Trans-nasal Humidified Rapid Insufflation Ventilatory Exchange (THRIVE) and its Utility in Otolaryngology, Head and Neck Surgery: A Literature Review.

High-flow nasal oxygen (HFNO) therapy is extensively used in critical care units for spontaneously breathing patients. Trans-nasal humidified rapid insufflation ventilatory exchange (THRIVE) is a method of apnoeic oxygenation with continuous nasal delivery of warmed, humidified oxygen at high-flow rates up to 70L/min. THRIVE extends the apnoeic window before desaturation occurs so that tubeless anaesthesia is possible. The advent of THRIVE has had a monumental impact on anaesthetic practice, with a diverse range of clinical applications and it has been incorporated into difficult airway guidelines. THRIVE has many applications in otolaryngology and head and neck surgery. It is used as a pre-oxygenation tool during induction in both anticipated and unanticipated difficult airway scenarios and as a method of oxygenation for tubeless anaesthesia in elective laryngotracheal and hypopharyngeal surgeries and during emergence from anaesthesia. In this scoping review of the literature, we aim to provide an overview on the utility of THRIVE in otolaryngology, including the underlying physiologic principles, current indications and limitations, and its feasibility and safety in different surgical contexts and specific population groups.

Durable transgene expression and efficient re-administration after rAAV2.5T-mediated fCFTRΔR gene delivery to adult ferret lungs.

The dosing interval for effective recombinant adeno-associated virus (rAAV)-mediated gene therapy of cystic fibrosis lung disease remains unknown. Here, we assessed the durability of rAAV2.5T-fCFTRΔR-mediated transgene expression and neutralizing antibody (NAb) responses in lungs of adult wild-type ferrets. Within the first 3 months following rAAV2.5T-fCFTRΔR delivery to the lung, CFTRΔR transgene expression declined ∼5.6-fold and then remained stable to 5 months at ∼26% the level of endogenous CFTR. rAAV NAbs in the plasma and bronchoalveolar lavage fluid (BALF) peaked at 21 days, coinciding with peak ELISpot T cell responses to AAV capsid peptides, after which both responses declined and remained stable at 4-5 months post dosing. Administration of reporter vector rAAV2.5T-gLuc (gaussia luciferase) at 5 months following rAAV2.5T-fCFTRΔR dosing gave rise to similar levels of gLuc expression in the BALF as observed in age-matched reporter-only controls, demonstrating that residual BALF NAbs were functionally insignificant. Notably, the second vector administration led to a 2.6-fold greater ELISpot T cell response and ∼2.3-fold decline in fCFTRΔR mRNA and vector genomes derived from the initial rAAV2.5T-fCFTRΔR administration, suggesting selective destruction of transduced cells from the first vector dose. These findings provide insights into humoral and cellular immune response to rAAV that may be useful for optimizing gene therapy to the cystic fibrosis lung.

Early Results in Total Replacement of the Distal Radioulnar Joint.

BACKGROUND: Pathology of the distal radioulnar joint (DRUJ) including instability and arthritis presents a challenge for hand and upper extremity surgeons. Surgical options include a Darrach procedure and similar resections, soft tissue interposition arthroplasty, and a one-bone forearm. In 2005, a prosthesis for DRUJ arthroplasty was approved for use in the United States. The authors hypothesize that DRUJ arthroplasty will lead to improved pain and range of motion (ROM) with a moderate, but manageable, complication rate. METHODS: A retrospective review of 46 patients who underwent DRUJ arthroplasty by a single private group of hand surgeons was performed. Demographics, complications, postoperative visual analog scale (VAS), and postoperative ROM were obtained and analyzed. RESULTS: The patients were followed up for a mean of 60 weeks. The implant was used both as primary surgical treatment for DRUJ pathology and as salvage for previous failed procedures. Twenty-two percent of patients experienced complications: 15% required revision surgery. No patients were converted to another type of implant, including those who underwent revision surgery. Prominent hardware was the most common indication requiring revision. Patients achieved an improvement in supination of 17° and extension of 5°. They additionally achieved a decrease in average VAS score from 7.1 to 2.3. CONCLUSIONS: Distal radioulnar joint arthroplasty reduces pain and improves ROM in patients with DRUJ pathology with a 22% complication rate. This cohort demonstrates improved pain, modest improvement in ROM, but a 22% complication rate for this implant. Further long-term studies are encouraged.

