Colchicine in acute heart failure: Rationale and design of a randomized double-blind placebo-controlled trial (COLICA).

AIMS: Heart failure (HF) elicits a pro-inflammatory state, which is associated with impaired clinical outcomes, but no anti-inflammatory therapies have demonstrated a clinical benefit yet. Inflammatory pathways related with the interleukin-1 axis are overactivated during episodes of acute HF. Colchicine, an anti-inflammatory drug with proven benefits in acute pericarditis and ischaemic heart disease, may target this inflammatory response. This study aims to assess the efficacy of colchicine in acute HF patients. METHODS: COLICA is a multicentre, randomized, double-blind, placebo-controlled trial enrolling 278 patients across 12 sites. Patients presenting with acute HF, clinical evidence of congestion requiring ≥40 mg of intravenous furosemide and N-terminal pro-B-type natriuretic peptide (NT-proBNP) >900 pg/ml, are eligible for participation. Patients are enrolled irrespective of left ventricular ejection fraction, HF type (new-onset or not) and setting (hospital or outpatient clinic). Patients are randomized 1:1 within the first 24 h of presentation to either placebo or colchicine, with an initial loading dose of 2 mg followed by 0.5 mg every 12 h for 8 weeks (reduced dose if <70 kg, >75 years old, or glomerular filtration rate <50 ml/min/1.73 m2). The primary efficacy endpoint is the time-averaged proportional change in NT-proBNP concentrations from baseline to week 8. Key secondary and exploratory outcomes include symptoms, diuretic use, worsening HF episodes, related biomarkers of cardiac stress and inflammation, total and cardiovascular readmissions, mortality and safety events. CONCLUSION: COLICA will be the first randomized trial testing the efficacy and safety of colchicine for acute HF.

In Vitro Comparison of Internal and Marginal Adaptation between Printed and Milled Onlays.

STATEMENT OF PROBLEM: Nowadays, milling is still the gold standard for fabricating indirect restorations, but to overcome its disadvantages, there are alternatives, such as 3D printing. PURPOSE: This study aimed to compare the gaps between the prepared tooth and milled and printed onlays fabricated with the same CAD design. It also aimed to determine the gap reproducibility across onlays fabricated by 3D printing and milling. METHODS: A resin tooth was prepared for an onlay. After scanning the preparation, an onlay was designed with proprietary dental software. Next, 22 onlays were milled in a graphene-reinforced PMMA disc (Group 1), and 22 onlays were 3D-printed with a hybrid composite material (Group 2). After that, all fabricated restorations were scanned and superimposed on the scanned prepared resin tooth. Subsequently, a specific software was used to measure the margin, central, and intaglio-located gap between the milled or printed restoration and the preparation. Finally, measurements were compared with a multifactor analysis of variance. RESULTS: The results demonstrated that printed onlays (Group 2) adapted better to the prepared tooth than the milled ones (Group 1) (p < 0.05). The comparison of standard deviations showed the better gap reproducibility of printed onlays (p < 0.05). CONCLUSION: This study concluded that the printed onlays adapted significantly better to the prepared tooth than the milled onlays. Printed onlays also showed significantly better gap reproducibility.

Peritoneal and Urinary Sodium Removal in Refractory Congestive Heart Failure Patients Included in an Ambulatory Peritoneal Dialysis Program: Valuable for Monitoring the Course of the Disease.

