Abstract Introduction The aim of the present study was to systematically analyze the protocols that have been used in regenerative endodontic therapy and to detect any variations in clinical ...procedures. Methods An electronic search was executed in PubMed using appropriate Medical Subject Heading terms covering the period from January 1993 to May 2014. Additional publications from hand searching and the reference section of each relevant article enriched the article list. The relevance of each article was initially evaluated by scanning all titles and corresponding abstracts. The definite inclusion of each article in the study was determined by using specific criteria applied independently by 3 reviewers. Results Sixty relevant publications were finally included. The canal walls were not mechanically instrumented in 68% of the clinical articles. Sodium hypochlorite was included in 97% of the clinical studies either as the only irrigant or in combination with other irrigants. Antibiotic combination paste was used as the intracanal medicament in 80% of the clinical articles. Sodium hypochlorite, chlorhexidine, and EDTA were used in the final irrigation protocol in 75%, 4%, and 13% of the clinical studies, respectively. Neither the creation of a blood clot nor the use of platelet-rich plasma/platelet-rich fibrin was described in 13% of the clinical articles. Mineral trioxide aggregate was used as an intracanal coronal barrier in 85% of the relevant clinical studies. Conclusions The variability of the clinical protocols applied during regenerative enododontic procedures is considerably high. A thorough analysis of regenerative protocols may constitute an additional source to provide useful clinical considerations for REPs.
Despite clear guidelines recommendations, most patients with heart failure and reduced ejection-fraction (HFrEF) do not attain guideline-recommended target doses. We aimed to investigate ...characteristics and for treatment-indication-bias corrected clinical outcome of patients with HFrEF that did not reach recommended treatment doses of ACE-inhibitors/Angiotensin receptor blockers (ARBs) and/or beta-blockers.
BIOSTAT-CHF was specifically designed to study uptitration of ACE-inhibitors/ARBs and/or beta-blockers in 2516 heart failure patients from 69 centres in 11 European countries who were selected if they were suboptimally treated while initiation or uptitration was anticipated and encouraged. Patients who died during the uptitration period (n = 151) and patients with a LVEF > 40% (n = 242) were excluded. Median follow up was 21 months. We studied 2100 HFrEF patients (76% male; mean age 68 ±12), of which 22% achieved the recommended treatment dose for ACE-inhibitor/ARB and 12% of beta-blocker. There were marked differences between European countries. Reaching <50% of the recommended ACE-inhibitor/ARB and beta-blocker dose was associated with an increased risk of death and/or heart failure hospitalization. Patients reaching 50-99% of the recommended ACE-inhibitor/ARB and/or beta-blocker dose had comparable risk of death and/or heart failure hospitalization to those reaching ≥100%. Patients not reaching recommended dose because of symptoms, side effects and non-cardiac organ dysfunction had the highest mortality rate (for ACE-inhibitor/ARB: HR 1.72; 95% CI 1.43-2.01; for beta-blocker: HR 1.70; 95% CI 1.36-2.05).
Patients with HFrEF who were treated with less than 50% of recommended dose of ACE-inhibitors/ARBs and beta-blockers seemed to have a greater risk of death and/or heart failure hospitalization compared with patients reaching ≥100%.
Acute heart failure (AHF) critically deranges haemodynamic and metabolic homoeostasis. Iron is a key micronutrient for homoeostasis maintenance. We hypothesized that iron deficiency (ID) defined as ...depleted iron stores accompanied by unmet cellular iron requirements would in this setting predict the poor outcome.
Among 165 AHF patients (age 65 ± 12 years, 81% men, 31% de novo HF), for ID diagnosis we prospectively applied: low serum hepcidin reflecting depleted iron stores (<14.5 ng/mL, the 5th percentile in healthy peers), and high-serum soluble transferrin receptor (sTfR) reflecting unmet cellular iron requirements (≥1.59 mg/L, the 95th percentile in healthy peers). Concomitance of low hepcidin and high sTfR (the most profound ID) was found in 37%, isolated either high sTfR or low hepcidin was found in 29 and 9% of patients, and 25% of subjects demonstrated preserved iron status. Patients with low hepcidin and high sTfR had peripheral oedema, high NT-proBNP, high uric acid, low haemoglobin (P < 0.05), and 5% in-hospital mortality (0% in remaining patients). During the 12-month follow-up, 33 (20%) patients died. Those with low hepcidin and high sTfR had the highest 12-month mortality (41% (95% CI: 29-53%) when compared with those with isolated high sTfR 15% (5-25%), isolated low hepcidin 7% (0-19%) and preserved iron status (0%) (P < 0.001). Analogous mortality patterns were seen separately in anaemics and non-anaemics.
Iron deficiency defined as depleted body iron stores and unmet cellular iron requirements is common in AHF, and identifies those with the poor outcome. Its correction may be an attractive therapeutic approach.
Abstract Introduction The aim of this systematic review was to assign levels of evidence (LOEs) to existing clinical articles related to the outcome of regenerative endodontic therapy and to evaluate ...the clinical and radiographic outcomes of this treatment modality. Methods Electronic search was executed in PubMed, Scopus, and Cochrane databases by using appropriate Medical Subject Headings terms covering the period from January 1993 to December 2013. Additional publications from hand-searching and reference section of each relevant article enriched the article list. The LOE of each article was assessed according to guidelines provided by the Oxford Centre of Evidence-Based Medicine. Quality assessment of the observational studies was executed by using the Newcastle-Ottawa scale. Results Fifty-one relevant publications were included in this review. There were 2 high-level cohort studies (LOE 2), 8 case series (LOE 4), and 41 case reports (LOE 5). The vast majority of the treated teeth in those publications showed resolution of clinical signs, symptoms, and periapical radiolucencies at follow-up period. Furthermore, the majority of treated teeth presented further increase in root length and root wall thickness and apical closure at the follow-up period. However, because of lack of sufficient high-level evidence it was not possible to answer totally the review question and determine definitely the outcome of regenerative endodontic therapy. Conclusions The lack of adequate high-level studies that could possibly strengthen the satisfactory current data and allow practicing more evidence-based dentistry constitutes a significant knowledge gap in the endodontic literature. However, the current best available evidence undeniably allows clinicians to provide this treatment modality safely to patients.