Perceptions of Wild Pig Impact, Management, and Policy in Alabama.

Successful management of invasive species often requires working across public and private landownerships. A prime example of an invasive species that commonly occurs on privately and publicly owned and managed lands is the wild pig (Sus scrofa). Because of the multitude of negative impacts associated with wild pigs, management must occur across both private and public lands to achieve widespread control and sustained success. However, managing wild pigs across property boundaries is challenging as we know very little about differing management practices and landowner perspectives. To address this knowledge gap, we sought to understand wild pig management efforts on privately owned lands, the perceived economic, ecological, and human health impact of wild pigs, and beliefs related to policy. Generally, stakeholders believe wild pigs have negative impacts on wildlife, the economy, and ecological and public health, however less than half of landowners participate in wild pig control. Furthermore, stakeholders believe that the responsibility of managing and paying for damages associated with wild pigs lies with individual landowners. Our findings suggest that increased efficacy of wild pig control and collaboration between private and public landowners is not only possible but also necessary if wild pig population control is to be regionally successful.

Does type of bone graft matter? A retrospective review of the use of biological bone grafts in patients undergoing elective 1-3 level spinal interbody fusion.

OBJECTIVE: There is a lack of strong evidence for use of expensive bone substitutes. This study compares perioperative data and patient reported quality-of-life outcomes across the varied types of bone graft extenders. The study analyzes the existing Quality and Outcomes Database and evaluates patient reported outcomes for 1-3 level lumbar fusion procedures comparing across different types of biologics bone graft. METHODS: We retrospectively analyzed a prospectively collected data registry. Bone graft implant data were collected and grouped into the following categories: (1) Autograft with basic allograft (2) Enhanced, synthetic, or cellular allograft (3) Use of BMP. Preoperative and 1 year patient reported outcomes and perioperative data from the prospective collected registry were analyzed. RESULTS: There were 384 patients included in this study. There were 168 (43.8%) patients in group 1, 133 (34.6%) patients in group 2, and 83 (21.6%) in group 3. There were no group differences in baseline or 1 year back pain, leg pain, ODI, or EQ-5D. The GLM Repeated Measures results indicate a significant difference within each of the three groups between the preoperative and postoperative measures for back pain, leg pain, ODI, and EQ-5D. The change over time was not significantly different between the groups. CONCLUSIONS: Bone graft extenders are a significant contributor to the cost of lumbar fusion. This study demonstrates no difference in preoperative, and 1 year patient reported outcomes between the three groups. There was no significant difference in rate of reoperations across the three groups.

Preoperative Anemia and Postoperative Outcomes in Cardiac Surgery: A Mediation Analysis Evaluating Intraoperative Transfusion Exposures.

