Problems in the “Evidence” of “Evidence-Based Medicine”

The proposed practice of “evidence-based medicine,” which calls for careful clinical judgment in evaluating the “best available evidence,” should be differentiated from the special collection of data regarded as suitable evidence. Although the proposed practice does not seem new, the new collection of “best available” information has major constraints for the care of individual patients.Derived almost exclusively from randomized trials and meta-analyses, the data do not include many types of treatments or patients seen in clinical practice; and the results show comparative efficacy of treatment for an “average” randomized patient, not for pertinent subgroups formed by such cogent clinical features as severity of symptoms, illness, co-morbidity, and other clinical nuances. The intention-to-treat analyses do not reflect important post-randomization events leading to altered treatment; and the results seldom provide suitable background data when therapy is given prophylactically rather than remedially, or when therapeutic advantages are equivocal. Randomized trial information is also seldom available for issues in etiology, diagnosis, and prognosis, and for clinical decisions that depend on pathophysiologic changes, psychosocial factors and support, personal preferences of patients, and strategies for giving comfort and reassurance.The laudable goal of making clinical decisions based on evidence can be impaired by the restricted quality and scope of what is collected as “best available evidence.” The authoritative aura given to the collection, however, may lead to major abuses that produce inappropriate guidelines or doctrinaire dogmas for clinical practice.     

Catheterization in Adults With Congenital Heart Disease: A Primer for the Noncongenital Proceduralist

Currently in the United States, more than 1 million adults have congenital heart disease. Therefore, it will be inevitable for providers performing cardiac catheterization to be faced with adults with repaired congenital heart abnormalities. Moreover, a meticulous approach to every cardiac catheterization procedure is mandatory to avoid missing unrecognized congenital lesions presenting in adulthood. The authors provide a primer for cardiac catheterization procedures in adults with congenital heart disease, reviewing key procedural components: flow calculation, detection of shunts according to different lesions, and, when indicated, ventricular angiography and coronary angiography.     

Why and How to Measure Aortic Valve Calcification in Patients With Aortic Stenosis

The first-line evaluation of aortic stenosis severity is Doppler echocardiography. However, in up to 40% of patients, resting echocardiographic assessment of aortic stenosis severity is discordant, leading to clinical uncertainty. Interest has therefore grown in aortic valve calcium scoring by multidetector computed tomography (CT-AVC) as an alternative load independent assessment of aortic stenosis severity. This paper will briefly review the pathophysiology of aortic stenosis and the crucial role that calcification plays in driving progressive obstruction of the valve. Subsequently, it will describe published reports that have investigated CT-AVC, validating this parameter against histology, and establishing its diagnostic accuracy versus echocardiography as well as its powerful independent prognostic capability. Finally, this review seeks to provide a practical guide about how best to acquire and interpret CT-AVC with a close focus on potential pitfalls and how these might be best avoided as this technique becomes more widely adopted in to clinical practice.     

Occurence of <Emphasis Type="Italic">Echinococcus multilocularis</Emphasis> in red foxes (<Emphasis Type="Italic">Vulpes vulpes</Emphasis>) in southern Poland

Summary The prevalence of Echinococcus multilocularis in 214 red foxes (Vulpes vulpes) in the southern part of Poland (Małopolskie voivodship) was evaluated post mortem in 2005. Infected foxes were found in 8 districts within 17 examined, with the prevalence from 10.0 % to 63.9 % (a mean 20.1 % in the whole study area). The highest prevalence (41.2 % and 63.9 %) was revealed in two districts, in the south and the east of the province, respectively. The high prevalence of E. multilocularis in red foxes in the region previously recognised as that of low parasite endemicity provides evidence for the need of regular screening of the current epidemiological situation in foxes as well as the monitoring of humans from risk groups for early recognition of possible AE cases.     

Ageing in nematodes: do antioxidants extend lifespan in <Emphasis Type="Italic">Caenorhabditis</Emphasis><Emphasis Type="Italic">elegans</Emphasis>?