Background
We aimed to study whether improvement in renal function by serelaxin in patients who were hospitalized for acute heart failure (HF) might explain any potential effect on clinical outcomes.
...Methods
We included 6318 patients from the RELAXin in AHF-2 (RELAX-AHF2) study. Improvement in renal function was defined as a decrease in serum creatinine of ≥ 0.3 mg/dL and ≥ 25%, or increase in estimated glomerular filtration rate of ≥ 25% between baseline and day 2. Worsening renal function (WRF) was defined as the reverse. We performed causal mediation analyses regarding 180-day all-cause mortality (ACM), cardiovascular death (CVD), and hospitalization for HF/renal failure.
Results
Improvement in renal function was more frequently observed with serelaxin when compared with placebo OR 1.88 (95% CI 1.64–2.15,
p
< 0.0001), but was not associated with subsequent clinical outcomes. WRF occurred less frequent with serelaxin OR 0.70 (95% CI 0.60–0.83,
p
< 0.0001) and was associated with increased risk of ACM, worsening HF and the composite of CVD and HF or renal failure hospitalization. Improvement in renal function did not mediate the treatment effect of serelaxin CVD HR 1.01 (0.99–1.04), ACM HR 1.01 (0.99–1.03), HF/renal failure hospitalization HR 0.99 (0.97–1.00).
Conclusions
Despite the significant improvement in renal function by serelaxin in patients with acute HF, the potential beneficial treatment effect was not mediated by improvement in renal function. These data suggest that improvement in renal function might not be a suitable surrogate marker for potential treatment efficacy in future studies with novel relaxin agents in acute HF.
Graphical abstract
Central illustration. Conceptual model explaining mediation analysis; treatment efficacy of heart failure therapies mediated by renal function.
We sought to determine subtypes of patients with heart failure (HF) with a distinct clinical profile and treatment response, using a wide range of biomarkers from various pathophysiological domains.
...We performed unsupervised cluster analysis using 92 established cardiovascular biomarkers to identify mutually exclusive subgroups (endotypes) of 1802 patients with HF and reduced ejection fraction (HFrEF) from the BIOSTAT-CHF project. We validated our findings in an independent cohort of 813 patients. Based on their biomarker profile, six endotypes were identified. Patients with endotype 1 were youngest, less symptomatic, had the lowest N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and lowest risk for all-cause mortality or hospitalization for HF. Patients with endotype 4 had more severe symptoms and signs of HF, higher NT-proBNP levels and were at highest risk for all-cause mortality or hospitalization for HF hazard ratio (HR) 1.4; 95% confidence interval (CI) 1.1-1.8. Patients with endotypes 2, 3, and 5 were better uptitrated to target doses of beta-blockers (P < 0.02 for all). In contrast to other endotypes, patients with endotype 5 derived no potential survival benefit from uptitration of angiotensin-converting enzyme-inhibitor/angiotensin-II receptor blocker and beta-blockers (Pinteraction <0.001). Patients with endotype 2 (HR 1.29; 95% CI 1.10-1.42) experienced possible harm from uptitration of beta-blockers in contrast to patients with endotype 4 and 6 that experienced benefit (Pinteraction for all <0.001). Results were strikingly similar in the independent validation cohort.
Using unsupervised cluster analysis, solely based on biomarker profiles, six distinct endotypes were identified with remarkable differences in characteristics, clinical outcome, and response to uptitration of guideline directed medical therapy.
Abstract Lateral and apical ramifications of the main root canal create potential pathways through which bacteria can spread and remain unaffected by treatment procedures. It is a challenge for the ...specialty to find techniques that can predictably reach, disinfect, and obturate these ramifications. Here, we report the use of a novel instrumentation approach to aid in the negotiation and management of a lateral canal discernible on cone-beam computed tomography (CBCT) in an unusual maxillary central incisor. A 23-year-old female patient was referred for evaluation and possible treatment of tooth 9. The periapical radiographic examination revealed pulp chamber obliteration, existence of a lateral lesion, and a possible complex internal root canal anatomy. The CBCT evaluation revealed the existence of a lateral lesion, a periapical lesion, an additional distopalatal canal, and a lateral canal exiting at the lateral lesion. The diagnosis of asymptomatic apical and lateral periodontitis of tooth 9 was reached. CBCT-aided access cavity preparation and scouting resulted in the successful negotiation of all canals, main and lateral. A novel instrumentation technique with precurved controlled memory files was used for the mechanical preparation of the lateral canal to a 25/04 enlargement. Obturaton of the lateral canal was achieved with a single gutta-percha cone and AH Plus Root Canal Sealer. At the 2-year follow-up, the patient was asymptomatic, and the 2-dimensional radiographic examinations revealed resolution of both the periapical and the lateral lesions. This case report describes the application of a novel instrumentation technique for the mechanical debridement of an infected lateral canal discernible on CBCT and reinforces the importance of treating the root canals as systems that possesses anatomic intricacies that need to be addressed.
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