Commercial brain function monitors for depth of anesthesia have been available for more than 2 decades; there are currently more than 10 devices on the market. Advances in this field are evidenced by ...updated versions of existing monitors, development of new monitors, and increasing research unveiling the mechanisms of anesthesia on the brain. Electroencephalography signal processing forms an integral part of the technology supporting the brain function monitors for derivation of a depth-of-anesthesia index. This article aims to provide a better understanding of the technology and functionality behind these monitors. This review will highlight the general design principles of these devices and the crucial stages in electroencephalography signal processing and classification, with a focus on the key mathematical techniques used in algorithm development for final derivation of the index representing anesthetic state. We will briefly discuss the advantages and limitations of this technology in the clinical setting as a tool in our repertoire used for optimizing individualized patient care. Also included is a table describing 10 available commercial depth-of-anesthesia monitors.
A recent publication reported that at three hospitals within one academic health system, female surgeons received less surgical block time than male surgeons, suggesting potential gender-based bias ...in operating room scheduling. We examined this observation's generalizability.
Our cross-sectional retrospective cohort study of State of Florida administrative data included all 4,176,551 ambulatory procedural encounters and inpatient elective surgical cases performed January 2017 through December 2019 by 8875 surgeons (1830 female) at all 609 non-federal hospitals and ambulatory surgery centers. There were 1,509,190 lists of cases (i.e., combinations of the same surgeon, facility, and date). Logistic regression adjusted for covariables of decile of surgeon's quarterly cases, surgeon's specialty, quarter, and facility.
Selecting randomly a male and a female surgeons' quarter, for 66% of selections, the male surgeon performed more cases (P < .0001). Without adjustment for quarterly caseloads, lists comprised one case for 44.2% of male and 54.6% of female surgeons (difference 10.4%, P < .0001). A similar result held for lists with one or two cases (difference 9.1%, P < .0001). However, incorporating quarterly operative caseloads, the direction of the observed difference between male and female surgeons was reversed both for case lists with one (-2.1%, P = .03) or one or two cases (-1.8%, P = .05).
Our results confirm the aforementioned single university health system results but show that the differences between male and female surgeons in their lists were not due to systematic bias in operating room scheduling (e.g., completing three brief elective cases in a week on three different workdays) but in their total case numbers. The finding that surgeons performing lists comprising a single case were more often female than male provides a previously unrecognized reason why operating room managers should help facilitate the workload of surgeons performing only one case on operative (anesthesia) workdays.
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There is controversy about how to manage requests by patients or surrogates for treatments that clinicians believe should not be administered.
This multisociety statement provides recommendations to ...prevent and manage intractable disagreements about the use of such treatments in intensive care units.
The recommendations were developed using an iterative consensus process, including expert committee development and peer review by designated committees of each of the participating professional societies (American Thoracic Society, American Association for Critical Care Nurses, American College of Chest Physicians, European Society for Intensive Care Medicine, and Society of Critical Care).
The committee recommends: (1) Institutions should implement strategies to prevent intractable treatment conflicts, including proactive communication and early involvement of expert consultants. (2) The term "potentially inappropriate" should be used, rather than futile, to describe treatments that have at least some chance of accomplishing the effect sought by the patient, but clinicians believe that competing ethical considerations justify not providing them. Clinicians should explain and advocate for the treatment plan they believe is appropriate. Conflicts regarding potentially inappropriate treatments that remain intractable despite intensive communication and negotiation should be managed by a fair process of conflict resolution; this process should include hospital review, attempts to find a willing provider at another institution, and opportunity for external review of decisions. When time pressures make it infeasible to complete all steps of the conflict-resolution process and clinicians have a high degree of certainty that the requested treatment is outside accepted practice, they should seek procedural oversight to the extent allowed by the clinical situation and need not provide the requested treatment. (3) Use of the term "futile" should be restricted to the rare situations in which surrogates request interventions that simply cannot accomplish their intended physiologic goal. Clinicians should not provide futile interventions. (4) The medical profession should lead public engagement efforts and advocate for policies and legislation about when life-prolonging technologies should not be used.
The multisociety statement on responding to requests for potentially inappropriate treatments in intensive care units provides guidance for clinicians to prevent and manage disputes in patients with advanced critical illness.
