Concern about the survival of microorganisms in deep carious lesions may often lead to unnecessary exposure of the pulp during final excavation. There are reasons, therefore, to initiate systematic studies on the alternative procedure known as stepwise excavation. Clinical evaluation of stepwise excavation was performed on 31 deep carious lesions considered to result in pulp perforation by traditional excavation. This study examines the clinical and microbiological alterations during the final excavation performed during long intervals (6–12 months) after the initial treatment that included peripheral dentine excavation and removal of the central cariogenic biomass and the superficial necrotic dentine. The dentine colour and consistency were assessed by means of standardized scales before application of a Ca(OH)₂ compound and a temporary sealing for 6–12 months. Reassessments were performed before and after final excavation. Microbiological dentine samples were obtained in 19 randomly selected lesions by a sterile bur, transferred to and diluted in reduced transport fluid, and plated on tryptic soy agar. After anaerobic incubation at 37°C for 7 days, total colony-forming units per millilitre were counted from (1) peripheral excavated and hard dentine (control), (2) central demineralized dentine before the final excavation, and (3) central dentine after the final excavation. Six samples of central demineralized dentine were without any cultivable flora increasing to 9 samples after the final excavation. The clinical dentine changes occurring during stepwise excavation were characterized by enhanced hardness of the dentine which was associated with a marked reduction in bacterial growth after the final excavation. Despite the presence of bacteria in the excavated dentine none of the carious lesions resulted in pulp perforation, suggesting that the initial removal of the cariogenic biomass appears to be essential for control of caries progression. Stepwise excavation is not only an appropriate treatment of deep carious lesions but is also considered a suitable model for microbiological studies to determine the bacteria persisting in clinically excavated lesions.

This study examined the cultivable microflora before and after stepwise excavation procedures in deep carious lesions in 9 permanent teeth, categorized according to degrees of proximal surface destruction. The final excavation was performed 4–6 months after the initial treatment, which included peripheral dentine excavation and removal of the central cariogenic biomass and the superficial necrotic dentine. Dentine colour and consistency were assessed by means of standardized scales before the application of a Ca(OH)₂ compound and temporary sealing. Reassessments were performed before and after the final excavation. Microbiological samples of the central demineralized dentine were obtained with a sterile bur before and after the first excavation, as well as before and after the final excavation. After anaerobic cultivation on enriched non–selective tryptic soy agar, 30 colonies from a representative area were identified by standardized biochemical and physiological tests. Before temporary restoration, a yellowish and light brown demineralized soft dentine was typically observed, and gram–positive rods accounted for 70% and lactobacilli for 50% of the total colony–forming units. Lactobacillus casei subsp. rhamnosus and Actinomyces naeslundii dominated the lactobacilli and the other gram–positive rods, respectively. Gram–negative rods were the next most frequent isolates, followed by streptococci, each group accounting for about 20% of the colony–forming units in positive samples. Before the final excavation, which did not cause exposure of the pulp in any of the cases, the retained demineralized dentine had changed into a darker and harder tissue, and the total colony–forming units, as well as the frequency and proportions of lactobacilli were substantially reduced. Gram–negative rods also declined, and the flora was dominated by A. naeslundii and various streptococci. In conclusion, the cultivable flora detected following the treatment interval had declined substantially, and the distribution of bacterial species did not represent a typical cariogenic microbiota of deep lesions, confirming the clinical findings of arrested caries progression.

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Background There are no data on the effect of low‐dose anticoagulation as secondary prophylaxis for venous thromboembolism (VTE) in cancer patients. We assessed the efficacy and safety of low‐dose apixaban for 30 months, after initial 6 months of full‐dose treatment. Methods We included 298 patients with cancer and any type of VTE in a single arm interventional clinical trial. All patients were treated with full‐dose apixaban (5 mg twice daily) for 6 months. Total 196 patients with active cancer after 6 months treatment continued with apixaban 2.5 mg twice daily for another 30 months. The main endpoints were recurrent VTE, major bleeding and clinically relevant non‐major bleeding. Results During the 30 months of treatment with low‐dose apixaban 14 (7.6%; 95% confidence interval (CI) 4.0%–11.7%) patients experienced recurrent VTE, six (3.1%; 95% CI 1.1%–6.5%) experienced major bleeding and 16 (8.1%, 95% CI: 4.7%–12.8%) experienced clinically relevant non‐major bleeding. The incidence rate per person month of recurrent VTE was 0.8% (95% CI 0.41–1.6) at 2–6 months with full‐dose apixaban, and 1.0% (95% CI 0.5–1.9) at 7–12 months with low‐dose apixaban. The incidence rate of major bleeding was 1.1% (95% CI 0.6–2.0) at 2–6 months, and 0.3% (95% CI 0.1–1.0) at 7–12 months. Between 12 and 36 months the incidence rate of recurrent VTE and major bleedings remained low. Conclusion Dose reduction of apixaban to 2.5 mg twice daily seems safe after 6 months of full‐dose treatment. After 12 months the incidence rate of recurrent VTE and major bleeding remained low.

Recent studies have indicated that Treg contribute to the HIV type 1 (HIV‐1)‐related immune pathogenesis. However, it is not clear whether T cells with suppressive properties reside within the HIV‐1‐specific T‐cell population. Here, PBMC from HIV‐1‐infected individuals were stimulated with a 15‐mer Gag peptide pool, and HIV‐1‐specific T cells were enriched by virtue of their secretion of IL‐10 or IFN‐γ using immunomagnetic cell‐sorting. Neither the IL‐10‐secreting cells nor the IFN‐γ‐secreting cells expressed the Treg marker FOXP3, yet the IL‐10‐secreting cells potently suppressed anti‐CD3/CD28‐induced CD4+ as well as CD8+ T‐cell proliferative responses. As shown by intracellular cytokine staining, IL‐10‐ and IFN‐γ‐producing T cells represent distinct subsets of the HIV‐1‐specific T cells. Our data collectively suggest that functionally defined HIV‐1‐specific T‐cell subsets harbor potent immunoregulatory properties that may contribute to HIV‐1‐associated T‐cell dysfunction.