CAD/CAM Titanium Meshes for GBR: A Case Series with Preliminary Histologic Analysis.

Titanium has been proposed as a mesh material for guided bone regeneration (GBR) since the 1990s. To overcome difficulties in shaping and adapting meshes to the defect, digital techniques were introduced to digitally print meshes capable of fitting the bone perfectly, reproduced through the patient's CT scan. Five patients were included in this case series, and their CBCT data were acquired and sent to the producer of the titanium meshes. 3D regenerative surgery was performed with titanium meshes and a mix of demineralized bovine bone matrix (DBBM) and autogenous bone (1:1 ratio). Radiographic measures were evaluated on paraxial sections of the CBCT through a dedicated software. When possible, regenerated bone samples were obtained at implant insertion. Four out of five regenerated areas healed without local or systemic complications. One mesh was removed after 2 months and 2 weeks due to exposure. The mean vertical bone gain was 4.3 ± 1.5 mm (range: 2.5 to 7 mm). Two histologic samples were obtained. In sample 1, bone tissue area and graft material area were 44.4% and 12.5%, respectively; in sample 2, the same parameters were 15.6% and 16.9%, respectively.

PHOCUS: A Phase 3, Randomized, Open-Label Study of Sequential Treatment with Pexa-Vec (JX-594) and Sorafenib in Patients with Advanced Hepatocellular Carcinoma.

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, 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 the 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. 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.

Infective Endocarditis After Percutaneous Device Closure of Atrial Septal Defects: Incidence, Diagnosis, and Treatment. Case Report and Literature Review.

Infective endocarditis (IE) on atrial septal defect (ASD) closure devices, while extremely rare, has been reported to be more frequent early after the procedure. We describe a case of late IE after percutaneous closure of patent foramen ovale (PFO). We also performed a literature review on this subject. We reviewed a total of 42,365 patients who were treated with percutaneous devices: 13,916 for ostium secundum (OS) (32%), 24,726 for PFO (58%) and 3,723 for OS+PFO (8%). Among these patients, we identified 50 cases of IE after atrial septal defect device closure (0.001%). In contrast to previous reports, nearly 66% of IE in this setting occurred late, after at least 6 months from the procedure (33/50 patients). A statistical analysis clearly showed that the mean time from the procedure to IE increased in the last five years, probably associated with a change in antiplatelet therapy after ASD closure. Management of IE on an ASD occluder should always be discussed in the setting of a multidisciplinary heart team that includes a cardiologist, cardiac surgeon, and anesthetist. While surgical strategies gave excellent results, conservative management might be considered in cases of small IE vegetations and for patients in good general condition. However, in these cases, the patient must be closely observed with repeated blood and instrumental tests.

CAD-CAM Titanium Meshes for GBR: A Case Series with Preliminary Histological Analysis.

Titanium has been proposed as a mesh material for GBR since the nineties. To overcome difficulties in shaping and adaptation to the defect, digital elaboration techniques were introduced to digitally print meshes capable of fitting the bone perfectly, reproduced through the CT scan of the patient. Five patients were included in this case series. CBCT data of patients were acquired and sent to the producer of the titanium mesh. 3-dimension regenerative surgery was performed with titanium meshes and a mix of Demineralized Bovine Bone Matrix (DBBM) and Autologous bone (1:1 ratio). Radiographic measures were evaluated on paraxial sections of the CBCT through a dedicated software. When possible, regenerated bone samples were obtained at implant insertion time. Four out of five regenerated areas healed without local and systemic complications. One mesh was removed after two months and two weeks because of exposition. Mean vertical bone gain was 4.3 ± 1.5 mm (range 2.5 - 7 mm). Two histologic samples were obtained. In sample n.1, Bone Tissue Area and Graft Material Area were respectively 44.4% and 12.5%. In sample n.2, the same parameters were 15.6% and 16.9% respectively.

Implants Placed with the All-On-4 Technique: A Radiographic Retrospective Study on 156 Implants with a 5- to 14-Year Follow-up.

The aim of this retrospective study was to evaluate the performance of implants placed with the All-on-4 technique after a mean time in function of 9 years. A total of 34 patients with 156 implants were selected for this study: 18 patients underwent tooth extraction on the day of implant placement (Group D), and 16 patients were already edentulous (Group E). A periapical radiograph was taken at a mean follow-up of 9 years (range: 5 to 14 years). Success and survival rates and the prevalence of peri-implantitis were calculated. Statistical analysis was used to assess comparisons between groups. After a mean follow-up of 9 years, the cumulative survival rate was 97.4% and the success rate was 77.4%. The difference between the initial and final radiographs resulted in a mean marginal bone loss (MBL) of 1.3 ± 1.06 mm (range: 0.1 to 5.3 mm). No differences were seen between Groups D and E. Peri-implantitis affected 15 implants (9.6%) in 9 patients (26.5%). This study shows that the All-on-4 technique is a reliable treatment method for both edentulous patients and patients requiring tooth extractions, with results maintained over a long follow-up period. The present MBL results are similar to those around implants in other rehabilitation types.

