Age has historically been used to predict negative post-surgical outcomes. The concept of frailty was introduced to explain the discrepancies that exist between patients’ chronological and ...physiological age. The efficacy of the modified frailty index (mFI) to predict surgical risk is not clear.
We sought to synthesize the current literature to quantify the impact of frailty as a prognostic indicator across all surgical specialties.
Pubmed and Cochrane databases were screened from inception to 1 January 2018.
Studies utilizing the modified Frailty Index (mFI) as a post-operative indicator of any type of surgery. The mFI was selected based on a preliminary search showing it to be the most commonly applied index in surgical cohorts.
Articles were selected via a two-stage process undertaken by two reviewers (AP and DS). Statistical analysis was performed in Revman (Review manager V5.3). The random-effects model was used to calculate the Risk Ratios (RR).
The primary outcomes: post-operative complications, re-admission, re-operation, discharge to a skilled care facility, and mortality.
This meta-analysis of 16 studies randomizes 683,487 patients, 444,885 frail, from gastrointestinal, vascular, orthopedic, urogenital, head and neck, emergency, neurological, oncological, cardiothoracic, as well as general surgery cohorts. Frail patients were more likely to experience complications (RR 1.48, 95%CI 1.35–1.61; p < 0.001), major complications (RR 2.03, 95%CI 1.26–3.29; p = 0.004), and wound complications (RR 1.52, 95%CI 1.47–1.57; p < 0.001). Furthermore, frail patients had higher risk of readmission (RR 1.61, 95%CI 1.44–1.80; p < 0.001) and discharge to skilled care (RR 2.15, 95%CI 1.92–2.40; p < 0.001). Notably, the risk of mortality was 4.19 times more likely in frail patients (95% CI 2.96–5.92; p < 0.001).
and Relevance: This study is the first to synthesize the evidence across multiple surgical specialties and demonstrates that the mFI is an underappreciated prognostic indicator that strongly correlates with the risk of post-surgical morbidity and mortality. This supports that formal incorporation of pre-operative frailty assessment improves surgical decision-making.
•The mFI correlates with higher rates of post-operative complications, readmission, reoperation, and mortality.•Formal incorporation of preoperative frailty assessment using the mFI can improve surgical risk stratification.
Delay in Photoemission Schultze, M; Fiess, M; Karpowicz, N ...
Science (American Association for the Advancement of Science),
06/2010, Letnik:
328, Številka:
5986
Journal Article
Recenzirano
Odprti dostop
Photoemission from atoms is assumed to occur instantly in response to incident radiation and provides the basis for setting the zero of time in clocking atomic-scale electron motion. We used ...attosecond metrology to reveal a delay of Formula: see text attoseconds in the emission of electrons liberated from the 2p orbitals of neon atoms with respect to those released from the 2s orbital by the same 100-electron volt light pulse. Small differences in the timing of photoemission from different quantum states provide a probe for modeling many-electron dynamics. Theoretical models refined with the help of attosecond timing metrology may provide insight into electron correlations and allow the setting of the zero of time in atomic-scale chronoscopy with a precision of a few attoseconds.
The propagation and transport of electrons in crystals is a fundamental process pertaining to the functioning of most electronic devices. Microscopic theories describe this phenomenon as being based ...on the motion of Bloch wave packets. These wave packets are superpositions of individual Bloch states with the group velocity determined by the dispersion of the electronic band structure near the central wavevector in momentum space. This concept has been verified experimentally in artificial superlattices by the observation of Bloch oscillations--periodic oscillations of electrons in real and momentum space. Here we present a direct observation of electron wave packet motion in a real-space and real-time experiment, on length and time scales shorter than the Bloch oscillation amplitude and period. We show that attosecond metrology (1 as = 10(-18) seconds) now enables quantitative insight into weakly disturbed electron wave packet propagation on the atomic length scale without being hampered by scattering effects, which inevitably occur over macroscopic propagation length scales. We use sub-femtosecond (less than 10(-15) seconds) extreme-ultraviolet light pulses to launch photoelectron wave packets inside a tungsten crystal that is covered by magnesium films of varied, well-defined thicknesses of a few ångströms. Probing the moment of arrival of the wave packets at the surface with attosecond precision reveals free-electron-like, ballistic propagation behaviour inside the magnesium adlayer--constituting the semi-classical limit of Bloch wave packet motion. Real-time access to electron transport through atomic layers and interfaces promises unprecedented insight into phenomena that may enable the scaling of electronic and photonic circuits to atomic dimensions. In addition, this experiment allows us to determine the penetration depth of electrical fields at optical frequencies at solid interfaces on the atomic scale.
