Acute ischemic heart disease and interventional cardiology: a time for pause

BACKGROUND: A major change has occurred in the last few years in the therapeutic approach to patients presenting with all forms of acute coronary syndromes. Whether or not these patients present initially to tertiary cardiac care centers, they are now routinely referred for early coronary angiography and increasingly undergo percutaneous revascularization. This practice is driven primarily by the angiographic image and technical feasibility. Concomitantly, there has been a decline in expectant or ischemia-guided medical management based on specific clinical presentation, response to initial treatment, and results of noninvasive stratification. This 'tertiarization' of acute coronary care has been fuelled by the increasing sophistication of the cardiac armamentarium, the peer-reviewed publication of clinical studies purporting to show the superiority of invasive cardiac interventions, and predominantly supporting (non-peer-reviewed) editorials, newsletters, and opinion pieces. DISCUSSION: This review presents another perspective, based on a critical reexamination of the evidence. The topics addressed are: reperfusion treatment of ST-elevation myocardial infarction; the indications for invasive intervention following thrombolysis; the role of invasive management in non-ST-elevation myocardial infarction and unstable angina; and cost-effectiveness and real world considerations. A few cases encountered in recent practice in community and tertiary hospitals are presented for illustrative purposes The numerous and far-reaching scientific, economic, and philosophical implications that are a consequence of this marked change in clinical practice as well as healthcare, decisional and conflict of interest issues are explored. SUMMARY: The weight of evidence does not support the contemporary unfocused broad use of invasive interventional procedures across the spectrum of acute coronary clinical presentations. Excessive and unselective recourse to these procedures has deleterious implications for the organization of cardiac health care and undesirable economic, scientific and intellectual consequences. It is suggested that there is need for a new equilibrium based on more refined clinical risk stratification in the treatment of patients who present with acute coronary syndromes

Saethre-Chotzen syndrome : cranofacial anomalies caused by genetic changes in the TWIST gene

In this thesis, one of the most frequently occurring and most variable craniosynostosis syndromes was investigated; Saethre-Chotzen syndrome. Craniosynostosis is the premature obliteration of cranial sutures in the developing embryo. It can also occur in the first few months of life. Saethre-Chotzen syndrome is, besides craniosynostosis, characterized by specific facial and limb abnormalities, of which the most frequently reported are ptosis, prominent crus helicis, cutaneous syndactyly of digit 2 and 3 on both hands and feet, and broad halluces. Saethre-Chotzen syndrome has been linked to the TWIST gene on chromosome 7p21.1. Mutations in and variably sized deletions of this gene can be found in patients with clinical features of Saethre-Chotzen syndrome. The latter, TWIST deletions, often also include part of the surrounding chromosome 7p and are reported to be associated with mental retardation. In Saethre-Chotzen patients, in whom neither a mutation nor a deletion of TWIST had been found, the FGFR3 P250R mutation was in some cases detected. This mutation has specifically been linked to Muenke syndrome that is characterized by unior bicoronal synostosis and slight facial dysmorphology. However, a Saethre-Chotzen like phenotype can also result from this mutation. Because of the possible overlap of Saethre-Chotzen with Muenke syndrome, these syndromes were studied in order to provide clinical criteria that discriminate between the two (chapter 4). Many phenotypic features occur in both syndromes. In addition, although unicoronal synostosis occurs slightly more frequently in Muenke syndrome, unicoronal and bicoronal synostosis are seen in both syndromes. The discrimination between Saethre-Chotzen and Muenke is often not made easily and the associated genes, TWIST and FGFR3, respectively, are simultaneously tested for pathogenic m

Molecular dynamics simulation of aqueous solutions of 26-unit segments of p(NIPAAm) and of p(NIPAAm) "doped" with amino acid based comonomers

