 106 patients. This sample size achieves 90% power to detect a difference of 14.6% between the two groups survival using a one-sided binomial test. Discussion This trial is designed to confirm the effectiveness of Simvastatin to protect healthy and steatotic livers undergoing cold storage and warm reperfusion before transplantation and to evaluate if the addition of Simvastatin translates into improved graft outcomes. Trial registration ISRCTN27083228.

Abstract Bronchiolitis Obliterans Syndrome is the major determinant of the graft function loss after lung transplantation, but its pathogenesis is still incompletely understood and currently available therapeutic strategies are poorly effective. A deeper understanding of its pathogenic mechanisms is crucial for the development of new strategies to prevent and treat this devastating complication. In this study, we focused on the mesenchymal stromal cells, recently recognized as BOS key effectors, and our primary aim was to identify their epigenetic determinants, such as histone modifications and non-coding RNA regulation, which could contribute to their differentiation in myofibroblasts. Interestingly, we identified a deregulated expression of histone deacetylases and methyltransferases, and a microRNA-epigenetic regulatory network, which could represent novel targets for anti-fibrotic therapy. We validated our results in vitro, in a cell model of fibrogenesis, confirming the epigenetic involvement in this process and paving the way for a new application for epigenetic drugs.

PURPOSEThe aim of this study was to evaluate the feasibility and safety of recanalization of occlusive transjugular intrahepatic portosystemic shunts (TIPS) that are inaccessible to the standard transvenous approach in patients with occlusive bare and covered stents. MATERIALS AND METHODSFrom July 1999 to July 2011, 430 consecutive TIPS were performed at a single institution in patients with chronic liver diseases and complications of portal hypertension. During the follow-up, a TIPS occlusion was detected in 20 cases that could not be crossed using a standard transvenous technique with a hydrophilic guidewire. RESULTSFive cases had a bare stent, and 15 cases had a covered stent. In 19 cases (95%), the Colapinto needle technique was used. The Colapinto needle was advanced at the mouth of the occluded TIPS (n=2) or within the thrombus in the middle-distal shunt (n=16) to provide aid in advancing the hydrophilic guidewire into the portal vein. In one patient, after failure of the Colapinto technique, the combined transhepatic and transvenous approach was used. All of the procedures were successfully performed without complications. CONCLUSIONIn patients with occlusive TIPS, stent recanalization is feasible and safe. The Colapinto needle technique should be used as the first approach, reserving the combined transhepatic and transvenous approach only for failure of this technique.

Fetal hepatocytes have a high regenerative capacity. The aim of the study was to assess treatment safety and clinical efficacy of human fetal liver cell transplantation through splenic artery infusion. Patients with endstage chronic liver disease on the waiting list for liver transplantation were enrolled. A retrospectively selected contemporary matched-pair group served as control. Nonsorted raw fetal liver cell preparations were isolated from therapeutically aborted fetuses. The end points of the study were safety and improvement of the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores. Nine patients received a total of 13 intrasplenic infusions and were compared with 16 patients on standard therapy. There were no side effects related to the infusion procedure. At the end of follow-up, the MELD score (mean ± SD) in the treatment group remained stable from baseline (16.0 ± 2.9) to the last observation (15.7 ± 3.8), while it increased in the control group from 15.3 ± 2.5 to 19 ± 5.7 ( p = 0.0437). The Child-Pugh score (mean ± SD) dropped from 10.1 ± 1.5 to 9.1 ± 1.4 in the treatment group and increased from 10.0 ± 1.2 to 11.1 ± 1.6 in the control group ( p = 0.0076). All treated patients with history of recurrent portosystemic encephalopathy (PSE) had no further episodes during 1-year follow-up. No improvement was observed in the control group patients with PSE at study inclusion. Treatment was considered a failure in six of the nine patients (three deaths not liver related, one liver transplant, two MELD score increases) compared with 14 of the 16 patients in the control group (six deaths, five of which were caused by liver failure, four liver transplants, and four MELD score increases). Intrasplenic fetal liver cell infusion is a safe and well-tolerated procedure in patients with end-stage chronic liver disease. A positive effect on clinical scores and on encephalopathy emerged from this preliminary study.

Compensatory renal hypertrophy following unilateral nephrectomy (UNX) occurs in the remaining kidney. However, the long-term cardiac adaptive process to UNX remains poorly defined in humans. Our goal was to characterize myocardial structure and function in living kidney donors (LKDs), approximately 12 years after UNX.Cardiac function and structure in 15 Italian LKDs, at least 5 years after UNX (median time from donation = 8.4 years) was investigated and compared to those of age and sex matched U.S. citizens healthy controls (n = 15). Standard and speckle tracking echocardiography (STE) was performed in both LKDs and controls. Plasma angiotensin II, aldosterone, atrial natriuretic peptide (ANP), N terminus pro B-type natriuretic peptide (NT-proBNP), cyclic guanylyl monophosphate (cGMP), and amino-terminal peptide of procollagen III (PIIINP) were also collected. Median follow-up was 11.9 years. In LKDs, LV geometry and function by STE were similar to controls, wall thickness and volumes were within normal limits also by CMR. In LKDs, CMR was negative for myocardial fibrosis, but apical rotation and LV torsion obtained by STE were impaired as compared to controls (21.4 ± 7.8 vs 32.7 ± 8.9 degrees, p = 0.04). Serum creatinine and PIIINP levels were increased [1.1 (0.9-1.3) mg/dL, and 5.8 (5.4-7.6)] μg/L, respectively), while urinary cGMP was reduced [270 (250-355) vs 581 (437-698) pmol/mL] in LKDs. No LKD developed cardiovascular or renal events during follow-up.Long-term kidney donors have no apparent structural myocardial abnormalities as assessed by contrast enhanced CMR. However, myocardial deformation of the apical segments, as well as apical rotation, and LV torsion are reduced. The concomitant increase in circulating PIIINP level is suggestive of fibrosis. Further studies, focused on US and EU patients are warranted to evaluate whether these early functional modifications will progress to a more compromised cardiac function and structure at a later time.