Molecular Analysis With 16S rRNA PCR/Sanger Sequencing and Molecular Antibiogram Performed on DNA Extracted From Valve Improve Diagnosis and Targeted Therapy of Infective Endocarditis: A Prospective Study.

BACKGROUND: Molecular analysis (MA) on heart valve (HV) improves the microbiologic diagnosis of infectious endocarditis (IE). The main drawback of MA is the lack of antimicrobial susceptibility information. METHODS: We conducted a prospective cohort observational study of consecutive adult patients from April 2012 to May 2021 who underwent valve surgery at our hospital. The performance of MA, blood cultures (BC) and valve cultures (VC), and the diagnostic and therapeutic impact of MA were evaluated. Molecular antibiogram results were compared to culture-based antimicrobial susceptibility testing (AST). RESULTS: A total of 137 patients with definite IE and 52 patients with no IE were enrolled in the study. Among IE cases BC, VC, and MA were positive in 75 (55%), 30 (22%), and 120 (88%) of IE cases, respectively. Among 62 cases of BC-negative IE (BCNE), 57 achieved diagnosis with MA. MA led to a change of antimicrobial therapy in 92% of BCNE. MA was negative in 100% of patients with no IE. Molecular antibiogram performed on 17 valve specimens that resulted positive for pathogens potential carrier of genes encoding for multidrug resistant mechanisms showed 100% concordance with AST. CONCLUSIONS: MA showed a high specificity and sensitivity in etiological diagnosis of IE. Molecular antibiogram could overcome the major limitation of MA that is the lack of susceptibility testing. We advocate for the inclusion of MA among diagnostic criteria for IE and for a more extensive use of molecular antibiogram when the culture result is negative, and MA is the only positive test.

Right vs left portal branch puncture in TIPS creation with controlled expansion covered stent: comparison of hemodynamic and clinical outcomes.

PURPOSE: To retrospectively compare outcomes of TIPS performed by puncturing left portal vein (LPV) vs right portal vein (RPV) to access the portal system. MATERIALS AND METHODS: One hundred ninety-three consecutive patients underwent TIPS with controlled expansion covered stent by using the LPV (37 patients) or the RPV (156 patients). Patients were followed until the last clinical evaluation, liver transplantation, or death. RESULTS: Demographics and clinical characteristics of the two groups were comparable. The median follow-up was 9.6 months (range 0.1-50.6). Portosystemic pressure gradient (PSG) before TIPS 15.7 mmHg ± 4.7 in RPV group (RPVG) vs 15.4 mmHg ± 4.5 in LPV group (LPVG) (p = 0.725). After TIPS, PSG 6.3 mmHg ± 2.8 in RPVG vs 6.2 mmHg ± 2.2 (p = 0.839). In LPVG, the stent was dilated to 8-mm in 95% of patients vs 77% of RPVG (p = 0.015). Two (5.4%) and 22 (14%) patients underwent TIPS revision in LPVG and RPVG (p = 0.15). The incidence of overt HE was 13% in LPVG and 24% in RPVG (p = 0.177). Rebleeding occurred in 3 of 49 patients (6%) with variceal bleeding as an indication: 2/41 patients (4.9%) in RPVG vs 1/8 patients (12.5%) in LPVG (p = 0.417). Among 126 patients with refractory ascites 20 patients (15.9%) needed paracentesis 3 months after the procedure: 18/101 patients (17.8%) in RPVG vs 2/25 patients (8%) in LPVG (p = 0.231). Thirty-seven patients (19%) died: 32 (21%) in RPVG and 5 (14%) in LPVG (p = 0.337). CONCLUSION: Compared with RPV puncture, in TIPS created through the LPV, the targeted PSG was reached with a smaller stent diameter. However, no significant difference in clinical outcomes was observed. KEY POINTS: • A LPV approach for TIPS creation does not lead to better control of complications of portal hypertension as compared to a RPV approach.

Clinical outcomes of transjugular intrahepatic portosystemic shunt with PTFE-covered stents after liver transplantation and technical results in split and whole liver graft recipients.

