Multikinase Networks: Two-Component Signaling Networks Integrating Multiple Stimuli.

Bacteria depend on two-component systems to detect and respond to threats. Simple pathways comprise a single sensor kinase (SK) that detects a signal and activates a response regulator protein to mediate an appropriate output. These simple pathways with only a single SK are not well suited to making complex decisions where multiple different stimuli need to be evaluated. A recently emerging theme is the existence of multikinase networks (MKNs) where multiple SKs collaborate to detect and integrate numerous different signals to regulate a major lifestyle switch, e.g., between virulence, sporulation, biofilm formation, and cell division. In this review, the role of MKNs and the phosphosignaling mechanisms underpinning their signal integration and decision making are explored.

Postanesthesia Care Unit and Anesthetic Management Outcomes Among Patients Undergoing Noncardiac Surgery: Differences by Race and Ethnicity.

PURPOSE: To investigate the association of patient race and ethnicity with postanesthesia care unit (PACU) outcomes in common, noncardiac surgeries requiring general anesthesia. DESIGN: Single tertiary care academic medical center retrospective matched cohort. METHODS: We matched 1:1 1836 adult patients by race and/or ethnicity undergoing common surgeries. We compared racial and ethnic minority populations (62 American Indian, 250 Asian, 315 Black or African American, 281 Hispanic, and 10 Pacific Islander patients) to 918 non-Hispanic White patients. The primary outcomes were: the use of an appropriate number of postoperative nausea and vomiting (PONV) prophylactics; the incidence of PONV; and the use of a propofol infusion as part of the anesthetic (PROP). Secondary outcomes were: the use of opioid-sparing multimodal analgesia, including the use of regional anesthesia for postoperative pain control; the use of any local anesthetic, including the use of liposomal bupivacaine; the duration until readiness for discharge from the PACU; the time between arrival to PACU and first pain score; and the time between the first PACU pain score of ≥4 and administration of an analgesic. Logistic and linear regression were used for relevant outcomes of interest. FINDINGS: Overall, there were no differences in the appropriate number of PONV prophylactics, nor the incidence of PONV between the two groups. There was, however, a decreased use of PROP (OR = 0.80; 95% CI: 0.69, 0.94; P = .005), PACU length of stay was 9.56 minutes longer (95% CI: 2.62, 16.49; P = .007), and time between arrival to PACU and first pain score was 2.30 minutes longer in patients from racial and ethnic minority populations (95% CI: 0.99, 3.61; P = .001). There were no statistically significant differences in the other secondary outcomes. CONCLUSIONS: The rate of appropriate number of PONV prophylactic medications as well as the incidence of PONV were similar in patients from racial and ethnic minority populations compared to non-Hispanic White patients. However, there was a lower use of PROP in racial and ethnic minority patients. It is important to have a health equity lens to identify differences in management that may contribute to disparities within each phase of perioperative care.

Aortic Stenosis Associated with an Increase in Mortality in Surgical Hip Fracture Patients.

OBJECTIVES: The majority of hip fracture patients in the United States are older adult patients with multiple comorbidities. Aortic stenosis (AS) in older adult patients with traumatic hip fracture is not uncommon. This study investigated the association between AS and postoperative mortality and serious complications. METHODS: In this retrospective cohort study, a chart review was performed of patients with AS who underwent hip fracture surgical repair between January 2011 and December 2019 within one health system. A control group of hip fracture patients without AS was identified and matched based on body mass index, age, sex, date of surgery and Charlson Comorbidity Index. The primary outcome of interest was 90-day mortality; secondary outcomes included 30-day postoperative complications, intensive care unit admission (ICU), and hospital length of stay. RESULTS: In total, 146 hip fracture patients with AS and 146 without AS were identified. In the AS group, there was an increased odds of 90-day mortality (odds ratio 2.64, 95% confidence interval 1.32-5.28, P = 0.005), and an increased odds of ICU admission (odds ratio 3.00, 95% confidence interval 1.36-6.68, P = 0.004). CONCLUSIONS: The presence of AS was independently associated with an increase in 90-day mortality and postoperative ICU stay in patients undergoing surgical repair of a hip fracture.

Racial Disparities in the Use of Peripheral Nerve Blocks for Postoperative Analgesia After Total Mastectomy: A Retrospective Cohort Study.

BACKGROUND: Peripheral nerve blocks (PNBs) are used to provide postoperative analgesia after total mastectomy. PNBs improve patient satisfaction and decrease postoperative opioid use, nausea, and vomiting. Few studies have examined whether there is racial-ethnic disparity in the use of PNBs for patients having total mastectomy. We hypothesized that non-Hispanic Asian, non-Hispanic Black, non-Hispanic patients of other races, and Hispanic patients would be less likely to receive a PNB for postoperative analgesia compared to non-Hispanic White patients having total mastectomy. Secondarily, we hypothesized that PNBs would be associated with reduced odds of major complications after total mastectomy. METHODS: We performed a retrospective cohort study using National Surgical Quality Improvement Program (NSQIP) data from 2015 to 2019. Patients were included if they underwent total mastectomy under general anesthesia. Unadjusted rates of PNB use were compared between race-ethnicity groups. Multivariable logistic regression was performed to determine whether race-ethnicity group was independently associated with receipt of a PNB for postoperative analgesia. Secondarily, we calculated crude and risk-adjusted odds ratios for major complications in patients who received a PNB. RESULTS: There were 64,103 patients who underwent total mastectomy and 4704 (7.3%) received a PNB for postoperative analgesia. Patients who received a PNB were younger, more commonly women, were less likely to have diabetes and hypertension, and had less disseminated cancer (all P < .05). In our regression analysis, the odds of receiving a PNB differed significantly by race-ethnicity group (P < .001). Non-Hispanic Asian and non-Hispanic Black patients had reduced odds of receiving a PNB compared to non-Hispanic White patients (odds ratio [OR], 0.41; 95% confidence interval [CI], 0.33-0.49 and OR, 0.37 [0.32-0.44]), respectively. Non-Hispanic patients of other races, including American Indian, Alaskan Native, and Pacific Islander, also had reduced odds of receiving a PNB (OR, 0.73 [95% CI, 0.64-0.84]) compared to non-Hispanic White patients, as did Hispanic patients (OR, 0.62 [0.56-0.69]). Patients who received a PNB did not have reduced odds of major complications after mastectomy (crude OR, 0.83 [0.65-1.08]; P = .17 and adjusted OR, 0.85 [0.65-1.10]; P = .21). CONCLUSIONS: Significant disparity exists in the use of PNBs for postoperative analgesia in patients of different race-ethnicity who undergo total mastectomy in the United States. Continued efforts are needed to better understand the causes of disparity and to ensure equitable access to PNBs.

Development, Validation, and Results of a Survey of Personal Electronic Device Use Among 299 Anesthesia Providers From a Single Institution.

BACKGROUND: The pattern of perioperative use of personal electronic devices (PEDs) among anesthesia providers in the United States is unknown. METHODS: We developed a 31-question anonymous survey of perioperative PED use that was sent to 813 anesthesiologists, anesthesiology residents, and certified registered nurse anesthetists at 3 sites within one health system. The electronic survey assessed patterns of PED use inside the operating room (OR), outside the OR, and observed in others. Questions were designed to explore the various purposes for PED use, the potential impact of specific hospital policies or awareness of medicolegal risk on PED use, and whether PED was a source of perioperative distraction. RESULTS: The overall survey response rate was 36.8% (n = 299). With regard to often/frequent PED activity inside the OR, 24% reported texting, 5% reported talking on the phone, and 11% reported browsing on the Internet. With regard to often/frequent PED activity outside the OR, 88% reported texting, 26% reported talking on the phone, and 63% reported browsing the Internet. With regard to often/frequent PED activity observed in others, 52% reported others texting, 14% reported others talking on the phone, and 34% reported others browsing the Internet. Two percent of respondents self-reported a distraction compared to 15% who had observed a distraction in others. Eighty percent of respondents recognized PED as a potential distraction for patient safety. CONCLUSIONS: Our data reinforce that PED use is prevalent among anesthesia providers.

Regional anesthesia in patients with Charcot-Marie-Tooth disease: a historical cohort study of 53 patients.