BACKGROUND: Preoperative anemia is associated with adverse outcomes in cardiac surgery, yet it remains unclear what proportion of this association is mediated through red blood cell (RBC) transfusions. METHODS: This is a historical observational cohort study of adults undergoing coronary artery bypass grafting or valve surgery on cardiopulmonary bypass at an academic medical center between May 1, 2008, and May 1, 2018. A mediation analysis framework was used to evaluate the associations between preoperative anemia and postoperative outcomes, including a primary outcome of acute kidney injury (AKI). Intraoperative RBC transfusions were evaluated as mediators of preoperative anemia and outcome relationships. The estimated total effect, average direct effect of preoperative anemia, and percent of the total effect mediated through transfusions are presented with 95% confidence intervals and P -values. RESULTS: A total of 4117 patients were included, including 1234 (30%) with preoperative anemia. Overall, 437 of 4117 (11%) patients went on to develop AKI, with a greater proportion of patients having preoperative anemia (219 of 1234 [18%] vs 218 of 2883 [8%]). In multivariable analyses, the presence of preoperative anemia was associated with increased postoperative AKI (6.4% [4.2%-8.7%] absolute difference in percent with AKI, P < .001), with incremental decreases in preoperative hemoglobin concentrations displaying greater AKI risk (eg, 11.9% [6.9%-17.5%] absolute increase in probability of AKI for preoperative hemoglobin of 9 g/dL compared to a reference of 14 g/dL, P < .001). The association between preoperative anemia and postoperative AKI was primarily due to direct effects of preoperative anemia (5.9% [3.6%-8.3%] absolute difference, P < .001) rather than mediated through intraoperative RBC transfusions (7.5% [-4.3% to 21.1%] of the total effect mediated by transfusions, P = .220). Preoperative anemia was also associated with longer hospital durations (1.07 [1.05-1.10] ratio of geometric mean length of stay, P < .001). Of this total effect, 38% (22%, 62%; P < .001) was estimated to be mediated through subsequent intraoperative RBC transfusion. Preoperative anemia was not associated with reoperation or vascular complications. CONCLUSIONS: Preoperative anemia was associated with higher odds of AKI and longer hospitalizations in cardiac surgery. The attributable effects of anemia and transfusion on postoperative complications are likely to differ across outcomes. Future studies are necessary to further evaluate mechanisms of anemia-associated postoperative organ injury and treatment strategies.

Return to Sports and Recreational Activities Following Arthroplasty of the Basal Joint of the Thumb: A Retrospective Review.

Purpose: Arthroplasty of the basal, or carpometacarpal, joint of the thumb has been shown to decrease pain, improve strength, improve range of motion, and allow return to work. This study sought to assess whether basal joint arthroplasty also allows for a return to sports and recreational activities. Methods: A survey assessing participation in sports and recreational activities, timing of return to play after surgery, enjoyment, and the presence of pain and limitations was mailed to patients who had undergone an arthroplasty of the basal joint of the thumb over a 3-year period. Results: Of the 333 patients who underwent thumb carpometacarpal arthroplasty, met the criteria, and responded, 73% were able to successfully return to sports and recreational activities, with decreased pain and at the same or increased level of play, frequency of participation, and level of enjoyment for their sport or recreational activity. Patients were more likely to successfully return to sports and recreational activities if they had undergone surgery on their nondominant hand, did not stop their sport or recreational activity before surgery, were able to return within 9 months of surgery, and reported no postoperative limitations. Successful return to sports and recreational activities was not related to age, sex, surgeon, level of play, or the type of sport or recreational activity. Conclusions: Most patients who replied to our survey reported successful return to sports and recreational activities after arthroplasty of the basal joint of the thumb. Type of study/level of evidence: Prognostic IV.

Synthesis and cluster structure distortions of biscarborane dithiol, thioether, and disulfide.

The synthesis and structural characterization of the first sulfur-containing derivatives of the C,C-biscarborane {ortho-C2B10}2 cluster - thiol, thioether, and disulfide - are reported. The biscarboranyl dithiol (1-HS-C2B10H10)2 exhibits an exceedingly long intracluster carbon-carbon bond length of 1.858(3) Å, which is attributed to the extensive interaction between the lone pairs of the thiol groups and the unoccupied molecular orbital of the carborane cluster. The structures of the doubly deprotonated biscarboranyl dithiolate anion (1-S-C2B10H10)22- with various counter cations feature an even longer carbon-carbon bond length of 2.062(10) Å within the cluster along with a short carbon-sulfur bond of 1.660(7) Å, both indicative of significant delocalization of electron density from the sulfur atoms into the cluster.

Land cover changes across Greenland dominated by a doubling of vegetation in three decades.

