The intracellular environment is partitioned into functionally distinct compartments containing specific sets of molecules and reactions. Biomolecular condensates, also referred to as membrane-less organelles, are diverse and abundant cellular compartments that lack membranous enclosures. Molecules assemble into condensates by phase separation; multivalent weak interactions drive molecules to separate from their surroundings and concentrate in discrete locations. Biomolecular condensates exist in all eukaryotes and in some prokaryotes, and participate in various essential house-keeping, stress-response and cell type-specific processes. An increasing number of recent studies link abnormal condensate formation, composition and material properties to a number of disease states. In this review, we discuss current knowledge and models describing the regulation of condensates and how they become dysregulated in neurodegeneration and cancer. Further research on the regulation of biomolecular phase separation will help us to better understand their role in cell physiology and disease.

Biomolecular condensates in neurodegeneration and cancer.

Editor’s PerspectiveWhat We Already Know about This TopicRecommendations for anesthetic care are often difficult to implement in the intraoperative setting because of the requirement for continuous attentionWhat This Article Tells Us That Is NewClosed-loop, automated management of anesthetic, analge

Anesthetic Management Using Multiple Closed-loop Systems and Delayed Neurocognitive Recovery: A Randomized Controlled Trial.

The number of elderly patients who frequently access health care services is increasing worldwide. While anesthesiologists are developing the expertise to care for these elderly patients, areas of concern remain. We conducted a comprehensive search of major international databases (PubMed, Embase, and Cochrane) and a Korean database (KoreaMed) to review preoperative considerations, intraoperative management, and postoperative problems when anesthetizing elderly patients. Preoperative preparation of elderly patients included functional assessment to identify preexisting cognitive impairment or cardiopulmonary reserve, depression, frailty, nutrition, polypharmacy, and anticoagulation issues. Intraoperative management included anesthetic mode and pharmacology, monitoring, intravenous fluid or transfusion management, lung-protective ventilation, and prevention of hypothermia. Postoperative checklists included perioperative analgesia, postoperative delirium and cognitive dysfunction, and other complications. A higher level of perioperative care was required for older surgical patients, as multiple chronic diseases often makes them prone to developing postoperative complications, including functional decline and loss of independence. Although the guiding evidence remains poor so far, elderly patients have to be provided optimal perioperative care through close interdisciplinary, interprofessional, and cross-sectional collaboration to minimize unwanted postoperative outcomes. Furthermore, along with adequate anesthetic care, well-planned postoperative care should begin immediately after surgery and extend until discharge.

/pdf/anesthetic-management-of-geriatric-patients-1aroysa3ep.pdf

Anesthetic management of geriatric patients.

Elective surgical pathways offer a particular opportunity to plan radical change in the way care is delivered, based on patient need rather than provider convenience. Peri-operative pathway redesign enables improved patient experience of care (including quality and satisfaction), population/public health, and healthcare value (outcome per unit of currency). Among physicians with the skills to work within peri-operative medicine, anaesthetists are well positioned to lead the re-engineering of such pathways. Re-engineered pre-operative pathways open up opportunities for intervention before surgery including shared decision-making, comorbidity management and collaborative behavioural change. Individualised, risk-adapted, intra-operative interventions will drive more reliable and consistent care. Risk-adapted postoperative care, particularly around transitions of care, has a significant role in improving value through peri-operative medicine. Improved integration with primary care providers offers the potential for minimising errors around transitions of care before and after surgery, as well as maximising opportunities for population health interventions, including lifestyle modification (e.g. activity/exercise, smoking and/or alcohol cessation), pain management and sleep medicine. Systematic data collection focused on quality improvement is essential to drive continuous clinical improvement and will be enabled by technological development in predictive analytics, systems modelling and artificial intelligence.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/anae.14513

Peri-operative care pathways: re-engineering care to achieve the 'triple aim'.

Background The present study aimed at evaluating the effect of a haemodynamic algorithm using SV maximisation by non-invasive photoplethysmography (interventional group) on the incidence of postoperative complications compared with a control group using intermittent mean arterial pressure. Methods The non-blinded parallel-group trial randomised low-risk patients undergoing colorectal surgery into either interventional group or control group. The primary outcome was the incidence of patients with at least one complication during the 30 days following surgery. The secondary outcomes were the total number of complications, the length of hospital stay and postoperative mortality. A meta-analysis of randomised trials comparing perioperative haemodynamic optimisation (interventional group) using photoplethysmography with control group was performed to assess the external validity. Results Among 160 randomised patients, 159 were analysed (80 and 79 in interventional and control groups, respectively). Demographic characteristics were similar in both groups. Postoperative complications occurred in 40 (50%) and 34 (43%) patients in the interventional and control groups, respectively (P = 0.471). There were no significant differences between the two groups regarding the total number of complications (P = 0.078), the hospital length of stay (P = 0.960), or postoperative mortality (P = 1.000). In the meta-analysis including 1089 patients in 7 randomised controlled studies, 203 (38%) and 221 (40%) patients suffered from at least one complication following surgery [risk ratio 0.89 (95% CI 0.68–1.17), P = 0.407] in interventional and control groups, respectively. Conclusions Based on the findings of the present study and meta-analysis, a haemodynamic perioperative algorithm using SV maximisation by non-invasive photoplethysmography cannot reduce postoperative morbidity.

Perioperative non-invasive haemodynamic optimisation using photoplethysmography: a randomised controlled trial and meta-analysis

Introduction In elderly patients, goal-directed haemodynamic therapy (GDHT), depth of anaesthesia monitoring and lung-protective ventilation have been shown to improve postoperative outcomes The aim of this study was to evaluate current practices concerning strategies of anaesthesia optimisation in patients aged ≥ 75 years Patients and methods A multicentre observational study was performed from February to May 2015 in 23 French academic centres On 30 consecutive days in each centre, patients ≥ 75 years with at least one major comorbidity undergoing elective or emergency procedures (femoral-neck fractures surgery, intraperitoneal abdominal surgery or vascular surgery) were included Patient characteristics and data related to GHDT, management of hypotension, monitoring of temperature and depth of anaesthesia, lung ventilation, point of care haemoglobin testing were collected Results In total, 807 patients were included Only 2% of patients [95% CI: 1–3] received GHDT in full accordance with guidelines Depth of anaesthesia monitoring was largely performed (53% [95% CI: 50–56]) The multifaceted strategy of lung-protective ventilation combining low tidal volumes (6–8 mL/kg), PEEP of 5–8 cm cmH2O, and repeated recruitment manoeuvres, was performed in only 4% [95% CI: 3–5] of patients A centre effect was a major determinant of variation concerning implementation of these strategies Discussion In patients’ ≥ 75 years, strategies of anaesthesia optimisation are not in accordance with eligible guidelines Implementation of these techniques varies independently of factors related to the patient or the type of surgery and may be dependent on the generated constraints

A multicentre observational study on management of general anaesthesia in elderly patients at high-risk of postoperative adverse outcomes.

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A multicentre observational study on management of general anaesthesia in elderly patients at high-risk of postoperative adverse outcomes.