PURPOSE: Anesthetic management for patients with Charcot-Marie-Tooth disease (CMT) is controversial. Description of the use of regional anesthesia (RA) in patients with CMT is limited. Regional anesthesia has traditionally been avoided because of risk of nerve injury. We retrospectively reviewed patients with CMT who received RA at our institution. METHODS: We performed a historical cohort study of all patients with CMT who received RA from 30 April 2010 to 30 April 2020 within our institution. Charts were reviewed for information on demographics, RA procedures, perioperative variables, evidence of neurologic complications, post-RA neurology consults, and perioperative electromyography (EMG) results. Electromyographs were reviewed by a neurologist who was blinded to the surgical and RA details. RESULTS: Fifty-three patients received a total of 132 regional anesthetics during the study period. Twenty-five patients received RA on more than one occasion. Fifty-five EMGs and 14 postoperative neurology consults were performed. Two patients had neurology consults with peripheral nerve block (PNB) distribution complaints years later. Neither attributed the complaints to the PNB. The other neurology consults were for unrelated complaints. No EMG results suggested injury related to PNB. CONCLUSION: This study found no evidence of documented neurologic complications or an increased risk of nerve injury related to RA in CMT patients.

RéSUMé: OBJECTIF: La prise en charge anesthésique des patients atteints de la maladie de Charcot-Marie-Tooth (CMT) est controversée. Les descriptions de l'utilisation de l'anesthésie régionale (AR) chez les patients atteints de CMT sont limitées. L'anesthésie régionale est traditionnellement évitée en raison du risque de lésion nerveuse. Nous avons rétrospectivement passé en revue les dossiers des patients atteints de CMT ayant reçu une AR dans notre établissement. MéTHODE: Nous avons réalisé une étude de cohorte historique de tous les patients atteints de CMT ayant reçu une AR entre le 30 avril 2010 et le 30 avril 2020 au sein de notre établissement. Les dossiers ont été passés en revue pour en tirer des renseignements sur les données démographiques, les interventions d'AR, les variables périopératoires, les signes de complications neurologiques, les consultations en neurologie post-AR et les résultats de l'électromyographie (EMG) périopératoire. Les électromyographes ont été examinés par un neurologue qui n'avait pas accès aux détails concernant la chirurgie et l'AR. RéSULTATS: Cinquante-trois patients ont reçu un total de 132 anesthésies régionales au cours de la période d'étude. Vingt-cinq patients ont reçu une AR à plus d'une occasion. Cinquante-cinq EMG et 14 consultations postopératoires en neurologie ont été effectuées. Deux patients ont consulté en neurologie après s'être plaints de la distribution du bloc nerveux périphérique (BNP) des années plus tard. Ni l'un ni l'autre n'a attribué ces problèmes au BNP. Les autres consultations en neurologie concernaient des plaintes non liées au BNP. Aucun résultat d'EMG n'a suggéré de lésion liée au BNP. CONCLUSION: Cette étude n'a trouvé aucune preuve de complications neurologiques documentées ou d'un risque accru de lésion nerveuse liée à l'AR chez les patients atteints de CMT.

Impact of a Hemoglobin Trigger Communication Tool on Perioperative Transfusion in Cardiac Surgery.

OBJECTIVES: Blood transfusion represents an important and potentially modifiable risk in the daily practice of cardiac surgery. The risk profile and increasing cost of transfusion led us to study the effect of different maneuvers, interventions, or surgical techniques to minimize transfusion while maintaining patient safety. This study compares postoperative outcomes before and after incorporating a verbal hemoglobin (Hb) trigger during the surgical timeout in which the surgeon and anesthesiologist preemptively agree on a threshold for packed red blood cell (PRBC) administration in the perioperative period. METHODS: The authors performed a chart review of patients who underwent cardiac surgery from July 2013 through June 2014 at our institution. Patients who underwent surgery from July 2013 through December 2013 served as the pre-Hb trigger group, and patients who underwent surgery from January 2014 through June 2014 served as the post-Hb trigger group. Information collected included patient demographics, type of cardiac surgery, preoperative Hb, Hb trigger, and intraoperative and postoperative variables. The primary outcome was the incidence of PRBC transfusions. Secondary outcomes included the incidence of frozen plasma (FP) transfusion, mechanical ventilation beyond postoperative day 1, and 30-day mortality. RESULTS: The study included 191 patients, with 84 in the pre-Hb trigger group and 107 in the post-Hb trigger group. Intraoperative PRBC transfusions did not decrease in the posttrigger group compared with the pretrigger group (pretrigger 51.4% vs posttrigger 52.4%, P = 1.0); however, intraoperative FP administration was lower in the posttrigger group (65.4% vs 50.0%, P = 0.038). Postoperative mechanical ventilation beyond postoperative day 1 also was significantly lower in the posttrigger group compared with the pretrigger group (27.1% vs 14.3%, P = 0.035). CONCLUSIONS: Implementation of a verbal Hb trigger during the surgical timeout was associated with a reduction in FP administration and duration of mechanical ventilation, but not a decrease in PRBC transfusion and mortality.

Intertrochanteric fracture fixation in solid organ transplant patients: outcomes and survivorship.

BACKGROUND: Solid organ transplantation (SOT) recipients have complex medical and surgical risk factors; however, the outcomes of these patients undergoing surgical fixation of hip fractures are unknown. This study sought to evaluate SOT patients' outcomes and survivorship after intertrochanteric (IT) fracture fixation. METHODS: A retrospective review identified 12 SOT patients who underwent cephalomedullary (CMN) nail fixation for IT fractures and were matched (1:2) to a cohort of 24 non-SOT IT fracture patients. Perioperative results and complications, mortality/patient survivorship, and clinical outcomes were compared between the cohorts. RESULTS: The time from presentation to surgical fixation was within 48 h of presentation for the non-SOT patients, while only 75% of SOT patients underwent surgery within 48 h of presentation (p = 0.034). The 90-day readmission rate for SOT patients was 25% versus 13% in the non-SOT group (p = 0.38). Similarly, the SOT cohort experienced a higher rate of major medical complication (25% vs. 13%, p = 0.38). There were two (16%) reoperations in the SOT group and three (13%) in the non-SOT matched group (p = 0.99). Respectively, the 90-day and 1-year estimated patient survivorship was similar between the two cohorts: SOT patients with 92% (95% CI 54-99%) and 73% (95% CI 24-93%) versus 86% (95% CI 62-95%) and 72% (95% CI 47-86%, HR 0.92, 95% CI 0.18-4.62, p = 0.92) in non-SOT patients. CONCLUSION: SOT patients who underwent CMN fixation for IT fractures required more time from hospital presentation to surgical management than non-SOT patients. Although not statistically significant, SOT patients demonstrated more acute complications and readmissions, but similar mortality compared to those without transplant.

A Quality Improvement Project to Decrease Perioperative and Periprocedural Corneal Abrasions.

PURPOSE: We assessed our institution's rate of perioperative and periprocedural corneal abrasions (CAs) and implemented a quality improvement project to improve our detection of CAs and decrease their incidence by at least 25% over 12 months. DESIGN: Retrospective review before and after initiation of a quality improvement project at a single tertiary care institution METHODS: We retrospectively reviewed surgical and procedural patients requiring any type of anesthesia care over three 1-year time periods (2014-2015, 2016-2017, and 2017-2018). Using an electronic pharmacy-based query to identify patients who received proparacaine eye drops in the recovery room, we were able to estimate our incidence of CA during these time periods. We implemented a best practice plan to standardize CA prevention, diagnosis, and treatment after determining our baseline incidence of CA. FINDINGS: Our baseline incidence rate of perioperative and periprocedural CAs was 0.22% (43/19,790 anesthetics) in the 2014-2015 time period. In the 2016-2017 and 2017-2018 time periods, the incidence rate was reduced to 0.09% (21/23,652 anesthetics) and 0.1% (23/23,825 anesthetics), respectively. The use of a standardized CA prevention, diagnosis, and treatment plan reduced the relative risk of CAs by 59% in 2016-2017 (P < .001) and 56% in 2017-2018 (P = .001) compared to baseline, with an absolute reduction of 13% and 12% over those time periods. CONCLUSION: Our data suggests that the adoption of a simple, standardized perioperative and periprocedural CA prevention, diagnosis, and treatment plan can result in sustained reductions in the occurrence of perioperative CAs.

Reasons for discontinuation of acute postoperative pain ketamine infusions: A retrospective case-control study.