We have performed 75-ns molecular dynamics (MD) simulations of aqueous solutions of a 26-unit NIPAAm oligomer at two temperatures, 302 and 315 K, below and above the experimentally determined lower critical solution temperature (LCST) of p(NIPAAm). We have been able to show that at 315 K the oligomer assumes a compact form, while it keeps a more extended form at 302 K. A similar behavior has been demonstrated for a similar NIPAAm oligomer, where two units had been substituted by methacryloyl-l-valine (MAVA) comonomers, one of them being charged and one neutral. For another analogous oligomer, where the same units had been substituted by methacryloyl-l-leucine (MALEU) comonomers, no transition from the extended to the more compact conformation has been found within the same simulation time. Statistical analysis of the trajectories indicates that this transition is related to the dynamics of the oligomer backbone, and to the formation of intramolecular hydrogen bonds and water-bridges between distant units of the solute. In the MAVA case, we have also evidenced an important role of the neutral MAVA comonomer in stabilizing the compact coiled structure. In the MALEU case, the corresponding comonomer is not equally efficacious and, possibly, is even hindering the readjustment of the oligomer backbone. Finally the self-diffusion coefficient of water molecules surrounding the oligomers at the two temperatures for selected relevant times is observed to characteristically depend on the distance from the solute molecules

Nonlinear beam self-cleaning in a coupled cavity composite laser based on multimode fiber

We study a coupled cavity laser configuration where a passively Q-switched Nd:YAG microchip laser is combined with an extended cavity, including a doped multimode fiber. For appropriate coupling levels with the extended cavity, we observed that beam selfcleaning was induced in the multimode fiber thanks to nonlinear modal coupling, leading to a quasi-single mode laser output. In the regime of beam self-cleaning, laser pulse duration was reduced from 525 to 225 ps. We also observed a Q-switched mode-locked operation, where spatial self-cleaning was accompanied by far-detuned nonlinear frequency conversion in the active multimode fiber

Constraints on models of the Higgs boson with exotic spin and parity using decays to bottom-antibottom quarks in the full CDF data set

A search for particles with the same mass and couplings as those of the standard model Higgs boson but different spin and parity quantum numbers is presented. We test two specific alternative Higgs boson hypotheses: a pseudoscalar Higgs boson with spin-parity JP=0- and a gravitonlike Higgs boson with JP=2+, assuming for both a mass of 125GeV/c2. We search for these exotic states produced in association with a vector boson and decaying into a bottom-antibottom quark pair. The vector boson is reconstructed through its decay into an electron or muon pair, or an electron or muon and a neutrino, or it is inferred from an imbalance in total transverse momentum. We use expected kinematic differences between events containing exotic Higgs bosons and those containing standard model Higgs bosons. The data were collected by the CDF experiment at the Tevatron proton-antiproton collider, operating at a center-of-mass energy of s=1.96TeV, and correspond to an integrated luminosity of 9.45fb-1. We exclude deviations from the predictions of the standard model with a Higgs boson of mass 125GeV/c2 at the level of 5 standard deviations, assuming signal strengths for exotic boson production equal to the prediction for the standard model Higgs boson, and set upper limits of approximately 30% relative to the standard model rate on the possible rate of production of each exotic state

Search for Higgs-like particles produced in association with bottom quarks in proton-antiproton collisions

We report on a search for a spin-zero non-standard model particle in proton-antiproton collisions collected by the Collider Detector at Fermilab at a center-of-mass-energy of 1.96 TeV. This particle, the phi boson, is expected to decay into a bottom-antibottom quark pair and to be produced in association with at least one bottom quark. The data sample consists of events with three jets identified as initiated by bottom quarks and corresponds to 5.4 fb(-1) of integrated luminosity. In each event, the invariant mass of the two most energetic jets is studied by looking for deviations from the multijet background, which is modeled using data. No evidence is found for such a particle. Exclusion upper limits ranging from 20 to 2 pb are set for the product of production cross sections times branching fraction for the hypothetical phi boson with mass between 100 and 300 GeV/c(2). These are the most stringent constraints to date.Peer reviewe

Tevatron Combination of Single-Top-Quark Cross Sections and Determination of the Magnitude of the Cabibbo-Kobayashi-Maskawa Matrix Element Vtb

We present the final combination of CDF and D0 measurements of cross sections for single-top-quark production in proton-antiproton collisions at a center-of-mass energy of 1.96 TeV. The data correspond to total integrated luminosities of up to 9.7??fb-1 per experiment. The t-channel cross section is measured to be st=2.25+0.29-0.31??pb. We also present the combinations of the two-dimensional measurements of the s- vs t-channel cross section. In addition, we give the combination of the s+t channel cross section measurement resulting in ss+t=3.30+0.52-0.40??pb, without assuming the standard model value for the ratio ss/st. The resulting value of the magnitude of the top-to-bottom quark coupling is |Vtb|=1.02+0.06-0.05, corresponding to |Vtb|>0.92 at the 95% C.L

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially