Cancer causes considerable suffering and 80% of advanced cancer patients experience moderate to severe pain. Surgical tumor excision remains a cornerstone of primary cancer treatment, but is also ...recognized as one of the greatest risk factors for metastatic spread. The perioperative period, characterized by the surgical stress response, pharmacologic-induced angiogenesis, and immunomodulation results in a physiologic environment that supports tumor spread and distant reimplantation.In the perioperative period, anesthesiologists may have a brief and uniquewindow of opportunity to modulate the unwanted consequences of the stressresponse on the immune system and minimize residual disease. This reviewdiscusses the current research on analgesic therapies and their impact ondisease progression, followed by an evidence-based evaluation of perioperativepain interventions and medications.
Adverse cardiovascular events are a leading cause of perioperative morbidity and mortality. The definitions of perioperative cardiovascular adverse events are heterogeneous. As part of the ...international Standardized Endpoints in Perioperative Medicine initiative, this study aimed to find consensus amongst clinical trialists on a set of standardised and valid cardiovascular outcomes for use in future perioperative clinical trials.
We identified currently used perioperative cardiovascular outcomes by a systematic review of the anaesthesia and perioperative medicine literature (PubMed/Ovid, Embase, and Cochrane Library). We performed a three-stage Delphi consensus-gaining process that involved 55 clinician researchers worldwide. Cardiovascular outcomes were first shortlisted and the most suitable definitions determined. These cardiovascular outcomes were then assessed for validity, reliability, feasibility, and clarity.
We identified 18 cardiovascular outcomes. Participation in the three Delphi rounds was 100% (n=19), 71% (n=55), and 89% (n=17), respectively. A final list of nine cardiovascular outcomes was elicited from the consensus: myocardial infarction, myocardial injury, cardiovascular death, non-fatal cardiac arrest, coronary revascularisation, major adverse cardiac events, pulmonary embolism, deep vein thrombosis, and atrial fibrillation. These nine cardiovascular outcomes were rated by the majority of experts as valid, reliable, feasible, and clearly defined.
These nine consensus cardiovascular outcomes can be confidently used as endpoints in clinical trials designed to evaluate perioperative interventions with the goal of improving perioperative outcomes.
Perioperative infection and sepsis are of fundamental concern to perioperative clinicians. However, standardised endpoints are either poorly defined or not routinely implemented. The Standardised ...Endpoints in Perioperative Medicine (StEP) initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials.
We undertook a systematic review to identify measures of infection and sepsis used in the perioperative literature. A multi-round Delphi consensus process that included more than 60 clinician researchers was then used to refine a recommended list of outcome measures.
A literature search yielded 1857 titles of which 255 met inclusion criteria for endpoint extraction. A long list of endpoints, with definitions and timescales, was generated and those potentially relevant to infection and sepsis circulated to the theme subgroup and then the wider StEP-COMPAC working group, undergoing a three-stage Delphi process. The response rates for Delphi rounds 1, 3, and 3 were 89% (n=8), 67% (n=62), and 80% (n=8), respectively. A set of 13 endpoints including fever, surgical site, and organ-specific infections as defined by the US Centres for Disease Control and Sepsis-3 are proposed for future use.
We defined a consensus list of standardised endpoints related to infection and sepsis for perioperative trials using an established and rigorous approach. Each endpoint was evaluated with respect to validity, reliability, feasibility, and patient centredness. One or more of these should be considered for inclusion in future perioperative clinical trials assessing infection, sepsis, or both, thereby permitting synthesis and comparison of future results.
Mortality, morbidity, and organ failure are important and common serious harms after surgery. However, there are many candidate measures to describe these outcome domains. Definitions of these ...measures are highly variable, and validity is often unclear. As part of the International Standardised Endpoints in Perioperative Medicine (StEP) initiative, this study aimed to derive a set of standardised and valid measures of mortality, morbidity, and organ failure for use in perioperative clinical trials.
Three domains of endpoints (mortality, morbidity, and organ failure) were explored through systematic literature review and a three-stage Delphi consensus process using methods consistently applied across the StEP initiative. Reliability, feasibility, and patient-centredness were assessed in round 3 of the consensus process.
A high level of consensus was achieved for two mortality time points, 30-day and 1-yr mortality, and these two measures are recommended. No organ failure endpoints achieved threshold criteria for consensus recommendation. The Clavien–Dindo classification of complications achieved threshold criteria for consensus in round 2 of the Delphi process but did not achieve the threshold criteria in round 3 where it scored equivalently to the Post Operative Morbidity Survey. Clavien–Dindo therefore received conditional endorsement as the most widely used measure. No composite measures of organ failure achieved an acceptable level of consensus.
Both 30-day and 1-yr mortality measures are recommended. No measure is recommended for organ failure. One measure (Clavien–Dindo) is conditionally endorsed for postoperative morbidity, but our findings suggest that no single endpoint offers a reliable and valid measure to describe perioperative morbidity that is not dependent on the quality of deli-vered care. Further refinement of current measures, or development of novel measures, of postoperative morbidity might improve consensus in this area.
Human reaction to cold stress and hypothermia involves shivering. Another form of overt shaking, postoperative shivering, has been attributed as a thermoregulatory response to postoperative ...hypothermia. Analysis of the normal human shivering pattern showed a synchronized, slow amplitude modulation (six to eight cycles/min) over all muscles sampled. In addition, there was a frequency of 8 to 10 Hz associated with each low-frequency amplitude modulation. EMG signals from postoperative patients revealed none of the major patterns seen in thermal-induced shivering. Cold-induced vasodilation also was studied and found to occur simultaneously in all cold-stressed fingers regardless of size or innervation. Thermal shivering and cold-induced vasodilation are considered to be manifestations of central neural oscillators.
The ability to capture radioactive iodine species is crucial for nuclear accident preparedness and nuclear waste treatment; however, it remains a challenge. Here we report a new readily obtainable ...nitrogen-rich nonporous cage (
) based on bipyridine building blocks that supports iodine capture. This cage is able to capture not only volatile iodine in vapor form but also iodine dissolved in various organic solvents or aqueous media with an iodine uptake capacity of up to 3.23 g g
. The iodine within the cage (
) can be released quickly upon immersing the bound solid form in DMF, allowing for control over acylation reactions. The cage solids reported here could be reused several times without substantial loss in their iodine capture performance. The effectiveness of the present system is ascribed to its ability to support strong iodine-bipyridine nitrogen lone pair interactions.
The use of molecular crystalline materials for the separation and purification of chemical raw materials, particularly polar compounds with similar physical and chemical properties, represents an ...ongoing challenge. This is particularly true for volatile feedstocks that form binary azeotropes. Here we report a new cavity-extended version of calix4pyrrole (C4P) that readily forms nonporous adaptive crystals (NACs). These C4P-based NACs allow pyridine to be separated from toluene/pyridine mixtures with nearly 100% purity, as well as the removal of 1,4-dioxane from 1,4-dioxane/water mixtures with high adsorption capacity. Removal of the polar guest (pyridine or 1,4-dioxane) from the guest-loaded NACs by heating under vacuum produces the guest-free crystalline form. In the case of both guests, the C4P material could be reused as demonstrated through 10 uptake and release cycles without apparent performance loss.
The toxicity, corrosiveness, and volatility of elemental bromine presents challenges for its safe storage and transportation. Purification from other halogens is also difficult. Here, we report an ...easy-to-prepare calix4pyrrole-based azo-bridged porous organic polymer (C4P-POP) that supports efficient bromine capture. C4P-POP was found to capture bromine as a vapor and from a cyclohexane source phase with maximum uptake capacities of 3.6 and 3.4 g·g–1, respectively. Flow-through adsorption experiments revealed that C4P-POP removes 80% of the bromine from a 4.0 mM cyclohexane solution at a flow rate of 45 mL·h–1. C4P-POP also allowed the selective capture of bromine from a 1:1 mixture of bromine and iodine in cyclohexane.
The design and synthesis of novel macrocyclic host molecules continues to attract attention because such species play important roles in supramolecular chemistry. However, the discovery of new ...classes of macrocycles presents a considerable challenge due to the need to embody by design effective molecular recognition features, as well as ideally the development of synthetic routes that permit further functionalization. In 2010, we reported a new class of macrocyclic hosts: a set of tetracationic imidazolium macrocycles, which we termed "Texas-sized" molecular boxes (TxSBs) in homage to Stoddart's classic "blue box" (CBPQT
). Compared with the rigid blue box, the first generation TxSB displayed considerably greater conformational flexibility and a relatively large central cavity, making it a good host for a variety of electron-rich guests. In this review, we provide a comprehensive summary of TxSB chemistry, detailing our recent progress in the area of anion-responsive supramolecular self-assembly and applications of the underlying chemistry to water purification, information storage, and controlled drug release. Our objective is to provide not only a review of the fundamental findings, but also to outline future research directions where TxSBs and their constructs may have a role to play.
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