Antioxidants are often investigated as a promising strategy for extending lifespan. Accordingly, there is significant interest in novel antioxidant compounds derived from natural sources such as plant extracts. However, because lifespan studies are laborious and expensive to conduct, candidate compounds are frequently selected based simply on their in vitro antioxidant efficacy, with the implicit assumption that in vitro antioxidants are also in vivo antioxidants, and that in vivo antioxidants will decrease functionally relevant oxidative damage and thereby extend lifespan. We investigated the validity of these assumptions in the model organism, Caenorhabditis elegans. Nematodes were exposed to 6 plant extracts, selected out of a total of 34 based on a simple in vitro antioxidant assay. We found no correlation between in vitro and in vivo antioxidant capacities. Antioxidant efficacies were also not predictive of lifespan benefits. Further studies into those extracts that produced significant lifespan extension indicated that a direct antioxidant effect is unlikely to be the main factor responsible for the modulation of nematode lifespan.     

L’hormone antimüllérienne sérique n’est pas prédictive de la qualité ovocytaire en fécondation in vitro

Objectives

The assessment of the ovarian reserve is mandatory in women undergoing assisted reproduction. Anti-Müllerian hormone (AMH), produced by granulosa cells from pre-antral and early antral follicles, is a promising indicator of ovarian reserve. However, few studies have evaluated the predictive value of AMH on oocyte quality.

Patients and methods

A retrospective study was undertaken at the Bretonneau University Hospital of Tours. A total of 559 women undergoing in vitro fertilization treatment between January and December 2007 were included in the study. Serum AMH levels were determined by using an ultrasensitive Elisa test. Total number of oocytes, rate of mature oocytes, fertilization rate, embryo quality and clinical pregnancy rate were recorded.

Results

Serum AMH was significantly lower in groups of patients with few oocytes collected. However, serum AMH was not predictive of nuclear maturity of oocytes, fertilization rate and quality of early embryos. Additionally, low levels of AMH do not preclude clinical pregnancy in in vitro fertilization.

Conclusion

At the moment, serum AMH is a relatively predictive indicator of the ovarian reserve, in terms of quantity but not in terms of quality. Moreover, it is still not possible to determine serum AMH cut-off value to predict clinical pregnancy in IVF programmes.     

Transcatheter Aortic Valve Replacement in Failed Transcatheter Bioprosthetic Valves

Transcatheter aortic valve replacement (TAVR) is increasingly being performed in younger and lower surgical risk patients. Given the longer life expectancy of these patients, the bioprosthetic valve will eventually fail, and aortic valve reintervention may be necessary. Although currently rare, redo-TAVR will likely increase in the future as younger patients are expected to outlive their transcatheter bioprosthesis. This review provides a contemporary overview of the indications, procedural planning, implantation technique, and outcomes of TAVR in failed transcatheter bioprosthetic aortic valves.     

Pulmonary Artery Strain Predicts Prognosis in Pulmonary Arterial Hypertension

BackgroundCurrent cardiac magnetic resonance (CMR) imaging in pulmonary arterial hypertension (PAH) focuses on measures of ventricular function and coupling.ObjectivesThe purpose of this study was to evaluate pulmonary artery (PA) global longitudinal strain (GLS) as a prognostic marker in patients with PAH.MethodsThe authors included 169 patients with PAH from the ASPIRE (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre) and INITIATE (Integrated computatioNal modelIng of righT heart mechanIcs and blood flow dynAmics in congeniTal hEart disease) registries, and 82 normal controls with similar age and gender distributions. PA GLS was derived from CMR feature tracking. Right ventricular measurements including volumes, ejection fraction, and right ventricular GLS were also derived from CMR. Patients were followed up a median of 34 months with all-cause mortality as the primary endpoint. Other known risk scores were collected, including the REVEAL (Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management) 2.0 and COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) 2.0 scores.ResultsOf 169 patients (mean age: 57 ± 15 years; 80% female), 45 (26.6%) died (median follow-up: 34 months). Mean PA GLS was 23% ± 6% in normal controls and 10% ± 5% in patients with PAH (P < 0.0001). Patients with PA GLS <9% had a higher risk of mortality than those with PA GLS ≥9% (P < 0.001), and this was an independent predictor of mortality in PAH on multivariable analysis after adjustment for known risk factors (HR: 2.93; P = 0.010). Finally, in patients with PAH, PA GLS provided incremental prognostic value over the REVEAL 2.0 (global chi-square; P = 0.001; C statistic comparison; P = 0.030) and COMPERA 2.0 (global chi-square; P = 0.001; C statistic comparison; P = 0.048).ConclusionsPA GLS confers incremental prognostic utility over the established risk scores for identifying patients with PAH at higher risk of death, who may be targeted for closer monitoring and/or intensified therapy.     