OBJECTIVES: To assess the outcomes of transjugular intrahepatic portosystemic shunt (TIPS) creation using PTFE-covered stents in liver transplant (LT) recipients and to analyze the technical result of TIPS creation in split grafts (SG) compared with whole liver grafts (WG). METHODS AND MATERIALS: Single-center, retrospective study, analyzing LT patients who underwent TIPS using PTFE-covered stents. Clinical and technical variables were analyzed. RESULTS: Between 2005 and 2021, TIPS was created using PTFE-covered stents in 48 LT patients at a median of 43 months (range, 0.5-192) after LT. TIPS indications were refractory ascites (RA) in 33 patients (69%), variceal bleeding (VB) in 9 patients (19%), others in 6 (12%). Ten patients (21%) received a SG. Technical success rate was 100% in both groups: in two WG recipients, (5%) a second attempt was required. An unconventional approach (combined transhepatic or transplenic access) was needed in 2 WG (5%) and 2 SG recipients (20%). Two procedure-related death occurred in the WG group. After a median follow-up of 22 months (range, 0,1-144), 16 patients (48%) in the RA group did not require post-TIPS paracentesis, in the VB group rebleeding occurred in 3 patients (33%). Fifteen patients (31%) underwent TIPS revision. Overt hepatic encephalopathy occurred in 14 patients (29%). Patient survival at 6 months, 1 year, and 3 years was 77%, 66%, and 43%, respectively. CONCLUSIONS: The feasibility and safety of TIPS creation in SG are comparable to that of WG. TIPS creation using PTFE-covered stents represents a viable option to treat portal hypertensive complications in LT recipients. KEY POINTS: • TIPS creation using PTFE-covered stents represents a viable option to treat complications of PH in LT recipients. • TIPS creation in LT SG recipients appears to be safe and feasible as in WG. • Results from this study may help to refine the management of LT patients with recurrent portal hypertensive complications encouraging physicians to consider TIPS creation as a treatment option in both SG and WG recipients.

Reducing Carbapenem-Resistant Enterobacteriaceae Using the Targeted Solution Tool: A Quality Improvement Project.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) is a worldwide urgent health problem. Hand hygiene (HH) is an effective intervention to reduce the spread of CRE. LOCAL PROBLEM: In 2017, an increase in the rate of health care-associated (HA) CRE colonization was observed in a large multiorgan transplant center in Italy. This study aimed to reduce the HA-CRE colonization rates by improving HH compliance. METHODS: A pre-/post-intervention project was conducted from November 2017 through December 2020. INTERVENTIONS: The DMAIC (Define, Measure, Analyze, Improve, and Control) framework was used to implement the HH Targeted Solution Tool (TST). RESULTS: Hand hygiene compliance increased from 49% to 76.9% after the Improve phase ( P = .0001), and to 81.9% after the second Control phase ( P = .0001). The rate of HA-CRE decreased from 24.9% to 5.6% ( P = .0001). CONCLUSIONS: Using the DMAIC framework to implement the TST can result in significant improvements in HH compliance and HA-CRE colonization rates.

Donor Simvastatin Treatment Is Safe and Might Improve Outcomes After Liver Transplantation: A Randomized Clinical Trial.

BACKGROUND: The current curative approaches for ischemia/reperfusion injury on liver transplantation are still under debate for their safety and efficacy in patients with end-stage liver disease. We present the SIMVA statin donor treatment before Liver Transplants study. METHODS: SIMVA statin donor treatment before Liver Transplants is a monocentric, double-blind, randomized, prospective tial aiming to compare the safety and efficacy of preoperative brain-dead donors' treatment with the intragastric administration of 80 mg of simvastatin on liver transplant recipient outcomes in a real-life setting. Primary aim was incidence of patient and graft survival at 90 and 180 d posttransplant; secondary end-points were severe complications. RESULTS: The trial enrolled 58 adult patients (18-65 y old). The minimum follow-up was 6 mo. No patient or graft was lost at 90 or 180 d in the experimental group (n = 28), whereas patient/graft survival were 93.1% ( P = 0.016) and 89.66% ( P = 0.080) at 90 d and 86.21% ( P = 0.041) and 86.2% ( P = 0.041) at 180 d in the control group (n = 29). The percentage of patients with severe complications (Clavien-Dindo ≥IIIb) was higher in the control group, 55.2% versus 25.0% in the experimental group ( P = 0.0307). The only significant difference in liver tests was a significantly higher gamma-glutamyl transferase and alkaline phosphatase at 15 d ( P = 0.017), ( P = 0.015) in the simvastatin group. CONCLUSIONS: Donor simvastatin treatment is safe, and may significantly improve early graft and patient survival after liver transplantation, although further research is mandatory.

Brain magnetic resonance imaging radiomics features associated with hepatic encephalopathy in adult cirrhotic patients.