Cryopreservation of thin tissues such as small animal ovaries, organ slices, skin, and blood vessels has been studied for many years. As long ago as 1980, three dozen organized tissues could be ...listed that had been successfully cryopreserved by freezing, including partial successes with some organs. But the cryopreservation of vascularized tissues adds another level of complexity to tissue preservation, and requires consideration of vascular dynamic issues that must be added to other common factors in tissue cryopreservation. Most early studies illustrate well the pitfalls of delivering and removing cryoprotectants by perfusion, but fortunately, much has been learned since then, and it now appears that the preservation of even whole organs will be possible by vitrification in the foreseeable future. Extension of current work on kidneys to hearts and other organs and limbs could become and remain a new frontier for decades to come. In the meantime, there are at least four lessons learned that may be of assistance for the preservation of non-vascularized tissues as well. First, models of optimized tissue treatment with cryoprotectants developed for organs may be more applicable to non-vascularized tissues than to organs. Second, whole organ research has highlighted the importance of, and possible remedies for, chilling injury which is a factor that is rarely considered in conventional tissue freezing or vitirfication protocols. Chilling injury may depend on cell volume and hence on levels of and gradients in tissue CPA concentration. Third, conventional tissue freezing usually ignores the possibility of cryoprotectant toxicity in the frozen state, a problem that may be reduced by using low-toxicity cryoprotectant mixtures of the kind necessary for vitrifying kidneys. Recent studies indicate that even polymeric agents appear to permeate well enough into unperfused tissues to be beneficial. Finally, use of synthetic ice blockers also appears applicable to non-perfused tissues, and may have benefits even during freezing for the prevention of damaging recrystallization.
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The nature of cryoprotectant toxicity has received little attention. Literature studies are mostly confined to in vivo toxicity data that have little to no relevance to events at low temperatures. ...Cryoprotectant toxicity in the frozen state suggests a rapid mechanism for toxicity that overwhelms the generally protective effects of lower temperatures. Previous evidence argued against generalized protein denaturation as a mechanism of toxicity because (a) toxicity is observed at lower concentrations than those needed to denature proteins, (b) protein destabilization tendency was associated with less toxicity, not more, and (c) preferential exclusion of cryoprotectants from the protein surface implied protein stabilization at lower temperatures. Newer data, however, have reopened the possibility that toxicity may be related to the denaturation of specific proteins. A microarray study showed that vitrification solution exposure increased heat shock protein gene expression, increased transcription of genes in the ERK and JNK pathways, and induced 8 genes associated with ribosome biogenesis, all suggesting a reaction to protein denaturation. The correlation between toxicity in organized tissue and qv∗ is also compatible with protein denaturation as the primary mechanism of “non-specific” toxicity. Although individual cryoprotectants may be used at sub-denaturing concentrations in vitrification solutions, their cumulative effect could become denaturing, especially if cryoprotectant-mediated destabilization summates with cold destabilization. Pertinent to this possibility, an additional microarray study suggests that chilling injury may be largely related to protein denaturation as well, which raises the question as to whether chilling injury in systems prepared for vitrification may in large part be induced by the presence of the vitrification solution. If so, chilling injury may be considered a toxic effect of cryoprotectants at deep subzero temperatures, consistent with the manifestation of such toxic effects in frozen-thawed systems.
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STUDY QUESTION
What are the appropriate conditions to vitrify the macaque ovarian cortex in a large-volume, closed system that will preserve functional pre-antral follicles?
SUMMARY ANSWER
The ...combination of glycerol, ethylene glycol (EG) and polymers with cooling in liquid nitrogen (LN2) vapor and a two-step warming procedure was able to preserve tissue and follicle morphology as well as function of a small population of secondary follicles in the macaque ovarian cortex following vitrification in a closed system.
WHAT IS KNOWN ALREADY
For prepubertal cancer patients or those who require immediate cancer therapy, ovarian tissue cryopreservation offers the only hope for future fertility. However, the efficacy of live birth from the transplantation of cryopreserved ovarian tissue is still unclear. In addition, live birth from cryopreserved ovarian tissue has only been demonstrated after tissue autotransplantation, which poses the risk of transmitting metastatic cancer cells back to the cancer survivor in certain cancers.
STUDY DESIGN, SIZE, DURATION
Non-human primate model, n = 4, randomized, control versus treatment. End-points were collected from tissue histology, tissue culture (48 h) and isolated secondary follicle culture (6 weeks).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Two vitrification solutions (VSs) containing EG + glycerol (VEG) and EG + dimethylsulfoxide (VED) were examined for vitrification, devitrification and thermodynamic properties. Once the optimal VS was determined, macaque ovarian cortical pieces (3 × 3 × 0.5 mm3) were divided into fresh and two vitrified groups (VEG and VED). For the vitrification groups, tissues were exposed to 1/4, 1/2 and 1× VS for 5 min/step as well as 1× VS + polymers for 1 min at 37°C, loaded into high-security straws with 1 ml of VS + polymers, heat sealed and cooled in LN2 vapor. Samples were warmed in a 40°C water bath and cryoprotective agents were diluted with 1, 0.5, 0.25 and 0 M sucrose. Tissues were fixed for histological analysis and cultured with bromodeoxyuridine (BrdU). Secondary follicles from VEG tissues were encapsulated and cultured (n = 24/treatment/animal). Follicle health, diameter and steroid progesterone, androstenedione (A4), estradiol (E2) production were analyzed weekly.