The opposing actions of myosin light chain kinase and myosin light chain phosphatase (MLCP) determine the level of myosin regulatory light chain (RLC) phosphorylation and thereby determine the ...generation of force in smooth muscle (SM) as well as non‐muscle myosin II regulated cell migration. The MLCP regulatory subunit (MYPT1) is expressed as two isoforms due to alternative splicing of a central exon. Testing the hypothesis that the two MYPT1 splice variants have different functions, we quantify the expression of the MYPT1 exon‐inclusion isoform (MYPT1‐L) to account for 70 – 90% of total MYPT1 protein in vascular and visceral SM. Endogenous MYPT1‐L co‐localized with stress fibers in cultured SMCs, while over‐expressed MYPT1‐S localizes to the lamellipodia of migrating cells. We hypothesize that MYPT1‐S dephosphorylates members of the Ezrin/Radixin/Moesin family of proteins in the lamellipodium, and opposes the actions of Rho Kinase and MLCK in the regulation of membrane protrusions and focal adhesion dynamics during cell migration. Further, we demonstrate translocation of MYPT1 from the cytosol to SMC membranes in rat cerebral vessels upon stimulation with the RhoA‐activating phospholipid sphingosine‐1‐phosphate, and suggest that the translocation results in increased RLC20 phosphorylation, in part due to its absence from the actin‐myosin contractile apparatus, and by phospho‐inhibition of MYPT1. In summary, we propose that the spatial distributions of MYPT1 isoforms are indicative of specialized roles for controlling Ser/Thr phosphorylation of focal adhesions and cytoskeletal proteins.
Supported by NIH POI HL48807
The aims of this study were to develop a method for deriving purified populations of contractile smooth muscle cells (SMCs) from embryonic stem cells (ESCs) and to characterize their function. ...Transgenic ESC lines were generated that stably expressed a puromycin-resistance gene under the control of either a smooth muscle alpha-actin (SMalphaAlpha) or smooth muscle-myosin heavy chain (SM-MHC) promoter. Negative selection, either overnight or for 3 days, was then used to purify SMCs from embryoid bodies. Purified SMCs expressed multiple SMC markers by immunofluorescence, immunoblotting, quantitative reverse transcription-polymerase chain reaction, and flow cytometry and were designated APSCs (SMalphaAlpha-puromycin-selected cells) or MPSCs (SM-MHC-puromycin-selected cells), respectively. Both SMC lines displayed agonist-induced Ca(2+) transients, expressed functional Ca(2+) channels, and generated contractile force when aggregated within collagen gels and stimulated with vasoactive agonists, such as endothelin-1, or in response to depolarization with KCl. Importantly, subcutaneous injection of APSCs or MPSCs subjected to 18 hours of puromycin selection led to the formation of teratomas, presumably due to residual contamination by pluripotent stem cells. In contrast, APSCs or MPSCs subjected to prolonged puromycin selection for 3 days did not form teratomas in vivo. These studies describe for the first time a method for generating relatively pure populations of SMCs from ESCs which display appropriate excitation and contractile responses to vasoactive agonists. However, studies also indicate the potential for teratoma development in ESC-derived cell lines, even after prolonged differentiation, highlighting the critical requirement for efficient methods of separating differentiated cells from residual pluripotent precursors in future studies that use ESC derivatives, whether SMC or other cell types, in tissue engineering applications.
The most accurate method of clinical MR spectroscopy (MRS) interpretation remains an open question. We sought to construct a logistic regression (LR) pattern recognition model for the discrimination ...of neoplastic from nonneoplastic brain lesions with MR imaging-guided single-voxel proton MRS data. We compared the LR sensitivity, specificity, and receiver operator characteristic (ROC) curve area (Az) with the sensitivity and specificity of blinded and unblinded qualitative MRS interpretations and a choline (Cho)/N-acetylaspartate (NAA) amplitude ratio criterion.
Consecutive patients with suspected brain neoplasms or recurrent neoplasia referred for MRS were enrolled once final diagnoses were established by histopathologic examination or serial neurologic examinations, laboratory data, and imaging studies. Control spectra from healthy adult volunteers were included. An LR model was constructed with 10 input variables, including seven metabolite resonance amplitudes, unsuppressed brain water content, water line width, and the final diagnosis (neoplasm versus nonneoplasm). The LR model output was the probability of tumor, for which a cutoff value was chosen to obtain comparable sensitivity and specificity. The LR sensitivity and specificity were compared with those of qualitative blinded interpretations from two readers (designated A and B), qualitative unblinded interpretations (in aggregate) from a group of five staff neuroradiologists and a spectroscopist, and a quantitative Cho/NAA amplitude ratio > 1 threshold for tumor. Sensitivities and specificities for each method were compared with McNemar's chi square analysis for binary tests and matched data with a significance level of 5%. ROC analyses were performed where possible, and Az values were compared with Metz's method (CORROC2) with a 5% significance level.
Of the 99 cases enrolled, 86 had neoplasms and 13 had nonneoplastic diagnoses. The discrimination of neoplastic from control spectra was trivial with the LR, reflecting high homogeneity among the control spectra. An LR cutoff probability for tumor of 0.8 yielded a specificity of 87%, a comparable sensitivity of 85%, and an area under the ROC curve of 0.96. Sensitivities, specificities, and ROC areas (where available) for the other methods were, on average, 82%, 74%, and 0.82, respectively, for readers A and B, 89% (sensitivity) and 92% (specificity) for the group of unblinded readers, and 79% (sensitivity), 77% (specificity), and 0.84 (Az) for the Cho/NAA > 1 criterion. McNemar's analysis yielded significant differences in sensitivity (n approximately 86 neoplasms) between the LR and reader A, and between the LR and the Cho/NAA > 1 criterion. The differences in specificity between the LR and all other methods were not significant (n approximately 13 nonneoplasms). Metz's analysis revealed a significant difference in Az between the LR and the Cho/NAA ratio criterion.
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