PURPOSE: Hepatic encephalopathy (HE) is a potential complication of cirrhosis. Magnetic resonance imaging (MRI) may demonstrate hyperintense T1 signal in the globi pallidi. The purpose of this study was to evaluate the performance of MRI-based radiomic features for diagnosing and grading chronic HE in adult patients affected by cirrhosis. METHODS: Adult patients with and without cirrhosis underwent brain MRI with identical imaging protocol on a 3T scanner. Patients without history of chronic liver disease were the control population. HE grading was based on underlying liver disease, severity of clinical manifestation, and number of encephalopathic episodes. Texture analysis was performed on axial T1-weighted images on bilateral lentiform nuclei at the level of the foramina of Monro. Diagnostic performance of texture analysis for the diagnosis and grading of HE was assessed by calculating the area under the receiver operating characteristics (AUROC) with 95% confidence interval (CI). RESULTS: The final study population consisted of 124 patients, 70 cirrhotic patients, and 54 non-cirrhotic controls. Thirty-eight patients had history of HE with 22 having an HE grade > 1. The radiomic features predicted the presence of HE with an AUROC of 0.82 (95% CI: 0.73, 0.90; P < .0001; 82% sensitivity, 66% specificity). Radiomic features predicted grade 1 HE (AUROC 0.75; 95% CI: 0.61, 0.89; P < .0001; 94% sensitivity, 60% specificity) and grade ≥ 2 HE (AUROC 0.82; 95% CI: 0.71, 0.93; P < .0001, 95% sensitivity, 57% specificity). CONCLUSION: In cirrhotic patients, MR radiomic is effective in predicting the presence of chronic HE and in grading its severity.

Impact of the Organizational Model Adopted during the COVID-19 Pandemic on the Perceived Safety of Intensive Care Unit Staff.

BACKGROUND: The SARS-CoV-2 pandemic had a devastating health, social, and economic effect on the population. Organizational, technical and structural operations aimed at protecting staff, outpatients and inpatients were implemented in an Italian hospital with a COVID-19 dedicated intensive care unit. The impact of the organizational model adopted on the perceived safety among staff was evaluated. METHODS: Descriptive, structured and voluntary, anonymous, non-funded, self-administered cross-sectional surveys on the impact of the organizational model adopted during COVID-19 on the perceived safety among staff. RESULTS: Response rate to the survey was 67.4% (153 completed surveys). A total of 91 (59%) of respondents had more than three years of ICU experience, while 16 (10%) were employed for less than one year. Group stratification according to profession: 74 nurses (48%); 12 medical-doctors (7%); 11 physiotherapists (7%); 35 nurses-aides (22%); 5 radiology-technicians (3%); 3 housekeeping (1%); 13 other (8%). The organizational model implemented at ISMETT made them feel safe during their workday. A total of 113 (84%) agreed or strongly agreed with the sense of security resulting from the implemented measures. A vast majority of respondents perceived COVID-19 as a dangerous and deadly disease (94%) not only for themselves but even more as vectors towards their families (79%). A total of 55% of staff took isolation measures and moved away from their home by changing personal habits. The organizational model was perceived overall as appropriate (91%) to guarantee their health. CONCLUSION: The vast majority of respondents perceived the overall model applied during an unexpected, emergency situation as appropriate.

How to Improve Patients' Perceived Quality of Sleep During Hospitalization Through a Multicomponent "Good Sleep Bundle": A Prospective Before and After Controlled Study.

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.

Liver transplantation from active COVID-19 donors: A lifesaving opportunity worth grasping?

COVID-19 pandemic dramatically impacted transplantation landscape. Scientific societies recommend against the use of donors with active SARS-CoV-2 infection. Italian Transplant Authority recommended to test recipients/donors for SARS-CoV-2-RNA immediately before liver transplant (LT) and, starting from November 2020, grafts from deceased donors with active SARS-CoV-2 infection were allowed to be considered for urgent-need transplant candidates with active/resolved COVID-19. We present the results of the first 10 LTs with active COVID-19 donors within an Italian multicenter series. Only two recipients had a positive molecular test at LT and one of them remained positive up to 21 days post-LT. None of the other eight recipients was found to be SARS-CoV-2 positive during follow-up. IgG against SARS-CoV-2 at LT were positive in 80% (8/10) of recipients, and 71% (5/7) showed neutralizing antibodies, expression of protective immunity related to recent COVID-19. In addition, testing for SARS-CoV-2 RNA on donors' liver biopsy at transplantation was negative in 100% (9/9), suggesting a very low risk of transmission with LT. Immunosuppression regimen remained unchanged, according to standard protocol. Despite the small number of cases, these data suggest that transplanting livers from donors with active COVID-19 in informed candidates with SARS-CoV-2 immunity, might contribute to safely increase the donor pool.

Performance of the model for end-stage liver disease score for mortality prediction and the potential role of etiology.

BACKGROUND & AIMS: Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model. METHODS: In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses. RESULTS: In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD. CONCLUSIONS: In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed. LAY SUMMARY: While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model.

Combination of aztreonam, ceftazidime-avibactam and amikacin in the treatment of VIM-1 Pseudomonas aeruginosa ST235 osteomyelitis.

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.