Land cover responses to climate change must be quantified for understanding Arctic climate, managing Arctic water resources, maintaining the health and livelihoods of Arctic societies and for sustainable economic development. This need is especially pressing in Greenland, where climate changes are amongst the most pronounced of anywhere in the Arctic. Ice loss from the Greenland Ice Sheet and from glaciers and ice caps has increased since the 1980s and consequently the proglacial parts of Greenland have expanded rapidly. Here we determine proglacial land cover changes at 30 m spatial resolution across Greenland during the last three decades. Besides the vastly decreased ice cover (- 28,707 km2 ± 9767 km2), we find a doubling in total areal coverage of vegetation (111% ± 13%), a quadrupling in wetlands coverage (380% ± 29%), increased meltwater (15% ± 15%), decreased bare bedrock (- 16% ± 4%) and increased coverage of fine unconsolidated sediment (4% ± 13%). We identify that land cover change is strongly associated with the difference in the number of positive degree days, especially above 6 °C between the 1980s and the present day. Contrastingly, absolute temperature increase has a negligible association with land cover change. We explain that these land cover changes represent local rapid and intense geomorphological activity that has profound consequences for land surface albedo, greenhouse gas emissions, landscape stability and sediment delivery, and biogeochemical processes.

Effect of fasedienol (PH94B) pherine nasal spray and steroidal hormones on electrogram responses and autonomic nervous system activity in healthy adult volunteers.

OBJECTIVE: Fasedienol (PH94B) is a pherine compound formulated as a nasal spray that is hypothesized to regulate olfactory-amygdala circuits of fear and anxiety. Fasedienol's effect on the local electrogram of nasal chemosensory neurons (EGNR) and autonomic nervous system (ANS) responses versus steroidal hormones and controls in healthy adults is reported. METHODS: Eight males and 8 females randomly received aerosolized control (propylene glycol) and study drugs (fasedienol, 17ß-estradiol, progesterone, cortisol, and testosterone, 0.4 µg each in propylene glycol) onto the nasal septum mucosal lining at 30-min intervals over 2 sessions. EGNR was continuously monitored; autonomic parameters were recorded before and after administration. RESULTS: Fasedienol significantly increased EGNR amplitude (males: 5.0 vs. 0.6 mV, p < 0.001; females:5.7 vs. 0.6 mV, p < 0.001), and rapidly reduced respiratory rate (p < 0.05), heart rate (p < 0.01), and electrodermal activity (p < 0.05) versus control. EGNR and ANS responses after steroidal hormone administration were similar to control. 81% reported feeling less tense/more relaxed after receiving fasedienol, but not after receiving either control or steroidal hormones. CONCLUSIONS: Intranasal fasedienol, but not control or steroidal hormones, activated EGNR and rapidly reduced ANS responses, consistent with sympatholytic effects. Combined with subjective reports, results suggest fasedienol may provide acute relief in anxiety conditions.

A Technique to Enable Efficient Adaptive Radiation Therapy: Automated Contouring of Prostate and Adjacent Organs.

Purpose: The purpose of this work was to investigate the use of a segmentation approach that could potentially improve the speed and reproducibility of contouring during magnetic resonance-guided adaptive radiation therapy. Methods and Materials: The segmentation algorithm was based on a hybrid deep neural network and graph optimization approach that also allows rapid user intervention (Deep layered optimal graph image segmentation of multiple objects and surfaces [LOGISMOS] + just enough interaction [JEI]). A total of 115 magnetic resonance-data sets were used for training and quantitative assessment. Expert segmentations were used as the independent standard for the prostate, seminal vesicles, bladder, rectum, and femoral heads for all 115 data sets. In addition, 3 independent radiation oncologists contoured the prostate, seminal vesicles, and rectum for a subset of patients such that the interobserver variability could be quantified. Consensus contours were then generated from these independent contours using a simultaneous truth and performance level estimation approach, and the deviation of Deep LOGISMOS + JEI contours to the consensus contours was evaluated and compared with the interobserver variability. Results: The absolute accuracy of Deep LOGISMOS + JEI generated contours was evaluated using median absolute surface-to-surface distance which ranged from a minimum of 0.20 mm for the bladder to a maximum of 0.93 mm for the prostate compared with the independent standard across all data sets. The median relative surface-to-surface distance was less than 0.17 mm for all organs, indicating that the Deep LOGISMOS + JEI algorithm did not exhibit a systematic under- or oversegmentation. Interobserver variability testing yielded a mean absolute surface-to-surface distance of 0.93, 1.04, and 0.81 mm for the prostate, seminal vesicles, and rectum, respectively. In comparison, the deviation of Deep LOGISMOS + JEI from consensus simultaneous truth and performance level estimation contours was 0.57, 0.64, and 0.55 mm for the same organs. On average, the Deep LOGISMOS algorithm took less than 26 seconds for contour segmentation. Conclusions: Deep LOGISMOS + JEI segmentation efficiently generated clinically acceptable prostate and normal tissue contours, potentially limiting the need for time intensive manual contouring with each fraction.

