Computer-assisted dental implant placement following free flap reconstruction: virtual planning, CAD/CAM templates, dynamic navigation and augmented reality

Image-guided surgery, prosthetic-based virtual planning, 3D printing, and CAD/CAM technology are changing head and neck ablative and reconstructive surgical oncology. Due to quality-of-life improvement, dental implant rehabilitation could be considered in every patient treated with curative intent. Accurate implant placement is mandatory for prosthesis long-term stability and success in oncologic patients. We present a prospective study, with a novel workflow, comprising 11 patients reconstructed with free flaps and 56 osseointegrated implants placed in bone flaps or remnant jaws (iliac crest, fibula, radial forearm, anterolateral thigh). Starting from CT data and jaw plaster model scanning, virtual dental prosthesis was designed. Then prosthetically driven dental implacement was also virtually planned and transferred to the patient by means of intraoperative infrared optical navigation (first four patients), and a combination of conventional static teeth supported 3D-printed acrylic guide stent, intraoperative dynamic navigation, and augmented reality for final intraoperative verification (last 7 patients). Coronal, apical, and angular deviation between virtual surgical planning and final guided intraoperative position was measured on each implant. There is a clear learning curve for surgeons when applying guided methods. Initial only-navigated cases achieved low accuracy but were comparable to non-guided freehand positioning due to jig registration instability. Subsequent dynamic navigation cases combining highly stable acrylic static guides as reference and registration markers result in the highest accuracy with a 1-1.5-mm deviation at the insertion point. Smartphone-based augmented reality visualization is a valuable tool for intraoperative visualization and final verification, although it is still a difficult technique for guiding surgery. A fixed screw-retained ideal dental prosthesis was achieved in every case as virtually planned. Implant placement, the final step in free flap oncological reconstruction, could be accurately planned and placed with image-guided surgery, 3D printing, and CAD/CAM technology. The learning curve could be overcome with preclinical laboratory training, but virtually designed and 3D-printed tracer registration stability is crucial for accurate and predictable results. Applying these concepts to our difficult oncologic patient subgroup with deep anatomic alterations ended in comparable results as those reported in non-oncologic patients.This work was supported by grant PI18/01625 (Ministerio de Ciencia e Innovación-Instituto de Salud Carlos III and European Regional Development Fund "Una manera de hacer Europa"). This study was also supported by Ticare® implants (Mozo-Grau, Valladolid, Spain). The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication

Effectiveness of Automatic Planning of Fronto-orbital Advancement for the Surgical Correction of Metopic Craniosynostosis

The surgical correction of metopic craniosynostosis usually relies on the subjective judgment of surgeons to determine the configuration of the cranial bone fragments and the degree of overcorrection. This study evaluates the effectiveness of a new approach for automatic planning of fronto-orbital advancement based on statistical shape models and including overcorrection.The authors have no financial interest in relation to the content of this article. This work was supported by grants R42 HD081712 (Eunice Kennedy Shriver National Institute of Child Health and Human Development), K99DE027993 (National Institute of Dental and Craniofacial Research), and PI18/01625 (Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III and European Regional Development Fund “Una manera de hacer Europa”)

Major bleeding predictors in patients with left atrial appendage closure: The iberian registry II

Introduction and objective: Major bleeding events in patients undergoing left atrial appendage closure (LAAC) range from 2.2 to 10.3 per 100 patient-years in di erent series. This study aimed to clarify the bleeding predictive factors that could influence these di erences. Methods: LAAC was performed in 598 patients from the Iberian Registry II (1093 patient-years; median, 75.4 years). We conducted a multivariate analysis to identify predictive risk factors for major bleeding events. The occurrence of thromboembolic and bleeding events was compared to rates expected from CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes, stroke history, vascular disease, sex) and HAS-BLED (hypertension, abnormal renal and liver function, stroke, bleeding, labile INR, elderly, drugs or alcohol) scores. Results: Cox regression analysis revealed that age 75 years (HR: 2.5; 95% CI: 1.3 to 4.8; p = 0.004) and a history of gastrointestinal bleeding (GIB) (HR: 2.1; 95% CI: 1.1 to 3.9; p = 0.020) were two factors independently associated with major bleeding during follow-up. Patients aged <75 or 75 years had median CHA2DS2-VASc scores of 4 (IQR: 2) and 5 (IQR: 2), respectively (p < 0.001) and HAS-BLED scores were 3 (IQR: 1) and 3 (IQR: 1) for each group (p = 0.007). Events presented as follow-up adjusted rates according to age groups were stroke (1.2% vs. 2.9%; HR: 2.4, p = 0.12) and major bleeding (3.7 vs. 9.0 per 100 patient-years; HR: 2.4, p = 0.002). Expected major bleedings according to HAS-BLED scores were 6.2% vs. 6.6%, respectively. In patients with GIB history, major bleeding events were 6.1% patient-years (HAS-BLED score was 3.8 1.1) compared to 2.7% patients-year in patients with no previous GIB history (HAS-BLED score was 3.4 1.2; p = 0.029). Conclusions: In this high-risk population, GIB history and age 75 years are the main predictors of major bleeding events after LAAC, especially during the first year. Age seems to have a greater influence on major bleeding events than on thromboembolic risk in these patient