Use of the Limited Antegrade Subintimal Tracking Technique in Chronic Total Occlusion Percutaneous Coronary Intervention

BackgroundThere are limited data on the limited antegrade subintimal tracking (LAST) technique for chronic total occlusion (CTO) percutaneous coronary intervention (PCI).ObjectivesThe aim of this study was to analyze the frequency of use and outcomes of the LAST technique for CTO PCI.MethodsWe analyzed 2,177 CTO PCIs performed using antegrade dissection and re-entry (ADR) in the PROGRESS-CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) registry between 2012 and January 2022 at 39 centers. ADR was attempted in 1,465 cases (67.3%).ResultsAmong antegrade re-entry cases, LAST was used in 163 (11.1%) (primary LAST in 127 [8.7%] and secondary LAST [LAST after other ADR approaches failed] in 36 [2.5%]), the Stingray system (Boston Scientific) in 980 (66.9%), subintimal tracking and re-entry in 387 (26.4%), and contrast-guided subintimal tracking and re-entry in 29 (2.0%). The mean patient age was 65.2 ± 10 years, and 85.8% were men. There was no significant difference in technical (71.8% vs 77.8%; P = 0.080) and procedural (69.9% vs 75.3%; P = 0.127) success and major cardiac adverse events (1.84% vs 3.53%; P = 0.254) between LAST and non-LAST cases. However, on multivariable analysis, the use of LAST was associated with lower procedural success (OR: 0.61; 95% CI: 0.41-0.91). Primary LAST was associated with higher technical (76.4% vs 55.6%; P = 0.014) and procedural (75.6% vs 50.0%; P = 0.003) success and similar major adverse cardiac event (1.57% vs 2.78%; P = 0.636) rates compared with secondary LAST.ConclusionsLAST was used in 11.1% of antegrade re-entry CTO PCI cases and was associated with lower procedural success on multivariable analysis, suggesting a limited role of LAST in contemporary CTO PCI.     

<Emphasis Type="Italic">Aphanocladium album</Emphasis> by via sub-irrigation in the control of <Emphasis Type="Italic">Pyrenochaeta lycopersici</Emphasis> and <Emphasis Type="Italic">Meloidogyne incognita</Emphasis> on tomato in a plastic-house

Summary  Two experiments were carried out to assess the efficacy of different chemicals (azoxystrobin, fosthiazate, metham-sodium) and of the chitinolytic fungus Aphanocladium album (isolate MX-95), that could be alternatives to methyl bromide, against the soil borne pathogen Pyrenochaeta lycopersici and the root-knot nematode Meloidogyne incognita on tomato in a plastic house in southern Italy. In the first trial, the treatments were azoxystrobin (1.25 l a.i. /ha), fosthiazate (1.5 l a.i. /ha) and biological control agent Aphanocladium album isolate MX-95 (2.5 l/plot at 2×10⁷ CFU/ml; plot surface 96 m²). In the second experiment, treatments were metham-sodium (1000 l c.p./ha) and A. album (5 l/plot at 1×10⁷ CFU/ml). In both trials, chemicals and the fungus were applied by via sub-irrigation. Satisfactory control of the corky root and the root-knot nematode attack and a significant yield increase were obtained by application of azoxystrobin, fosthiazate and metham-sodium. A significant reduction of M. incognita soil population density occurred in plots treated with A. album. Also, high positive correlations were found between the symptoms caused on tomato roots by M. incognita and P. lycopersici.     