Role of Transporters and Enzymes in Metabolism and Distribution of 4-Chlorokynurenine (AV-101).

4-Chlorokynurenine (4-Cl-KYN, AV-101) is a prodrug of a NMDA receptor antagonist and is in clinical development for potential CNS indications. We sought to further understand the distribution and metabolism of 4-Cl-KYN, as this information might provide a strategy to enhance the clinical development of this drug. We used excretion studies in rats, in vitro transporter assays, and pharmacogenetic analysis of clinical trial data to determine how 4-Cl-KYN and metabolites are distributed. Our data indicated that a novel acetylated metabolite (N-acetyl-4-Cl-KYN) did not affect the uptake of 4-Cl-KYN across the blood-brain barrier via LAT1. 4-Cl-KYN and its metabolites were found to be renally excreted in rodents. In addition, we found that N-acetyl-4-Cl-KYN inhibited renal and hepatic transporters involved in excretion. Thus, this metabolite has the potential to limit the excretion of a range of compounds. Our pharmacogenetic analysis found that a SNP in N-acetyltransferase 8 (NAT8, rs13538) was linked to levels of N-acetyl-4-Cl-KYN relative to 4-Cl-KYN found in the plasma and that a SNP in SLC7A5 (rs28582913) was associated with the plasma levels of the active metabolite, 7-Cl-KYNA. Thus, we have a pharmacogenetics-based association for plasma drug level that could aid in the drug development of 4-Cl-KYN and have investigated the interaction of a novel metabolite with drug transporters.

Deep Parasternal Intercostal Plane Block for Postoperative Analgesia After Sternotomy for Cardiac Surgery-A Retrospective Cohort Study.

OBJECTIVE: To examine the analgesic efficacy of postoperative deep parasternal intercostal plane (DPIP) blocks for patients having cardiac surgery via median sternotomy. DESIGN: This single-center retrospective study compared patients receiving bilateral DPIP blocks with a matched cohort of patients not receiving DPIP blocks. SETTING: Large quaternary referral center. PARTICIPANTS: Adult patients admitted to the authors' institution from January 1, 2016, to August 14, 2020, for elective cardiac surgery via median sternotomy. INTERVENTIONS: Patients received ultrasound-guided bilateral DPIP blocks. MEASUREMENTS AND MAIN RESULTS: A total of 113 patients received a DPIP block; 3,461 patients did not. The estimated multiplicative change in cumulative opioid consumption through 24 hours was 0.42 (95% CI 0.32-0.56; p < 0.001), indicating that patients receiving DPIP blocks required 60% fewer opioids than patients who did not. Proportional odds ratios for the average pain score on postoperative day (POD) 0 was 0.46 (95% CI 0.32-0.65; p < 0.001), and POD 1 was 0.67 (95% CI 0.47-0.94; p = 0.021), indicating lower pain scores for patients receiving blocks. The exploratory analysis identified an inverse correlation between DPIP blocks and atrial fibrillation incidence (2% v 15%; inverse probability of treatment weighting odds ratio 0.088, 95% CI 0.02-0.41; p = 0.002). CONCLUSIONS: The use of DPIP blocks in patients undergoing cardiac surgery via median sternotomy was associated with less opioid use and improved pain scores in the early postoperative period compared with patients not receiving blocks. Prospective randomized controlled studies should further elucidate the efficacy and risks of DPIP blocks in cardiac surgery.

Magnetic Resonance Imaging of Iron Metabolism with T2* Mapping Predicts an Enhanced Clinical Response to Pharmacologic Ascorbate in Patients with GBM.