High-resolution hepatitis C virus subtyping using NS5B deep sequencing and phylogeny, an alternative to current methods

HepatitisCvirus(HCV)is classified into seven major genotypesand67 subtypes. Recent studies haveshownthat inHCVgenotype 1-infected patients, response rates to regimens containingdirect-acting antivirals(DAAs)are subtype dependent. Currently available genotypingmethods have limited subtyping accuracy.Wehave evaluated theperformanceof adeep-sequencing-basedHCVsubtyping assay, developed for the 454/GS-Junior platform, in comparisonwith thoseof two commercial assays (VersantHCVgenotype 2.0andAbbott Real-timeHCVGenotype II)andusingdirectNS5Bsequencing as a gold standard (direct sequencing), in 114 clinical specimenspreviously tested by first-generation hybridization assay (82 genotype 1and32 with uninterpretable results). Phylogenetic analysis of deep-sequencing reads matched subtype 1 callingbypopulation Sanger sequencing(69%1b,31%1a) in 81 specimensandidentified amixed-subtype infection (1b/3a/1a) in one sample. Similarly,amongthe 32previously indeterminate specimens, identical genotypeandsubtype results were obtained by directanddeep sequencing in all but four samples with dual infection. In contrast, both VersantHCVGenotype 2.0andAbbott Real-timeHCVGenotype II failed subtype 1 calling in 13 (16%) samples eachandwere unable to identify theHCVgenotype and/or subtype inmore than half of the nongenotype 1 samples.Weconcluded that deep sequencing ismore efficient forHCVsubtyping than currently available methodsandallows qualitative identificationofmixed infectionsandmay bemorehelpfulwith respect to informing treatment strategies withnewDAA-containing regimens across allHCVsubtypesThis study has been supported by CDTI (Centro para el Desarrollo Tecnológico Industrial), Spanish Ministry of Economics and Competitiveness (MINECO), IDI-20110115; MINECO projects SAF 2009-10403; and also by the Spanish Ministry of Health, Instituto de Salud Carlos III (FIS) projects PI10/01505, PI12/01893, and PI13/00456. CIBERehd is funded by the Instituto de Salud Carlos III, Madrid, Spain. Work at CBMSO was supported by grant MINECO-BFU2011-23604, FIPSE, and Fundación Ramón Areces. X. Forns received unrestricted grant support from Roche and has acted as advisor for MSD, Gilead, and Abbvie. M. Alvarez-Tejado, J. Gregori, and J. M. Muñoz work in Roche Diagnostic

Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Agencia Española del Medicamento; Consejería de Salud de Andalucía.Background & Aims: Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period. Methods: Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected. Results: A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974-0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994-0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy's law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%). Conclusions: AST elevation at onset is a strong predictor of poor outcome and should be routinely assessed in DILI evaluation. Mortality is higher in older patients with hepatocellular damage and patients with underlying hepatic conditions. The Spanish DILI Registry is a valuable tool in the identification of causative drugs, clinical signatures and prognostic risk factors in DILI and can aid physicians in DILI characterisation and management. Lay summary: Clinical information on drug-induced liver injury (DILI) collected from enrolled patients in the Spanish DILI Registry can guide physicians in the decision-making process. We have found that older patients with hepatocellular type liver injury and patients with additional liver conditions are at a higher risk of mortality. The type of liver injury, patient sex and analytical values of aspartate aminotransferase and total bilirubin can also help predict clinical outcomes