Moderate Aortic Stenosis in Patients With Heart Failure and Reduced Ejection Fraction

BackgroundThe study investigators previously reported that moderate aortic stenosis (AS) is associated with a poor prognosis in patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF) (HFrEF). However, the respective contribution of moderate AS versus HFrEF to the outcomes of these patients is unknown.ObjectivesThis study sought to determine the impact of moderate AS on outcomes in patients with HFrEF.MethodsThe study included 262 patients with moderate AS (aortic valve area >1.0 and <1.5 cm²; and peak aortic jet velocity >2 and <4 m/s, at rest or after dobutamine stress echocardiography) and HFrEF (LVEF <50%). These patients were matched 1:1 for sex, age, estimated glomerular filtration rate, New York Heart Association functional class III to IV, presence of diabetes, LVEF, and body mass index with patients with HFrEF but no AS (i.e., peak aortic jet velocity <2 m/s). The endpoints were all-cause mortality and the composite of death and HF hospitalization.ResultsA total of 262 patients with HFrEF and moderate AS were matched with 262 patients with HFrEF and no AS. Mean follow-up was 2.9 ± 2.2 years. In the moderate AS group, mean aortic valve area was 1.2 ± 0.2 cm², and mean gradient was 14.5 ± 4.7 mm Hg. Moderate AS was associated with an increased risk of mortality (hazard ratio [HR]: 2.98; 95% confidence interval [CI]: 2.08 to 4.31; p < 0.0001) and of the composite of HF hospitalization and mortality (HR: 2.34; 95% CI: 1. 72 to 3.21; p < 0.0001). In the moderate AS group, aortic valve replacement (AVR) performed in 44 patients at a median follow-up time of 10.9 ± 16 months during follow-up was associated with improved survival (HR: 0.59; 95% CI: 0.35 to 0.98; p = 0.04). Notably, surgical AVR was not significantly associated with improved survival (p = 0.92), whereas transcatheter AVR was (HR: 0.43; 95% CI: 0.18 to 1.00; p = 0.05).ConclusionsIn this series of patients with HFrEF, moderate AS was associated with a marked incremental risk of mortality. AVR, and especially transcatheter AVR during follow-up, was associated with improved survival in patients with HFrEF and moderate AS. These findings provide support to the realization of a randomized trial to assess the effect of early transcatheter AVR in patients with HFrEF and moderate AS.     

Avantages et limites des tests sanguins in vitro lymphocytes T/interféron gamma comparativement au test intradermique à la tuberculine pour le diagnostic de tuberculose

The development of in vitro blood tests that measure the delayed hypersensitivity reaction developed after contact with Mycobacterium tuberculosis will change progressively the diagnosis of M. tuberculosis infection. These blood assays (Quantiferon TB Gold^TM, Cellestis, Australia; T-SPOT.TB^TM, Oxford Immunotec, United Kingdom) use specific, complex M. tuberculosis antigens (ESAT-6 and CFP-10), whereas the intradermal Mantoux test is done with tuberculin, a complex mixture of more than 200 antigens. ESAT-6 and CFP-10 are absent from all the BCG vaccine strains used throughout the world. Significant improvement in the specificity with equivalent or increased sensitivity of the in vitro tests compared to the Mantoux test will lead eventually to replacement of the latter.     

Cutaneous trematode <Emphasis Type="Italic">Collyriclum faba</Emphasis> in wild birds in Costa Rica

An adult Collyriclum faba was found in a cutaneous cyst at the base of the lower mandible in a blue-gray tanager (Thraupis episcopus, Thraupidae) examined in the Zona Protectora Las Tablas, Costa Rica on 18 August 2010. A total of 1878 birds belonging to 217 species were examined in the country during 2004, 2009, and 2010. C. faba was found for the first time in blue-gray tanager and for the first time in Costa Rica as well.