INTRODUCTION: Spot urinary sodium emerged as a useful parameter for assessing decongestion in patients with congestive heart failure (CHF). Growing evidence endorses the therapeutic role of continuous ambulatory peritoneal dialysis (CAPD) in patients with refractory CHF and kidney disease. We aimed to examine the long-term trajectory of urinary, peritoneal, and total (urinary plus peritoneal) sodium removal in a cohort of patients with refractory CHF enrolled in a CAPD program. Additionally, we explored whether sodium removal was associated with the risk of long-term mortality and episodes of worsening heart failure (WHF). METHODS: We included 66 ambulatory patients with refractory CHF enrolled in a CAPD program in a single teaching center. 24-h peritoneal, urinary, and total sodium elimination were analyzed at baseline and after CAPD initiation. Its trajectories over time were calculated using joint modeling of longitudinal and survival data. Within the framework of joint frailty models for recurrent and terminal events, we estimated its prognostic effect on recurrent episodes of WHF. RESULTS: At the time of enrollment, the mean age and estimated glomerular filtration rate were 72.8 ± 8.4 years and 28.5 ± 14.3 mL/min/1.73 m2, respectively. The median urinary sodium at baseline was 2.34 g/day (1.40-3.55). At a median (p25%-p75%) follow-up of 2.93 (1.93-3.72) years, we registered 0.28 deaths and 0.24 episodes of WHF per 1 person-year. Compared to baseline (urinary), CAPD led to increased sodium excretion (urinary plus dialyzed) since the first follow-up visit (p < 0.001). Over the follow-up, repeated measurements of total sodium removal were associated with a lower risk of death and episodes of WHF. CONCLUSIONS: CAPD increased sodium removal in patients with refractory CHF. Elevated sodium removal identified those patients with a lower risk of death and episodes of WHF.

Early glomerular filtration rates changes and risk of mortality in acute heart failure. The modifying role of admission renal function and decongestion.

BACKGROUND: The pathophysiology of changes in estimated glomerular filtration rate (eGFR) in acute heart failure (AHF) is complex and multifactorial. We evaluated the associated mortality risk of early changes in eGFR across baseline renal function on admission and early changes in natriuretic peptides in patients admitted with AHF. METHODS: We retrospectively evaluated 2,070 patients admitted with AHF. Renal dysfunction on admission was defined as eGFR<60 ml/min/1.73m2 and successful decongestion as NT-proBNP decreased >30% from baseline. We assessed the mortality risk associated with eGFR changes from baseline at 48-72 h after admission (ΔeGFR%) according to baseline renal function, and NT-proBNP changes at 48-72 h through Cox regression analyses. RESULTS: The mean age was 74.4 ± 11.2 years, and 930 (44.9%) were women. The proportion of admission eGFR<60 ml/min/1.73m2 and 48-72 h changes in NT-proBNP>30% were 50.5% and 32.8%, respectively. At a median follow-up of 1.75 years, 928 deaths were registered. In the whole sample, changes in renal function were not associated with mortality (p = 0.208). The adjusted analysis revealed that the risk of mortality related to ΔeGFR% was heterogeneous across baseline renal function and changes in NT-proBNP (p-value for interaction=0.003). ΔeGFR% was not associated with mortality in patients with baseline eGFR≥60 ml/min/1.73m2. In those with eGFR<60 ml/min/1.73m2, a decrease in eGFR was associated with higher mortality, particularly in those with a reduction in NT-proBNP<30%. CONCLUSION: In patients with AHF, early ΔeGFR% was associated with the risk of long-term mortality only in patients with renal dysfunction on admission and no early decline in NT-proBNP.

Narrow diameter titanium-zirconium tissue-level implants supporting multi-unit FDPs in the anterior area: A 5-year prospective study.

BACKGROUND: Narrow diameter implants (NDIs) are used in cases of limited mesio-distal space, or if the alveolar ridge does not allow placement of a standard diameter implant. PURPOSE: The aim of this prospective case series study is to present the 5-year clinical-, radiological-, and patient-reported outcome measures (PROMs) of patients with partial edentulism in the anterior area of the jaws requiring the placement of two narrow diameter implants to support a 3- or 4-unit fixed partial denture (FPD). MATERIALS AND METHODS: Thirty partially edentulous patients missing 3 or 4 adjacent teeth in the anterior area of the jaws were included in the study. Two titanium-zirconium tissue-level NDIs were placed in each patient in healed anterior sites (60 implants). A conventional loading protocol was performed to provide a FPD. Implant survival, success, marginal bone-level changes (MBL), clinical parameters, buccal bone stability with CBCT, adverse events and PROMs were recorded. RESULTS: The survival and success rates for the implants were 100%. The mean MBL (±SD) after prosthesis delivery, and 5-year follow-up (mean 58.8 months; range: 36-60) was 0.12 ± 0.22 and 0.52 ± 0.46 mm, respectively. Decementation and screw loosening were the most frequent prosthetic complications, yielding a prosthetic survival and success rates of 100% and 80%, respectively. Patient satisfaction was high with a mean (±SD) score of 89.6 ± 15.1. CONCLUSIONS: The use of tissue-level titanium-zirconium NDIs supporting splinted multi-unit FPDs in the anterior area seems to be a safe and predictable treatment option after a 5-year follow-up period.