PURPOSE: The purpose of the study was to investigate factors associated with early discontinuation of low-dose ketamine infusions due to adverse drug events (ADEs). METHODS: A retrospective, matched case-control study of surgical patients who received low-dose ketamine infusions for postoperative pain over 6 years was conducted. Forty-seven study patients, who required early discontinuation of their infusion due to ADEs, were included and matched 1:1 with 47 controls, who did not experience ADEs, for a total of 94 patients. The two groups were compared based on surgery type, American Society of Anesthesiologists (ASA) classification, administration of specific perioperative anxiolytic, anesthetic, and analgesic medications, and use of regional anesthesia. RESULTS: Of the study patients, 44.7% underwent spine procedures (vs. 34% of controls), 27.6% underwent abdominal procedures (vs. 8.5% of controls), 19.2% underwent orthopedic procedures (vs. 46.8% of controls), and 8.5% underwent thoracic procedures (vs. 6.4% of controls). There were no statistically significant differences in ASA classification, pre-operative gabapentinoid and antidepressant use, average ketamine infusion dose, or postoperative use of peripheral nerve catheters, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, muscle relaxants, and nonbenzodiazepine sleep aides. Study patients had higher rates of intra-operative volatile anesthetic use (78.7% vs. 57.7%, p = 0.03) and more postoperative opioid patient-controlled analgesia (PCA) use (53.2% vs. 29.8%, p = 0.02) than controls. Control patients had higher rates of preoperative opioid use (76.7% vs. 53.2%, p = 0.02) and premedication with midazolam (89.4% vs. 70.2%, p = 0.02) than study patients. CONCLUSION: Patients who required discontinuation of their low-dose ketamine infusion due to ADEs were more likely to be opioid naïve, received less pre-operative benzodiazepines, and had greater postoperative opioid PCA requirements. Control patients, on the other hand, had higher rates of pre-operative opioid use and experienced fewer ADEs despite greater total ketamine doses.

Anemia, sex, and race as predictors of morbidity or mortality after knee arthroplasty surgery.

BACKGROUND: Anemia is associated with poor outcome after major joint replacement surgery, but it is unclear whether sex and race modify its impact on outcome. We hypothesized that anemia would be associated with increased morbidity or mortality after knee arthroplasty surgery and that sex and race would be effect modifiers for this relationship. STUDY DESIGN AND METHODS: We performed a retrospective cohort study of elective knee arthroplasty patients between 2013 and 2018 using data from the National Surgical Quality Improvement Program. Morbidity or mortality after surgery was compared between patients without anemia, with mild anemia, and with moderate to severe anemia. Multivariable logistic regression was used to determine adjusted odds for morbidity or mortality with anemia. Interaction terms were entered into the model to test for effect modification by sex and race. RESULTS: 243 491 patients were included and 30 135 patients (12.4%) were anemic. Morbidity or mortality occurred in 3.7% of patients without anemia, 5.2% of patients with mild anemia, and 7.1% of patients with moderate to severe anemia (P < .001). After adjustment for confounding variables, mild anemia OR = 1.36 (95% CI = 1.28-1.45), and moderate to severe anemia OR = 1.92 (95% CI = 1.72-2.13) were associated with increased odds of morbidity or mortality. Sex, but not race, was a significant effect modifier with men having a greater increase in morbidity or mortality when anemic (P = .02). CONCLUSIONS: Anemia is associated with increased morbidity or mortality after knee arthroplasty surgery and men have a greater increase in perioperative risk than women when anemic.

Paravertebral block for radiologically inserted gastrostomy tube placement in amyotrophic lateral sclerosis.

INTRODUCTION: Radiologically inserted gastrostomy (RIG) placement in patients with amyotrophic lateral sclerosis (ALS) carries risks related to periprocedural sedation and analgesia. To minimize these risks, we used a paravertebral block (PVB) technique for RIG placement. METHODS: We retrospectively reviewed patients with ALS undergoing RIG placement under PVB between 2013 and 2017. RESULTS: Ninety-nine patients with ALS underwent RIG placement under PVB. Median (range) age was 66 (28 to 86) years, ALS Functional Rating Scale-Revised score was 27 (6 to 45), and forced vital capacity was 47% (8%-79%) at time of RIG placement. Eighty-five (85.9%) patients underwent RIG placement as outpatients, with a mean postanesthesia care unit stay of 2.3 hours. The readmission rate was 4% at both 1 and 30 days postprocedure. DISCUSSION: PVB for RIG placement has a low rate of adverse events and provides effective periprocedural analgesia in patients with ALS, the majority of whom can be treated as outpatients.