PURPOSE: Pharmacologic ascorbate (P-AscH-) is hypothesized to be an iron (Fe)-dependent tumor-specific adjuvant to chemoradiation in treating glioblastoma (GBM). This study determined the efficacy of combining P-AscH- with radiation and temozolomide in a phase II clinical trial while simultaneously investigating a mechanism-based, noninvasive biomarker in T2* mapping to predict GBM response to P-AscH- in humans. PATIENTS AND METHODS: The single-arm phase II clinical trial (NCT02344355) enrolled 55 subjects, with analysis performed 12 months following the completion of treatment. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method and compared across patient subgroups with log-rank tests. Forty-nine of 55 subjects were evaluated using T2*-based MRI to assess its utility as an Fe-dependent biomarker. RESULTS: Median OS was estimated to be 19.6 months [90% confidence interval (CI), 15.7-26.5 months], a statistically significant increase compared with historic control patients (14.6 months). Subjects with initial T2* relaxation < 50 ms were associated with a significant increase in PFS compared with T2*-high subjects (11.2 months vs. 5.7 months, P < 0.05) and a trend toward increased OS (26.5 months vs. 17.5 months). These results were validated in preclinical in vitro and in vivo model systems. CONCLUSIONS: P-AscH- combined with temozolomide and radiotherapy has the potential to significantly enhance GBM survival. T2*-based MRI assessment of tumor iron content is a prognostic biomarker for GBM clinical outcomes. See related commentary by Nabavizadeh and Bagley, p. 255.

Commissurotomy Using Carbon Dioxide Laser in 67 Dogs.

Commissurotomy is a surgical technique whereby the lip commissure is incised. Indications for commissurotomy include cheiloplasty, partial commissurectomy, or access to the caudal portion of the maxilla or mandible for oral surgery. Carbon dioxide (CO2) laser was used for commissurotomy in dogs for partial commissurectomy (n = 7) or access for oral surgery (n = 60). All dogs had oral or maxillofacial neoplasms that required resective surgery. The CO2 laser was used to perform commissurotomy or commissurectomy, as indicated. Commissurotomy healing was evaluated at 2 weeks with longer-term follow-up of a minimum of 6 weeks (104.6 ± 99.2 weeks) postoperatively. Postoperative complications related to commissurotomy (n = 6) included mucosal dehiscence (n = 3) less than 1.5 cm, lip margin dehiscence (n = 2) less than 1.0 cm, and complete commissurotomy wound dehiscence (n = 1). Two wound dehiscence cases, including the complete wound dehiscence, had uncomplicated healing following revision surgery. Minor marginal and mucosal dehiscence cases healed by the second intention. Periwound edema ranged from mild to severe and resolved by the 2-week postoperative examination. Statistical analysis showed that complications associated with commissurotomy/commissurectomy were independent of the type of surgical procedure, tumor type, and surgical margin evaluation when using the CO2 laser. Commissurotomy using CO2 laser provided rapid and unimpeded exposure with minimal hemorrhage of the caudal maxilla and mandible for resective oral and maxillofacial surgery.

The effects of gonadal hormones on heroin Self-Administration in male gonadectomized rats.

RATIONALE: Previous studies have shown that gonadal hormones influence opioid self-administration in female rodents, but very few studies have examined these effects in male rodents. OBJECTIVES: The purpose of this study was to examine the effects of chronic hormone treatment on intravenous heroin self-administration in gonadectomized male rats using both physiological and supraphysiological doses of testosterone, estradiol, or progesterone. METHODS: Gonadectomized male rats were surgically implanted with intravenous catheters and trained to self-administer heroin on a fixed ratio (FR1) schedule of reinforcement. Using a between-subjects design, rats were treated daily with testosterone (0.175 or 1.75 mg, sc), estradiol (0.0005 or 0.005 mg, sc), progesterone, (0.0125 or 0.125 mg, sc), or their vehicles. After 14 days of chronic treatment, a dose-effect curve was determined for heroin (0.0003-0.03 mg/kg/infusion) over the course of one week. RESULTS: Neither testosterone nor estradiol altered responding maintained by heroin. In contrast, the high dose of progesterone (0.125 mg) reduced responding maintained by all doses of heroin to saline-control levels. This dose of progesterone did not reduce responding maintained by food on a progressive ratio schedule in either food-restricted or food-sated rats. CONCLUSIONS: These data indicate that exogenous progesterone or a pharmacologically active metabolite selectively decreases heroin intake in male rodents, which may have therapeutic implications for men with opioid use disorder.