An update on utilising brain natriuretic peptide for risk stratification, monitoring and guiding therapy in heart failure.

INTRODUCTION: Heart failure (HF) is a dominant health problem with an overall poor prognosis. Natriuretic peptides (NPs) are upregulated in HF as a compensatory mechanism. They have been extensively used for diagnosis and risk stratification. AREAS COVERED: This review addresses the history and physiology of NPs in order to understand their current role in clinical practice. It further provides a detailed and updated narrative review on the utility of those biomarkers for risk stratification, monitoring, and guiding therapy in HF. EXPERT OPINION: NPs show excellent predictive ability in heart failure patients, both in acute and chronic settings. Understanding their pathophysiology and their modifications in specific situations is key for an adequate interpretation in specific clinical scenarios in which their prognostic value may be weaker or less well evaluated. To better promote risk stratification in HF, NPs should be integrated with other predictive tools to develop multiparametric risk models. Both inequalities of access to NPs and evidence caveats and limitations will need to be addressed by future research in the coming years.

Short-term Changes in Hemoglobin and Changes in Functional Status, Quality of Life and Natriuretic Peptides After Initiation of Dapagliflozin in Heart Failure With Reduced Ejection Fraction.

BACKGROUND: We aimed to evaluate the effect of dapagliflozin on short-term changes in hemoglobin in patients with stable heart failure with reduced ejection fraction (HFrEF) and whether these changes mediated the effect of dapagliflozin on functional capacity, quality of life and NT-proBNP levels. METHODS: This is an exploratory analysis of a randomized, double-blinded clinical trial in which 90 stable patients with HFrEF were randomly allocated to dapagliflozin or placebo to evaluate short-term changes in peak oxygen consumption (peak VO2) (NCT04197635). This substudy evaluated 1- and 3-month changes in hemoglobin levels and whether these changes mediated the effects of dapagliflozin on peak VO2, Minnesota Living-With-Heart-Failure test (MLHFQ) and NT-proBNP levels. RESULTS: At baseline, mean hemoglobin levels were 14.3 ± 1.7 g/dL. Hemoglobin levels significantly increased in those taking dapagliflozin (1 month: + 0.45 g/dL (P = 0.037) and 3 months:+ 0.55 g/dL (P = 0.012)]. Changes in hemoglobin levels positively mediated the changes in peak VO2 at 3 months (59.5%; P < 0.001). Changes in hemoglobin levels significantly mediated the effect of dapagliflozin in the MLHFQ at 3 months (-53.2% and -48.7%; P = 0.017) and NT-proBNP levels at 1 and 3 months (-68.0%; P = 0.048 and -62.7%; P = 0.029, respectively). CONCLUSIONS: In patients with stable HFrEF, dapagliflozin caused a short-term increase in hemoglobin levels, identifying patients with greater improvements in maximal functional capacity, quality of life and reduction of NT-proBNP levels.

Fracture Resistance in Non-Vital Teeth: Absence of Interproximal Ferrule and Influence of Preparation Depth in CAD/CAM Endocrown Overlays-An In Vitro Study.