Sugammadex use in patients with end-stage renal disease: a historical cohort study.

PURPOSE: While sugammadex (SGX) is not approved for use in patients with end-stage renal disease (ESRD), its administration in this patient population has been reported. We designed the current study to review all instances of patients with ESRD receiving SGX and to describe their clinical outcomes. METHODS: This is a historical cohort study of 219 patients with chronic kidney disease stage 5 who received SGX in one of three hospital locations within the same academic health system. Data were collected between 7 March 2016 and 1 August 2019 and included demographics, notable events from the anesthesia records, and postoperative complications. The primary outcome included any complication possibly related to SGX such as hypersensitivity reactions, need for reintubation, hypoxemia, pneumonia, and residual neuromuscular blockade. Secondary outcomes included any other complication not included in the primary outcome and/or patient mortality within 30 days after the procedure. RESULTS: No patient experienced a hypersensitivity reaction. Three patients required reintubation while two patients developed hypoxemia that did not require reintubation. One patient developed hospital-acquired pneumonia. Fifty (23%) patients developed other postoperative complications (different from our primary outcome) and nine patients (4%) died during the subsequent 30 postoperative days. None of the primary or secondary outcomes appeared to be related to SGX use. CONCLUSIONS: We provide incremental evidence that SGX could be considered as an alternative neuromuscular blockade reversal agent in patients with ESRD.

RéSUMé: OBJECTIF : Bien que le sugammadex (SGX) ne compte pas parmi ses indications une utilisation chez les patients atteints d'insuffisance rénale terminale (IRT), son administration à cette population de patients est rapportée. Nous avons conçu cette étude afin de passer en revue tous les cas de patients atteints d'IRT ayant reçu du SGX et décrire leurs devenirs cliniques. MéTHODE : Il s'agit d'une étude de cohorte historique portant sur 219 patients atteints d'insuffisance rénale chronique de stade 5 ayant reçu du SGX dans l'un de trois hôpitaux appartenant au même réseau de santé universitaire. Les données démographiques, les événements significatifs notés dans les dossiers anesthésiques et les complications postopératoires ont été colligés entre le 7 mars 2016 et le 1er août 2019. Le critère d'évaluation principal incluait toute complication possiblement liée à l'utilisation de SGX telle qu'une réaction d'hypersensibilité, une réintubation, une hypoxémie, une pneumonie, et un bloc neuromusculaire résiduel. Les critères d'évaluation secondaires comprenaient toute autre complication non incluse dans notre critère d'évaluation principal et/ou la mortalité des patients dans les 30 jours suivant l'intervention. RéSULTATS : Aucun patient n'a eu de réaction d'hypersensibilité. Trois patients ont dû être réintubés, et deux patients ont développé une hypoxémie qui n'a pas nécessité de réintubation. Un patient a contracté une pneumonie nosocomiale. Cinquante (23 %) patients ont souffert d'autres complications postopératoires (différentes de notre critère d'évaluation principal) et neuf patients (4 %) sont décédés au cours des 30 jours postopératoires subséquents. Aucun de nos critères d'évaluation primaire ou secondaires ne semblaient liés à l'utilisation de SGX. CONCLUSION : Nous proposons des données probantes supplémentaires selon lesquelles le SGX pourrait être envisagé comme agent décurarisant alternatif chez les patients atteints d'IRT.

Tranexamic Acid Administration Is Not Associated With an Increase in Complications in High-Risk Patients Undergoing Primary Total Knee or Total Hip Arthroplasty: A Retrospective Case-Control Study of 38,220 Patients.

