Digital Workflow for Immediate Implant Placement and Chairside Provisionalization in the Esthetic Zone

Introduction: Immediate implant placement and immediate chairside provisionalization in the esthetic zone require meticulous treatment planning. A digital workflow that combines intraoral scans and a cone beam computed tomography scan can be used to visualize the surgical and restorative aspects of the treatment and to plan a prosthetically driven implant position. A digital workflow in implant dentistry enables the prefabrication of an individualized CAD/CAM temporary restoration, based on the planned implant position. This could be a predictable method to deliver a screw-retained temporary restoration, directly after static computer-assisted immediate implant surgery. Interventions. Three patients with a failing tooth in the maxillary esthetic zone were treated with immediate implant placement and chairside provisionalization using this digital workflow. After 3 months, a final restoration was placed. Clinical, radiographic, and patient-reported outcome measures were collected prior to implant treatment, 6 weeks after placing the temporary restoration and then 1 month and 1 year after placing the final restoration. Outcomes. At the 1-year follow-up, healthy soft tissues were observed, and peri-implant bone levels were stable. Patient satisfaction after the treatment was high. Conclusion: The three reported cases demonstrate the potential for predictable immediate implant placement and chairside provisionalization using a digital workflow

Monolithic zirconia single tooth implant-supported restorations with CAD/CAM titanium abutments in the posterior region:A 1-year prospective case series study

PURPOSE: To assess the clinical, radiographic, and patient-reported outcome measures, including the success of screw-retained monolithic zirconia implant-supported restorations with CAD/CAM titanium abutments in the posterior region during a 1-year follow-up. METHODS: In a prospective case series, 50 molar sites in the posterior region of 46 patients with a minimum age of 18 years and sufficient bone volume and anatomical conditions for placing an implant (≥8 mm) and an anatomical restoration were included. Parallel-walled implants with a conical connection were inserted in a two-stage surgical procedure. Implant uncovering and healing abutment placement occurred 12 weeks after insertion. Two weeks after mucosa healing, a screw-retained monolithic zirconia restoration with a CAD/CAM titanium abutment was placed. Clinical, radiographic, and patient-reported outcome measures were collected at baseline before implant placement and then during the 1 month and 1 year follow-ups. RESULTS: At the 1 year follow-up, 49 restorations could be evaluated. The plaque accumulation, presence of calculus, bleeding tendency and peri-implant inflammation indices were low, representing healthy peri-implant conditions. The mean marginal bone level change between the 1 month and the 1 year follow-up was -0.17 ± 0.46 mm. The mean patient satisfaction was high. The restoration success was, according to the modified USPHS criteria, 95.9%. CONCLUSION: Monolithic zirconia implant-supported restorations with CAD/CAM titanium abutments have very good clinical, radiographic and patient-reported outcomes after 1 year in function

International Waters – Delivering Results

This publication is the fourth in a series of knowledge publications prepared by the UNDP-GEF International Waters programme that document and highlight key results and achievements at the project and portfolio level, comprising four ‘signature’ programme areas: Large Marine Ecosystems; Lakes, Rivers and Aquifers; Integrated Water Resources and Coastal Area Management; and Global Programmes. The portfolio continues to make progress in sustaining the world’s most significant shared water systems for the billions of people who depend on these ecosystems for their livelihoods and security

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Determinants of the effect of extracorporeal carbon dioxide removal in the SUPERNOVA trial: implications for trial design