There is ample evidence to support the use of endocrowns to restore endodontic teeth. However, the influence of the position of the interproximal margins on fracture strength has not yet been studied. The aim was to determine the relationship between the apicocoronal position of the interproximal restorative margins and fracture resistance in nonvital teeth restored with CAD/CAM endocrown overlays. Forty extracted human maxillary premolars were prepared for endocrown overlay restorations without ferrule on the interproximal aspects and classified according to the position of the interproximal restoration margins in relation to the alveolar crest: 2 mm (group A), 1 mm (group B), 0.5 mm (group C), and 0 mm (group D). Fracture strength was measured using a universal testing machine applying a compressive force to the longitudinal tooth axis. Group A had a mean fracture resistance of 859.61 (±267.951) N, group B 1053.9 (±333.985) N, group C 1124.6 (±291.172) N, and group D 780.67 (±183.269) N, with statistical differences between groups. Group C had the highest values for fracture strength compared to the other groups (p < 0.05). The location of the interproximal margins appears to influence the fracture resistance of CAD/CAM endocrown overlays. A distance of 0.5 mm between the interproximal margin and the alveolar crest was associated with increased fracture resistance.

Fast Identification and Quantification of Uropathogenic E. coli through Cluster Analysis.

Rapid diagnostic tools to detect, identify, and enumerate bacteria are key to maintaining effective antibiotic stewardship and avoiding the unnecessary prescription of broad-spectrum agents. In this study, a 15 min agglutination assay is developed that relies on the use of mannose-functionalized polymeric microspheres in combination with cluster analysis. This allows for the identification and enumeration of laboratory (BW25113), clinical isolate (NCTC 12241), and uropathogenic Escherichia coli strains (NCTC 9001, NCTC 13958, J96, and CFT073) at clinically relevant concentrations in tryptic soy broth (103-108 CFU/mL) and in urine (105-108 CFU/mL). This fast, simple, and efficient assay offers a step forward toward efficient point-of-care diagnostics for common urinary tract infections.

Fracture Resistance of Two Different Composite Resin CAD/CAM Crowns Bonded to Titanium Abutments.

PURPOSE: To determine the influence of thermal and mechanical cycling on fracture load and fracture pattern of resin nanoceramic crowns and polymer-infiltrated ceramic-network (PICN) crowns, both fabricated with CAD/CAM technology. MATERIALS AND METHODS: A total of 90 premolar crowns bonded to titanium abutments were divided into three groups of 30 crowns each: 30 resin nanoceramic crowns (LU); 30 PICN crowns (VE); and 30 metal-ceramic crowns (MC). The 30 specimens of each group were further divided into three subgroups of 10 each that underwent (1) no treatment, (2) thermocycling (2,000 cycles, 5°C to 55°C), and (3) thermocycling with subsequent mechanical cycling (120,000 cycles, 80 N, 2 Hz). The specimens were loaded to failure, and two-way ANOVA and chi-square test were used to determine differences in fracture resistance and pattern. RESULTS: Mechanical and thermal cycling significantly influenced the critical load to failure of the three materials; however, no significant differences were observed between the thermocycled materials and the materials that were thermocycled with subsequent mechanical cycling. The MC specimens experienced significantly higher fracture loads than those of the LU and VE specimens, which showed no differences from each other in fracture resistance. The fracture patterns showed chipping in MC crowns and partial or complete fracture in LU and VE crowns. The fracture pattern depended on the material and was unrelated to the type of treatment it underwent. CONCLUSION: All crowns showed adequate resistance to normal masticatory forces in the premolar area. The cyclic fatigue load negatively influenced all three materials.

BALB/c Mice resist infection with Bartonella bacilliformis.

BACKGROUND: Bartonellosis due to Bartonella bacilliformis is a highly lethal endemic and sometimes epidemic infectious disease in South America, and a serious public health concern in Perú. There is limited information on the immunologic response to B. bacilliformis infection. The objective of this research was to produce experimental infection of BALB/c mice to B. bacilliformis inoculation. FINDINGS: BALB/c mice were inoculated with 1.5, 3.0 or 4.5 x 108 live B. bacilliformis using different routes: intraperitoneal, intradermal, intranasal, and subcutaneous. Cultures of spleen, liver, and lymph nodes from one to 145 days yielded no cultivable organisms. No organs showed lesions at any time. Previously inoculated mice showed no changes in the reinoculation site. CONCLUSION: Parenteral inoculation of live B. bacilliformis via different infection routes produced no macroscopic or microscopic organ lesions in BALB/c mice. It was not possible to isolate B. bacilliformis using Columbia blood agar from 1 to 15 days after inoculation.