BACKGROUND: Tranexamic acid (TXA) administration to reduce postoperative blood loss and transfusion is a well-established practice for total knee arthroplasty (TKA) and total hip arthroplasty (THA). However, clinical concerns remain about the safety of TXA in patients with a history of a prothrombotic condition. We sought to determine the risk of complications between high-risk and low-risk TKA and THA patients receiving TXA. METHODS: We retrospectively reviewed 38,220 patients (8877 high-risk cases) who underwent primary TKA and THA between 2011 and 2017 at our institution. Intravenous TXA was administered in 20,501 (54%) of cases. The rates of thrombotic complications (deep vein thrombosis [DVT], pulmonary embolism [PE], myocardial infarction [MI], and cerebrovascular accident [CVA]) as well as mortality and readmission were assessed at 90 days postoperatively. Additionally, we evaluated 90-day postoperative occurrence of DVT and PE separate from occurrence of MI and CVA. Patients were categorized as high risk if they had a past medical history of a prothrombotic condition prior to surgery. RESULTS: There was no significant difference in the odds of these adverse outcomes between high-risk patients who received TXA and high-risk patients who did not receive TXA (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.85-1.18). There were also no differences when evaluating the odds of 90-day postoperative DVT and PE (OR 0.84, 95% CI 0.59-1.19) nor MI and CVA (OR 0.91, 95% CI 0.56-1.49) for high-risk patients receiving TXA vs high-risk patients who did not receive TXA. CONCLUSION: TXA administration to high-risk TKA and THA patients is not associated with a statistically significant difference in adverse outcomes. We present incremental evidence in support of TXA administration for high-risk patients undergoing primary arthroplasties.

Peripheral Nerve Blocks and Immediate Postoperative Recovery: A Single-Institution Survey of Perianesthesia Nurses' Preferences and Opinions.

PURPOSE: To ascertain the preferences of perianesthesia nurses regarding peripheral nerve blocks (PNBs) and their impact on patient recovery after total joint replacement (TJR). DESIGN: Survey of perianesthesia nurses at a single medical center. METHODS: Fifty-nine perianesthesia nurses completed a 23-question survey on PNBs for TJR. FINDINGS: Most agreed PNBs improved patients' pain after knee, hip, and shoulder TJR (35 [92.1%], 35 [92.1%], and 34 [91.9%], respectively). Most felt lower extremity PNBs increased risk of falling (26 [70.3%]), whereas 7 of 35 (20.0%) felt patients fell more after spinal anesthesia than after general anesthesia. Respondents preferred a block to opioid-based analgesia if they were to have lower extremity TJR or total shoulder replacement (100% [30/30 and 33/33]). CONCLUSIONS: The perianesthesia nurses surveyed felt PNBs improved pain control and patient recovery despite a perceived risk of falling for lower extremity TJR, and they preferred PNB when considering TJR surgery for themselves.

Phosphate sink containing two-component signaling systems as tunable threshold devices.

Synthetic biology aims to design de novo biological systems and reengineer existing ones. These efforts have mostly focused on transcriptional circuits, with reengineering of signaling circuits hampered by limited understanding of their systems dynamics and experimental challenges. Bacterial two-component signaling systems offer a rich diversity of sensory systems that are built around a core phosphotransfer reaction between histidine kinases and their output response regulator proteins, and thus are a good target for reengineering through synthetic biology. Here, we explore the signal-response relationship arising from a specific motif found in two-component signaling. In this motif, a single histidine kinase (HK) phosphotransfers reversibly to two separate output response regulator (RR) proteins. We show that, under the experimentally observed parameters from bacteria and yeast, this motif not only allows rapid signal termination, whereby one of the RRs acts as a phosphate sink towards the other RR (i.e. the output RR), but also implements a sigmoidal signal-response relationship. We identify two mathematical conditions on system parameters that are necessary for sigmoidal signal-response relationships and define key parameters that control threshold levels and sensitivity of the signal-response curve. We confirm these findings experimentally, by in vitro reconstitution of the one HK-two RR motif found in the Sinorhizobium meliloti chemotaxis pathway and measuring the resulting signal-response curve. We find that the level of sigmoidality in this system can be experimentally controlled by the presence of the sink RR, and also through an auxiliary protein that is shown to bind to the HK (yielding Hill coefficients of above 7). These findings show that the one HK-two RR motif allows bacteria and yeast to implement tunable switch-like signal processing and provides an ideal basis for developing threshold devices for synthetic biology applications.