MAIN RESULTS AND THE ROLE OF CHANCE
Dense stroma and intact pre-antral follicles were observed using VS containing 27% glycerol, 27% EG and 0.8% polymers with cooling in LN2 vapor and a two-step warming. Higher cooling and warming rates led to fracturing. BrdU uptake was evident in granulosa cells of growing follicles in fresh and vitrified tissues. Secondary follicles from fresh tissues (70 ± 12%) and tissues vitrified with VEG (52 ± 2%) showed similar survival rates (all data: mean ± SEM; P > 0.05). For both groups, the initial follicle diameter was similar and increased (P < 0.05) by Week 3, but diameters in vitrified follicles were smaller (P < 0.05) by Week 6 (566 ± 27 µm) than those of the fresh follicles (757 ± 26 µm). Antrum formation rates were lower (P < 0.05) for vitrified (37 ± 6%) relative to fresh (64 ± 8%) follicles. There was no significant change in levels in culture media of E2, P4 and A4 between fresh and VEG groups at any time point during culture.
LIMITATIONS, REASONS FOR CAUTION
Only in vitro studies are reported. Future in vivo tissue transplantation studies will be needed to confirm long-term function and fertility potential of vitrified ovarian tissues.
WIDER IMPLICATIONS OF THE FINDINGS
This is the first demonstration of antral follicle development during 3D culture following ovarian tissue vitrification in a closed system using primate ovarian tissue. While diminished antrum formation and slower growth in vitro reflect residual cryodamage, continued development of ovarian tissue vitrification based on cryobiology principles using a non-human primate model will identify safe, practical and efficient protocols for eventual clinical use. Tissue function following heterotopic transplantation is currently being examined.
STUDY FUNDING/COMPETING INTEREST(S)
National Institutes of Health (NIH) Oncofertility Consortium UL1 RR024926 (1RL1-HD058293, HD058295, PL1 EB008542), the Eunice Kennedy Shriver NICHD/NIH (U54 HD018185) and ONPRC 8P51OD011092-53. G.M.F. works for the company that makes the polymers used in the current study.
Larvae of the freeze-avoiding beetle Cucujus clavipes puniceus (Coleoptera: Cucujidae) in Alaska have mean supercooling points in winter of -35 to -42 degrees C, with the lowest supercooling point ...recorded for an individual of -58 degrees C. We previously noted that some larvae did not freeze when cooled to -80 degrees C, and we speculated that these larvae vitrified. Here we present evidence through differential scanning calorimetry that C. c. puniceus larvae transition into a glass-like state at temperatures<-58 degrees C and can avoid freezing to at least -150 degrees C. This novel finding adds vitrification to the list of insect overwintering strategies. While overwintering beneath the bark of fallen trees, C. c. puniceus larvae may experience low ambient temperatures of around -40 degrees C (and lower) when microhabitat is un-insulated because of low snow cover. Decreasing temperatures in winter are correlated with loss of body water from summer high levels near 2.0 to winter lows near 0.4 mg mg(-1) dry mass and concomitant increases in glycerol concentrations (4-6 mol l(-1)) and thermal hysteresis. Finally, we provide direct evidence that Cucujus from Wiseman, Alaska, survive temperatures to -100 degrees C.
Vitrification as a means of cryopreservation has become a standard approach for oocytes from livestock. This paradigm shift occurred primarily as a result of the demonstration in 1996 that bovine ...oocytes are extremely susceptible to chilling injury. Since that early work, numerous devices have been used as supports for oocytes during so-called “ultra-rapid cooling”, and occasionally, trials involving the deposition of small volumes of media containing oocytes directly into liquid nitrogen to facilitate cooling have been reported. Results reporting blastocyst development exceeding 10% are common, but variability remains high, and a standard method for bovine oocytes remains to be established. Oocytes from pigs are particularly difficult to cryopreserve, even with the use of ultrarapid cooling approaches. Few reports have demonstrated blastocyst development exceeding 5%. The application of hydrostatic pressure before vitrification appears to impart stress tolerance to porcine oocytes, as the results of some treatments have shown development to blastocysts at proportions >10%. Work on sheep oocyte vitrification is relatively new, and a few articles have reported blastocyst development at 10% or more. Messenger RNA levels are reportedly altered in sheep oocytes as a result of vitrification, and damage to the cytoskeleton is common across species.
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