Purpose: To describe the variability and determinants of the effect of extracorporeal CO2 removal (ECCO2R) on tidal volume (Vt), driving pressure (ΔP), and mechanical power (PowerRS) and to determine whether highly responsive patients can be identified for the purpose of predictive enrichment in ECCO2R trial design. Methods: Using data from the SUPERNOVA trial (95 patients with early moderate acute respiratory distress syndrome), the independent effects of alveolar dead space fraction (ADF), respiratory system compliance (Crs), hypoxemia (PaO2/FiO2), and device performance (higher vs lower CO2 extraction) on the magnitude of reduction in Vt, ΔP, and PowerRS permitted by ECCO2R were assessed by linear regression. Predicted and observed changes in ΔP were compared by Bland–Altman analysis. Hypothetical trials of ECCO2R, incorporating predictive enrichment and different target CO2 removal rates, were simulated in the SUPERNOVA study population. Results: Changes in Vt permitted by ECCO2R were independently associated with ADF and device performance but not PaO2/FiO2. Changes in ΔP and PowerRS were independently associated with ADF, Crs, and device performance but not PaO2/FiO2. The change in ΔP predicted from ADF and Crs was moderately correlated with observed change in ΔP (R2 0.32, p < 0.001); limits of agreement between observed and predicted changes in ΔP were ± 3.9 cmH2O. In simulated trials, restricting enrollment to patients with a larger predicted decrease in ΔP enhanced the average reduction in ΔP, increased predicted mortality benefit, and reduced sample size and screening size requirements. The increase in statistical power obtained by restricting enrollment based on predicted ΔP response varied according to device performance as specified by the target CO2 removal rate. Conclusions: The lung-protective benefits of ECCO2R increase with higher alveolar dead space fraction, lower respiratory system compliance, and higher device performance. ADF and Crs, rather than severity of hypoxemia, should be the primary factors determining whether to enroll patients in clinical trials of ECCO2R

Identification of potent and selective glucosylceramide synthase inhibitors from a library of N-alkylated iminosugars

Glucosylceramide synthase (GCS) is an important target for clinical drug development for the treatment of lysosomal storage disorders and a promising target for combating type 2 diabetes. Iminosugars are useful leads for the development of GCS inhibitors; however, the effective iminosugar type GCS inhibitors reported have some unwanted cross-reactivity toward other glyco-processing enzymes. In particular, iminosugar type GCS inhibitors often also inhibit to some extent human acid glucosylceramidase (GBA1) and the nonlysosomal glucosylceramidase (GBA2), the two enzymes known to process glucosylceramide. Of these, GBA1 itself is a potential drug target for the treatment of the lysosomal storage disorder, Gaucher disease, and selective GBA1 inhibitors are sought after as potential chemical chaperones. The physiological importance of GBA2 in glucosylceramide processing in relation to disease states is less clear, and here, selective inhibitors can be of use as chemical knockout entities. In this communication, we report our identification of a highly potent and selective N-alkylated l-ido-configured iminosugar. In particular, the selectivity of 27 for GCS over GBA1 is strikin

Feasibility and safety of extracorporeal CO2 removal to enhance protective ventilation in acute respiratory distress syndrome: the SUPERNOVA study

PurposeWe assessed feasibility and safety of extracorporeal carbon dioxide removal (ECCO2R) to facilitate ultra-protective ventilation (V-T 4mL/kg and P(PLAT)25cmH(2)O) in patients with moderate acute respiratory distress syndrome (ARDS).MethodsProspective multicenter international phase 2 study. Primary endpoint was the proportion of patients achieving ultra-protective ventilation with PaCO2 not increasing more than 20% from baseline, and arterial pH>7.30. Severe adverse events (SAE) and ECCO2R-related adverse events (ECCO2R-AE) were reported to an independent data and safety monitoring board. We used lower CO2 extraction and higher CO2 extraction devices (membrane lung cross-sectional area 0.59 vs. 1.30m(2); flow 300-500mL/min vs. 800-1000mL/min, respectively).ResultsNinety-five patients were enrolled. The proportion of patients who achieved ultra-protective settings by 8h and 24h was 78% (74 out of 95 patients; 95% confidence interval 68-89%) and 82% (78 out of 95 patients; 95% confidence interval 76-88%), respectively. ECCO2R was maintained for 5 [3-8]days. Six SAEs were reported; two of them were attributed to ECCO2R (brain hemorrhage and pneumothorax). ECCO2R-AEs were reported in 39% of the patients. A total of 69 patients (73%) were alive at day 28. Fifty-nine patients (62%) were alive at hospital discharge.ConclusionsUse of ECCO2R to facilitate ultra-protective ventilation was feasible. A randomized clinical trial is required to assess the overall benefits and harms.Clinicaltrials.govNCT0228265

Feasibility and safety of extracorporeal CO2 removal to enhance protective ventilation in acute respiratory distress syndrome: the SUPERNOVA study

We assessed feasibility and safety of extracorporeal carbon dioxide removal (ECCO2R) to facilitate ultra-protective ventilation (VT 4 mL/kg and PPLAT ≤ 25 cmH2O) in patients with moderate acute respiratory distress syndrome (ARDS)