Impact of Share 35 liver transplantation allocation in Australia and New Zealand.

Patients with high model for end-stage liver disease (MELD) scores waiting for liver transplantation in Australia and New Zealand (ANZ) have had limited access to deceased donor livers and therefore binational sharing of livers, for patients with a MELD score ≥35 was introduced in February 2016. Waiting list mortality, post-transplant outcomes and intention-to-treat survival were compared between patients whose MELD score reached 35 on the waiting list between October 2013 and April 2015 (Pre-Share 35 group, n = 23) and patients who were Share 35 listed between February 2016 and May 2022 (Share 35 group, n = 112). There was significantly reduced waiting list mortality in share 35 listed patients in comparison to the pre-Share 35 group (11.7% vs. 52.2%, OR .120 95% CI .044-.328, P < .001). Post-transplant patient and graft survival were not significantly different between the groups (5-year patient survival 82% vs. 84%, P = .991, 5-year graft survival 82% vs. 76%, P = .543). Intention-to-treat survival was superior in the Share 35 group (HR .302, 95% CI .149-.614, P < .001). Introduction of Share 35 in ANZ resulted in a 78% risk reduction in waiting list mortality, equivalent post-transplant survival and an improvement in intention-to-treat survival.

The Full Continuum of Robotic Breast Surgery: Robotic-assisted Mastectomy, Robotic DIEP Flap, and Robotic Supermicrosurgery.

In recent years, robotic surgery has rapidly expanded to improve surgical outcomes in a variety of surgical subspecialties. Although plastic surgery has taken longer to integrate robotic surgery into practice, the advantages of robotic-assisted surgery, including improved visualization and resolution, minimally invasive approaches, and the ability to surpass human precision and scale, have driven its more recent adoption into plastic surgery. Currently, procedures performed with robotic assistance that are considered part of the continuum of surgical treatment of breast cancer include robotic-assisted nipple-sparing mastectomy, reconstruction with the robotic latissimus dorsi flap or the deep inferior epigastric artery perforator flap, and robotic microsurgery for the flap anastomosis and/or the surgical treatment of lymphedema. The authors provide an overview of robotic surgery and how it has been integrated into the field of plastic surgery, as well as a review of the most common procedures within the field where robotic assistance can be incorporated: nipple-sparing mastectomy, robotic latissimus flap, robotic deep inferior epigastric artery perforator flap breast reconstruction, and microvascular anastomoses.

Estradiol and Mu opioid-mediated reward: The role of estrogen receptors in opioid use.

Opioid use and opioid use disorder are characterized by sex and gender differences, and some of these differences may be mediated by differences in the hormonal milieu within and across individuals. This review focuses on the role of ovarian hormones, and particularly estradiol, on the endogenous mu opioid receptor system. There is an abundance of data indicating that estradiol influences the activity of endogenous mu opioid peptides, the activation of mu opioid receptors, and the internalization and desensitization of mu opioid receptors. These effects have functional consequences on behaviors mediated by endogenous mu opioid receptor activity and on sensitivity to mu opioid agonists and antagonists. Recent behavioral data suggest these consequences extend to mu opioid reward, and preclinical studies report that estradiol decreases self-administration of mu opioid receptor agonists across a range of experimental conditions. Data collected in human laboratory studies suggest that estradiol may have functionally similar effects in clinical populations, and thus estrogen receptors may be a potential target in the development of novel therapeutics. This review summarizes data from cellular assays to clinical trials to explore how estradiol influences mu opioid receptor activity, as well as potential ways in which estrogen receptors may be targeted to address the problems of opioid use.