Remineralization of artificially demineralized dentin in vitro

Objectives: Based on new concepts on the pathogenesis of dental caries, the management of carious lesions in proximity to the dental pulp has been largely changed. Ultraconservative excavation or removal is usually advised to avoid pulpal damage. The remaining demineralized tissue near the pulp, however, comes with challenges. One such challenge is to remineralize the residual lesion, for example using lining or restorative materials. In the present study, we tried to compare the remineralization activity of two different materials, calcium hydroxide and glass hybrid, on artificial residual lesions, in a pulpal fluid simulation system in vitro. Methods: On human dentin discs (n=20), artificial residual lesions (median mineral loss ΔZ [25th/75th percentiles]=1643 [1301/1858] vol%×µm) were chemically induced using demineralization solution without bacterial invasion. The dentin discs were divided into five parts, one of them served as baseline sample. The remaining four parts were used as experimental groups, with each being covered with a different material or material combination (n=20/group): Flowable composite (CO) without liner (control), setting and non-setting calcium hydroxide covered with flowable composite (CH-S, CH-NS), glass hybrid (GH). Samples were mounted in a dual-chamber device allowing pulpal fluid simulation. Pulpal surfaces were subjected to simulated pulpal fluid at 2.94 kPa, while coronal surfaces were exposed to artificial saliva, and once weekly rinsed with 200 ppm NaF. Solutions were changed regularly every 14 day. After 12 weeks, mineral loss differences compared to baseline were evaluated using transversal microradiography. Fluoride and strontium concentrations in exemplary samples were analyzed using Field Emission Electron Probe Micro-Analyzer (FE-EPMA). Results: Mineral gain in CO (negative control) was ΔΔZ=372 (115/501) vol%×µm. This was not significantly different from CH-S (ΔΔZ=317 [229/919] vol%×µm) or CH-NS (ΔΔZ=292 [130/579] vol%×µm), (p>0.05/Wilcoxon-test), but while mineral gain was significantly higher in GH (ΔΔZ=1044 [751/1264] vol%×µm, p<0.001). GH samples showed fluoride and strontium enrichments deep into the dentin. Such enrichment was not found in CO or CH samples. Conclusion: Within the limitations of this study, glass hybrid, but not calcium hydroxide provided coronal remineralization of residual carious lesions. Clinical relevance: Glass hybrids might provide additional remineralization of residual carious lesions.Ziel: Basierend auf neuen Konzepten zur Pathogenese der Dentalkaries hat sich das Management kariöser Läsionen in der Nähe der Zahnpulpa weitgehend geändert. In der Regel wird zu einer ultrakonservativen Exkavation oder Entfernung geraten, um Schäden an der Pulpa zu vermeiden. Das verbleibende demineralisierte Gewebe in der Nähe der Pulpa bringt jedoch Herausforderungen mit sich, u.a. die Remineralisierung der verbleibenden Läsion, zum Beispiel durch Liner- oder Restaurationsmaterialien. In der vorliegenden Studie haben wir die Remineralisierungsaktivität zwei verschiedener Materialien, Calciumhydroxid und Glashybrid, auf künstlichen Residualläsionen in vitro verglichen. Methoden: Auf humanen Dentinscheiben (n=20) wurden künstliche Residualläsionen (medianer Mineralverlust ΔZ [25./75. Perzentile] =1643 [1301/1858] Vol.%×µm) chemisch induziert. Die Dentinscheiben wurden in fünf Teile geteilt, von denen einer als Ausgangsprobe diente. Die restlichen vier Teile dienten als Versuchsgruppen, wobei jede mit einem anderen Material oder einer anderen Materialkombination beschichtet wurde (n=20/Gruppe): Fließfähiges Komposit (CO) ohne Liner (Kontrolle), abbindendes und nicht abbindendes Kalziumhydroxid, bedeckt mit fließfähigem Komposit (CH-S, CH-NS), Glashybrid (GH). Die Proben wurden in einem Zweikammergerät montiert, das eine Simulation von Pulpaflüssigkeit ermöglichte. Die Pulpaoberflächen wurden der simulierten Pulpaflüssigkeit bei 2,94 kPa ausgesetzt, während die koronalen Oberflächen einem künstlichen Speichel ausgesetzt und einmal wöchentlich mit 200 ppm NaF gespült wurden. Die Lösungen wurden regelmäßig alle 14 Tage gewechselt. Nach 12 Wochen wurden die Unterschiede im Mineralverlust im Vergleich zur Ausgangsprobe mittels transversaler Mikroradiographie ausgewertet. Die Fluorid- und Strontiumkonzentrationen in exemplarischen Proben wurden mittels Field Emission Electron Probe Micro-Analyzer (FE-EPMA) analysiert. Ergebnisse: Der Mineralgewinn in CO (Negativkontrolle) betrug ΔΔZ=372 (115/501) Vol.%×µm, dies war nicht signifikant unterschiedlich zu CH-S (ΔΔZ=317 [229/919] Vol.%×µm) oder CH-NS (ΔΔZ=292 [130/579] Vol.%×µm), (p>0.05/Wilcoxon-Test), aber während der Mineralgewinn in GH signifikant höher war (ΔΔZ=1044 [751/1264] Vol.%×µm, p<0.001). GH-Proben zeigten Fluorid- und Strontiumanreicherungen tief im Dentin. Eine solche Anreicherung wurde in CO- oder CH-Proben nicht gefunden. Schlussfolgerung: Innerhalb der Grenzen dieser Studie bewirkte Glashybrid, nicht aber Calciumhydroxid, eine koronale Remineralisierung von kariösen Residualläsionen. Klinische Relevanz: Glashybride könnten eine zusätzliche Remineralisierung von kariösen Residualläsionen bewirken

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

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

Secondary Caries Adjacent to Bulk or Incrementally Filled Composites Placed after Selective Excavation In Vitro

Objectives: selective caries excavation (SE) is recommended for deep carious lesions. Bulk fill composites (BF) may be considered to restore SE-cavities. We compared the susceptibility for secondary caries adjacent to BF versus incrementally filled composites (IF) in SE and non-selectively excavated teeth (NS) in vitro. Methods: in 72 extracted human premolars, artificial caries lesions were induced on pulpo-axial walls of standardized cavities. The lesions were left (SE) or removed (NS), and teeth were restored using two BF, GrandioSO x-tra/Voco (BF-Gra) and SDR/Dentsply (BF-SDR), and an IF, GrandioSO/Voco (IF-Gra) (n = 12/group for SE and NS). After thermo-mechanical cycling (5-55 °C, 8 days), teeth were submitted to a continuous-culture Lactobacillus rhamnosus biofilm model with cyclic loading for 10 days. Mineral loss (ΔZ) of enamel surface lesions (ESL), dentin surface lesions (DSL), and dentin wall lesions (DWL) was analyzed using transversal microradiography. Results: ΔZ was the highest in DSL, followed by ESL, and it was significantly lower in DWL. There were no significant differences in ΔZ between groups in DSL, ESL, and DWL (p > 0.05). Regardless of lesion location, ΔZ did not differ between SE and NS (p > 0.05). Conclusions: BF and IF both showed low risks for DWL (i.e., true secondary caries) after SE in vitro, and surface lesion risk was also not significantly different between materials. SE did not increase secondary caries risk as compared with NS. Clinical Significance: the risk of secondary caries was low after selective excavation in this study, regardless of whether bulk or incrementally filled composites were use

Secondary Caries Adjacent to Bulk or Incrementally Filled Composites Placed after Selective Excavation In Vitro

Objectives: selective caries excavation (SE) is recommended for deep carious lesions. Bulk fill composites (BF) may be considered to restore SE-cavities. We compared the susceptibility for secondary caries adjacent to BF versus incrementally filled composites (IF) in SE and non-selectively excavated teeth (NS) in vitro. Methods: in 72 extracted human premolars, artificial caries lesions were induced on pulpo-axial walls of standardized cavities. The lesions were left (SE) or removed (NS), and teeth were restored using two BF, GrandioSO x-tra/Voco (BF-Gra) and SDR/Dentsply (BF-SDR), and an IF, GrandioSO/Voco (IF-Gra) (n = 12/group for SE and NS). After thermo-mechanical cycling (5–55 °C, 8 days), teeth were submitted to a continuous-culture Lactobacillus rhamnosus biofilm model with cyclic loading for 10 days. Mineral loss (ΔZ) of enamel surface lesions (ESL), dentin surface lesions (DSL), and dentin wall lesions (DWL) was analyzed using transversal microradiography. Results: ΔZ was the highest in DSL, followed by ESL, and it was significantly lower in DWL. There were no significant differences in ΔZ between groups in DSL, ESL, and DWL (p &gt; 0.05). Regardless of lesion location, ΔZ did not differ between SE and NS (p &gt; 0.05). Conclusions: BF and IF both showed low risks for DWL (i.e., true secondary caries) after SE in vitro, and surface lesion risk was also not significantly different between materials. SE did not increase secondary caries risk as compared with NS. Clinical Significance: the risk of secondary caries was low after selective excavation in this study, regardless of whether bulk or incrementally filled composites were use

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc