Assessment of Posttransplant Bacteremia Caused by Extended-Spectrum Beta-Lactamase-Producing Gram-Negative Bacteria Among Kidney Transplant Recipients.

BACKGROUND: Extended-spectrum beta-lactamase-producing gram-negative rods (ESBL-GNR) are a rising cause of bacteremia in kidney transplant recipients (KT). The study purpose was to examine patient mortality, allograft survival, estimated glomerular filtration rate (eGFR) at the end of 1 year, and readmission rates while looking at treatment strategies among KTs with ESBL-GNR and non-ESBL-GNR bacteremia at our institution. METHODS: This study was a retrospective, cohort analysis of KTs with gram-negative bacteremia from January 1, 2020, to December 31, 2021. The primary outcome of the study was mortality. Patient outcomes were assessed for 365 days after positive blood cultures. RESULTS: The study included 63 patients. Of these, 18 (29%) patients had bacteremia caused by an ESBL-GNR and 45 (71%) patients had bacteremia caused by a non-ESBL-GNR. Patient survival at 90 days was 94% in the ESBL-GNR group and 96% in the non-ESBL-GNR group. Ciprofloxacin was the most common antimicrobial therapy at discharge (68.9%) in the non-ESBL-GNR group whereas ertapenem was the most common in the ESBL-GNR group (44.5%). Median eGFR at discharge was 41 mL/min/1.73 m2 in the ESBL-GNR group and 48 mL/min/1.73 m2 in the non-ESBL-GNR group. Ninety-day readmission occurred in 9 (50%) ESBL-GNR patients and 14 (32%) non-ESBL-GNR patients. None of the above comparisons are statistically significant (p > 0.05). Eleven (61%) ESBL-GNR and 2 (4%) non-ESBL-GNR patients used outpatient parenteral antimicrobial therapy (p < 0.001). CONCLUSIONS: Among KTs with ESBL-GNR bacteremia, no significant difference was detected in mortality or allograft function compared to non-ESBL-GNR bacteremia.

Transferability of Buckingham Parameters for Short-Range Repulsion between Topological Atoms.

The repulsive part of the Buckingham potential, with parameters A and B, can be used to model deformation energies and steric energies. Both are calculated using the interacting quantum atom energy decomposition scheme where the latter is obtained from the former by a charge-transfer-based energy correction. These energies relate to short-range interactions, specifically the deformation of electron density and steric hindrance, respectively, when topological atoms approach each other. In this work, we calculate and fit the energies of carbonyl carbon, carbonyl oxygen, and, where possible, amine nitrogen atoms to the repulsive part of the Buckingham potential for 26 molecules. We find that while the steric energies of all atom pairs studied display exponential behavior with respect to distance, some deformation energy data do not. The obtained parameters are shown to be transferable by calculating root-mean-square errors of fitted potentials with respect to energy data of the same atom in, as far as possible, all other molecules from our data set. We observed that 36% and 10% of these errors were smaller than 4 kJ mol-1 for steric and deformation energy, respectively. Thus, we find that steric energy parameters are more transferable than deformation energy parameters. Finally, we speculate about the physical meaning of the A and B parameters and the implications of the strong exponential and exponential-linear piecewise relationships that we observe between them.

Who Benefits from Manipulation under Anesthesia Following Total Knee Arthroplasty?

Arthrofibrosis is a multifactorial process that results in decreased knee range of motion (ROM). Manipulation under anesthesia (MUA) is commonly regarded as the preferred initial treatment of arthrofibrosis following total knee arthroplasty (TKA). There have been no well-controlled studies demonstrating that MUA effectively increases ROM in patients who develop arthrofibrosis after TKA when compared with routine care. The purpose of this study was to determine whether MUA had any advantage over routine care in the treatment of patients who developed arthrofibrosis following TKA. The authors identified patients who underwent primary TKA at the authors' institution between 2010 and 2014 and had flexion ≤ 100 degrees at early follow-up. Knees were grouped based on how the arthrofibrosis was treated: those who underwent MUA and those who received routine care. Knee flexion was captured preoperatively (prior to TKA), at early follow-up (prior to MUA or routine care), and at 1-year follow up. Flexion change from early follow-up to 1 year was calculated. The average flexion at 1-year follow-up was not significantly different between the two groups (106.1 ± 11.7 degrees in the routine care group versus 106.3 ± 12.8 degrees in the MUA group). The MUA group had a greater proportion of patients with flexion gains > 20 degrees at final follow-up when compared with patients who underwent routine care (56% vs. 8%, p < 0.0001). This study demonstrates that patients with decreased ROM at early follow-up after primary TKA can expect greater ROM increase at 1-year follow-up if they undergo MUA compared with patients who undergo routine care. (Journal of Surgical Orthopaedic Advances 33(1):033-036, 2024).

Impact of Limiting Vancomycin Loading Doses in Patients With Methicillin-resistant Staphylococcus aureus Infections After Hospital Protocol Revision.

Background: Vancomycin loading doses are commonly used to quickly attain target serum concentrations; however, data supporting their effect on clinical patient outcomes is limited. In April 2020, our institution revised our pharmacist-driven vancomycin dosing protocol to reserve loading doses for hemodynamically unstable patients with suspected serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Prior to the protocol update, all patients treated with vancomycin at our institution received a weight-based loading dose. The purpose of this study is to assess clinical efficacy and safety outcomes related to the use of vancomycin loading doses. Methods: A retrospective, quasi-experimental study was performed to compare clinical outcomes in adult patients treated with vancomycin for laboratory-confirmed MRSA infections. Patients who received vancomycin therapy prior to our institution's vancomycin dosing protocol revisions (pre-intervention) were compared to patients who received vancomycin after the revisions (post-intervention). The primary outcome was all-cause, inpatient mortality. Secondary outcomes included persistent signs and symptoms of infection ≥5 days after vancomycin initiation, switch to alternative anti-MRSA therapy, and nephrotoxicity. Results: A total of 122 patients (63 pre-intervention patients and 59 post-intervention patients) were included. Receipt of a vancomycin loading dose did not impact the rate of inpatient mortality (4.76%vs 6.78%; OR 1.46, 95% CI [0.31, 6.79]). All secondary outcomes were similar between the two groups, including persistent signs and symptoms of infection, switch to alternative anti-MRSA therapy, and nephrotoxicity. Conclusions: Routine use of vancomycin loading doses is not associated with improved outcomes in hemodynamically stable patients with MRSA infections.

Construction of a Gaussian Process Regression Model of Formamide for Use in Molecular Simulations.

FFLUX, a novel force field based on quantum chemical topology, can perform molecular dynamics simulations with flexible multipole moments that change with geometry. This is enabled by Gaussian process regression machine learning models, which accurately predict atomic energies and multipole moments up to the hexadecapole. We have constructed a model of the formamide monomer at the B3LYP/aug-cc-pVTZ level of theory capable of sub-kJ mol-1 accuracy, with the maximum prediction error for the molecule being 0.8 kJ mol-1. This model was used in FFLUX simulations along with Lennard-Jones parameters to successfully optimize the geometry of formamide dimers with errors smaller than 0.1 Šcompared to those obtained with D3-corrected B3LYP/aug-cc-pVTZ. Comparisons were also made to a force field constructed with static multipole moments and Lennard-Jones parameters. FFLUX recovers the expected energy ranking of dimers compared to the literature, and changes in C═O and C-N bond lengths associated with hydrogen bonding were found to be consistent with density functional theory.

Lower Extremity Total Joint Arthroplasty Has Minimal Effect on Golf Handicap.

Although the vast majority of arthroplasty surgeons allow patients to return to participation in golf following total knee arthroplasty (TKA) and total hip arthroplasty (THA), there is relatively little published data regarding how TKA or THA affects a patient's golfing ability. The purpose of this study was to determine how golfers' handicaps change following TKA and THA. We mailed a questionnaire to patients who had underwent primary TKA or THA at our institution and asked whether they played golf and for their golf handicap information network (GHIN) number. We then obtained handicap data for each patient that provided a GHIN number. Handicap increased 0.9 strokes 1 year following THA; however, this difference was not statistically significant (p = 0.20). Handicap increased 0.3 strokes 1 year following TKA; however, this difference was not statistically significant (p = 0.29). Our study demonstrates that despite improved implants, surgical techniques, and rehabilitation protocols that golf handicap does not change significantly following lower extremity total joint arthroplasty (TJA). (Journal of Surgical Orthopaedic Advances 29(4):216-218, 2020).

Gait and Functional Outcomes Between Cruciate-Retaining and Cruciate-Substituting Implants in Total Knee Arthroplasty: A Prospective, Randomized Study.

Significant debate persists about posterior cruciate-retaining (CR) versus posterior cruciate-substituting (PS) implant design for total knee arthroplasty (TKA). This study sought to test the hypothesis that CR TKA will facilitate improved early functional outcomes in gait compared with PS TKA. Patients were randomized to either the CR or PS implant. Various patient-reported and surgeon-reported outcomes as well as gait analyses were obtained pre- and postoperatively. Patients undergoing PS TKA had higher University of California, Los Angeles activity scores at 12 months. No significant difference in spatiotemporal, kinematic, or kinetic parameters between groups was detected, but there was a trend toward quadriceps overuse gait pattern in the CR group. Patients undergoing TKA with a PS implant were more willing to engage in regular higher level physical activity. The CR implant may be a risk factor for quadriceps overuse gait pattern, while the PS implant may be protective against quadriceps overuse. (Journal of Surgical Orthopaedic Advances 28(3):215-223, 2019).

A Bundle Protocol to Reduce the Incidence of Periprosthetic Joint Infections After Total Joint Arthroplasty: A Single-Center Experience.

BACKGROUND: Periprosthetic joint infection (PJI) represents a devastating complication of total hip arthroplasty (THA) or total knee arthroplasty (TKA). Modifiable patient risk factors as well as various intraoperative and postoperative variables have been associated with risk of PJI. In 2011, our institution formulated a "bundle" to optimize patient outcomes after THA and TKA. The purpose of this report is to describe the "bundle" protocol we implemented for primary THA and TKA patients and to analyze its impact on rates of PJI and readmission. METHODS: Our bundle protocol for primary THA and TKA patients is conceptually organized about 3 chronological periods of patient care: preoperative, intraoperative, and postoperative. The institutional total joint database and electronic medical record were reviewed to identify all primary THAs and TKAs performed in the 2 years before and following implementation of the bundle. Rates of PJI and readmission were then calculated. RESULTS: Thirteen of 908 (1.43%) TKAs performed before the bundle became infected compared to only 1 of 890 (0.11%) TKAs performed after bundle implementation (P = .0016). Ten of 641 (1.56%) THAs performed before the bundle became infected, which was not statistically different from the 4 of 675 (0.59%) THAs performed after the bundle that became infected (P = .09). CONCLUSION: The bundle protocol we describe significantly reduced PJIs at our institution, which we attribute to patient selection, optimization of modifiable risk factors, and our perioperative protocol. We believe the bundle concept represents a systematic way to improve patient outcomes and increase value in total joint arthroplasty.

Patient Factors and Cost Associated with 90-Day Readmission Following Total Hip Arthroplasty.

This study sought to identify specific costs for 90-day readmissions following total hip arthroplasty in a bundled payment system. Hospital billing records revealed 139 readmissions (8.93%) in 1781 patients. Mean costs for surgical readmissions were greater (P=0.002) compared with medical reasons, but similar for Medicare/Medicaid and private payers (P=0.975). Costs for imaging, laboratory workup, medication and transfusions, and hospital cost correlated with increasing SOI (P<0.05). Patients transferred from outside hospitals or rehabilitation had higher hospital (P=0.006) and operating room costs (P=0.001) compared to patients admitted from ED or clinic. Hospitals that care for complex patients with Medicare/Medicaid may experience increased costs for unplanned 90-day readmissions highlighting considerations for payer mix.

Decreased Range of Motion After Total Knee Arthroplasty Is Predicted by the Tampa Scale of Kinesiophobia.

BACKGROUND: Range of motion (ROM) is important for functional outcome after total knee arthroplasty (TKA); however, some patients hesitate to maximize their ROM postoperatively. The Tampa Scale of Kinesiophobia (TSK) measures patients' fear of movement. The primary purpose of this investigation was to determine whether TSK scores correlated with decreased ROM after primary TKA. A secondary purpose was to determine whether biofeedback could increase ROM after TKA. METHODS: Patients were recruited from the senior author's practice between June 2011 and March 2013. A clinical photograph was taken of each patient's knee in maximum passive flexion in the operating room immediately following closure. Patients were randomized to the control or photograph group before incision. A linear mixed model was implemented to determine whether the TSK score and viewing the photo correlated to ROM. RESULTS: Seventy-nine patients were analyzed for correlation between the TSK score and the knee ROM. Sixty patients were analyzed for correlation between viewing the clinical photograph and the knee ROM. The linear mixed model demonstrated a significant negative correlation between the TSK score and both active (ß = -0.47, P < .01) and passive (ß = -0.66, P < .001) knee flexions. There was a trend toward decreased knee flexion among patients shown their clinical photograph. CONCLUSION: The TSK was developed as a tool to identify patients at risk for maladaptive responses to painful stimuli. Our data suggest that the TSK may help arthroplasty surgeons identify patients at risk for decreased ROM after TKA. Showing patients a clinical photograph failed to increase ROM after TKA.

Factors Associated with Range of Motion Recovery Following Manipulation Under Anesthesia.

INTRODUCTION: Stiffness and loss of motion following total knee arthroplasty (TKA) is a complex and multifactorial complication that may require manipulation under anesthesia (MUA). However, patient and surgical factors that potentially influence the development of knee stiffness following TKA are not fully understood. The purpose of this study was to identify patient and surgical factors that may influence range of motion loss following TKA by assessing a cohort of patients that underwent MUA and comparing them to a matched cohort of patients without complications. MATERIALS AND METHODS: The joints registry was searched for patients who underwent MUA following primary TKA between 2004 and 2013. Demographic and surgical information was obtained from the electronic medical record including range of motion (ROM), comorbidities and timing of MUA. Patients who underwent MUA were then double-matched by baseline (prior to primary TKA) knee ROM to patients who underwent primary TKA with normal postoperative range of motion recovery during the same time period. RESULTS: Fifty-two patients (fifty-six knees) (66% female, mean BMI 32.4 kg/m2) underwent MUA after TKA during the study period. MUA was performed a mean of 13.6 weeks after primary TKA. Study patients were double-matched by baseline flexion (mean 107º±2º) to 111 patients (112 knees) with a similar mean baseline flexion (104º±2º, p=0.138). Patients requiring MUA were younger (mean age 56 vs. 64 years, p<0.001), had more comorbidities (5 vs. 3, p<0.001), and a higher number of previous knee surgeries (56% vs. 21%, p<0.001) compared with controls. The risk for requiring MUA following primary TKA was significantly higher (2.4, p<0.001) in patients with previous knee surgery (arthroscopy for meniscal pathology, ACL reconstruction, osteotomies). Tourniquet time, length of stay, number of physical therapy sessions, blood loss >50 mL, and any complication during the hospital stay were not found to be associated with an increased risk of requiring MUA. CONCLUSION: Younger patients with more comorbidities and a history of previous knee surgery were found to have significantly higher risk for developing stiffness and loss of motion requiring MUA after primary TKA in the current study. Patients with this risk profile need to be counseled regarding the risk for postoperative knee stiffness and range of motion loss possibly requiring MUA after primary TKA.

Design and synthesis of a novel series of [1-(4-hydroxy-benzyl)-1H-indol-5-yloxy]-acetic acid compounds as potent, selective, thyroid hormone receptor ß agonists.

The design, synthesis, and structure activity relationships for a novel series of indoles as potent, selective, thyroid hormone receptor ß (TRß) agonists is described. Compounds with >50× binding selectivity for TRß over TRα were generated and evaluation of compound 1c from this series in a model of dyslipidemia demonstrated positive effects on plasma lipid endpoints in vivo.

Effects of patellofemoral overstuffing on knee flexion and patellar kinematics following total knee arthroplasty: a cadaveric study.

PURPOSE: The purpose of this study was to test the hypothesis that overstuffing the patellofemoral joint during total knee arthroplasty (TKA) would decrease passive knee flexion and alter patellar kinematics during knee flexion. METHODS: Ten cadaveric knees were implanted with cruciate-retaining TKAs, and the patellofemoral joint was overstuffed in 2-mm increments with custom-augmented patellar prostheses (+2 mm through +8 mm). Changes to knee flexion, patellar shift, tilt and rotation were measured with an imageless optical-tracking computer navigation system. RESULTS: Knee flexion decreased an average 1.2° with each additional 2 mm of patellar thickness. Compared with control TKA (+0 mm), no significant decrease in knee flexion was detected until the patellofemoral joint was overstuffed with the +8-mm patellar prosthesis. Kinematic tracking data showed significantly greater lateral shift of patella with the +6- and +8-mm prostheses and significantly greater lateral tilt with the +8-mm prosthesis. Overstuffing had no appreciable effect on patellar rotation. CONCLUSIONS: Passive knee flexion after TKA is significantly reduced when overstuffing the patellofemoral joint by +8 mm, and patellofemoral kinematics are altered when overstuffing the joint by +6 mm. These results demonstrate the relatively modest effects of patellofemoral overstuffing on knee flexion and patellar tracking kinematics after TKA.

Imageless computer-assisted versus conventional total hip arthroplasty: one surgeon's initial experience.

Computer-assisted surgery (CAS) systems are advocated to improve component positioning in THA, though potential operative risks and costs of CAS have fueled debate. The present study examines the radiographic outcomes, operative efficiency, cost, and midterm functional outcomes for patients who underwent THA, either with CAS or conventional instrumentation. Patient baseline characteristics were recorded for 126 lower-extremities in the CAS series, and 215 in the conventional series. There was no difference in Harris Hip Score or leg length discrepancy between series. Inclination angle, blood loss, and operating room times were increased for CAS. These results suggest that CAS confers no advantage over conventional methods regarding accuracy of THA component placement, drives unreimbursed increases in procedure costs, may expose patients to additional operative risk, and produces no functional benefit at midterm follow-up.

Incorporating Noncovalent Interactions in Transfer Learning Gaussian Process Regression Models for Molecular Simulations.

FFLUX is a quantum chemical topology-based multipolar force field that uses Gaussian process regression machine learning models to predict atomic energies and multipole moments on the fly for fast and accurate molecular dynamics simulations. These models have previously been trained on monomers, meaning that many-body effects, for example, intermolecular charge transfer, are missed in simulations. Moreover, dispersion and repulsion have been modeled using Lennard-Jones potentials, necessitating careful parametrization. In this work, we take an important step toward addressing these shortcomings and show that models trained on clusters, in this case, a dimer, can be used in FFLUX simulations by preparing and benchmarking a formamide dimer model. To mitigate the computational costs associated with training higher-dimensional models, we rely on the transfer of hyperparameters from a smaller source model to a larger target model, enabling an order of magnitude faster training than with a direct learning approach. The dimer model allows for simulations that account for two-body effects, including intermolecular polarization and charge penetration, and that do not require nonbonded potentials. We show that addressing these limitations allows for simulations that are closer to quantum mechanics than previously possible with the monomeric models.

Acute Kidney Injury After Total Hip and Knee Arthroplasty. What Is the Culprit?

Background: Acute kidney injury (AKI) is associated with increased complications after total hip arthroplasty (THA) and total knee arthroplasty (TKA). The purpose of this study was to determine the risk factors for AKI after THA and TKA and evaluate if preoperative use of antihypertensive drugs is a risk factor for AKI. Methods: A retrospective review of 7406 primary TKAs and THAs (4532 hips and 2874 knees) from 2013 to 2019 was performed. The following preoperative variables were obtained from medical records: medications, chemistry 7 panel, Elixhauser comorbidities, and demographic factors. AKI was defined as an increase in serum creatinine by 26.4 µmol·L-1. Multivariate analysis was performed to identify the risk factors. Results: The overall incidence of postoperative AKI was 6.2% (n = 459). Risk factors for postoperative AKI were found to be: chronic kidney disease (odds ratio [OR] = 7.09; 95% confidence interval [CI]: 4.8-9.4), diabetes (OR: 5.03; 95% CI: 2.8-6.06), ≥3 antihypertensive drugs (OR: 4.2; 95% CI: 2.1-6.2), preoperative use of an angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (OR: 3.8; 95% CI: 2.2-5.9), perioperative vancomycin (OR: 2.7; 95% CI: 1.8-4.6), and body mass index >40 kg/m2 (OR: 1.9; 95% CI: 1.3-3.06). Conclusions: We have identified several modifiable risk factors for AKI that can be optimized prior to an elective THA or TKA. The use of certain antihypertensive agents namely angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and multidrug antihypertensive regimens were found to significantly increase the risk of AKI. Therefore, perioperative management of patients undergoing joint replacement should include medical comanagement with a focus on careful management of antihypertensives.

Model-Informed Precision Dosing Improves Outcomes in Patients Receiving Vancomycin for Gram-Positive Infections.

Background: Consensus guidelines for dosing and monitoring of vancomycin recommend collection of 2 serum concentrations to estimate an area under the curve/minimum inhibitory concentration ratio (AUC/MIC). Use of Bayesian software for AUC estimation and model-informed precision dosing (MIPD) enables pre-steady state therapeutic drug monitoring using a single serum concentration; however, data supporting this approach are limited. Methods: Adult patients with culture-proven gram-positive infections treated with vancomycin ≥72 hours receiving either trough-guided or AUC-guided therapy were included in this retrospective study. AUC-guided therapy was provided using MIPD and single-concentration monitoring. Treatment success, vancomycin-associated acute kidney injury (VA-AKI), and inpatient mortality were compared using a desirability of outcome ranking analysis. The most desirable outcome was survival with treatment success and no VA-AKI, and the least desirable outcome was death. Results: The study population (N = 300) was comprised of an equal number of patients receiving AUC-guided or trough-guided therapy. More patients experienced the most desirable outcome in the AUC-guided group compared to the trough-guided group (58.7% vs 46.7%, P = .037). Rates of VA-AKI were lower (21.3% vs 32.0%, P = .037) and median hospital length of stay was shorter (10 days [interquartile range {IQR}, 8-20] vs 12 days [IQR, 8-25]; P = .025) among patients receiving AUC-guided therapy. Conclusions: AUC-guided vancomycin therapy using MIPD and single-concentration monitoring improved outcomes in patients with culture-proven gram-positive infections. Safety was improved with reduced incidence of VA-AKI, and no concerns for reduced efficacy were observed. Moreover, MIPD allowed for earlier assessment of AUC target attainment and greater flexibility in the collection of serum vancomycin concentrations.

Socio-demographic and comorbid risk factors for poor prognosis in patients hospitalized with community-acquired bacterial pneumonia in southeastern US.

BACKGROUND: How socio-demographic characteristics and comorbidities affect bacterial community-acquired pneumonia (CAP) prognosis during/after hospitalization is important in disease management. OBJECTIVES: To identify predictors of medical intensive care unit (MICU) admission, length of hospital stay (LOS), in-hospital mortality, and bacterial CAP readmission in patients hospitalized with bacterial CAP. METHODS: ICD-9/10 codes were used to query electronic medical records to identify a cohort of patients hospitalized for bacterial CAP at a tertiary hospital in Southeastern US between 01/01/2013-12/31/2019. Adjusted accelerated failure time and modified Poisson regression models were used to examine predictors of MICU admission, LOS, in-hospital mortality, and 1-year readmission. RESULTS: There were 1956 adults hospitalized with bacterial CAP. Median (interquartile range) LOS was 11 days (6-23), and there were 26 % (513) MICU admission, 14 % (266) in-hospital mortality, and 6 % (117) 1-year readmission with recurrent CAP. MICU admission was associated with heart failure (RR 1.38; 95 % CI 1.17-1.62) and obesity (RR 1.26; 95 % CI 1.04-1.52). Longer LOS was associated with heart failure (adjusted time ratio[TR] 1.27;95 %CI 1.12-1.43), stroke (TR 1.90;95 %CI 1.54,2.35), type 2 diabetes (TR 1.20;95 %CI 1.07-1.36), obesity (TR 1.50;95 %CI 1.31-1.72), Black race (TR 1.17;95 %CI 1.04-1.31), and males (TR 1.24;95 %CI 1.10-1.39). In-hospital mortality was associated with stroke (RR 1.45;95 %CI 1.03-2.04) and age ≥65 years (RR 1.34;95 %CI 1.06-1.68). 1-year readmission was associated with COPD (RR 1.55;95 %CI 1.05-2.27) and underweight BMI (RR 1.74;95 %CI 1.04-2.90). CONCLUSIONS: Comorbidities and socio-demographic characteristics have varying impacts on bacterial CAP in-hospital prognosis and readmission. More studies are warranted to confirm these findings to develop comprehensive care plans and inform public health interventions.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2022.

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor identified antimicrobial stewardship-related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation.

Profluorogenic reductase substrate for rapid, selective, and sensitive visualization and detection of human cancer cells that overexpress NQO1.

Achieving the vision of identifying and quantifying cancer-related events and targets for future personalized oncology is predicated on the existence of synthetically accessible and economically viable probe molecules fully able to report the presence of these events and targets in a rapid and highly selective and sensitive fashion. Delineated here are the design and evaluation of a newly synthesized turn-on probe whose intense fluorescent reporter signature is revealed only through probe activation by a specific intracellular enzyme present in tumor cells of multiple origins. Quenching of molecular probe fluorescence is achieved through unique photoinduced electron transfer between the naphthalimide dye reporter and a covalently attached, quinone-based enzyme substrate. Fluorescence of the reporter dye is turned on by rapid removal of the quinone quencher, an event that immediately occurs only after highly selective, two-electron reduction of the sterically and conformationally restricted quinone substrate by the cancer-associated human NAD(P)H:quinone oxidoreductase isozyme 1 (hNQO1). Successes of the approach include rapid differentiation of NQO1-expressing and -nonexpressing cancer cell lines via the unaided eye, flow cytometry, fluorescence imaging, and two-photon microscopy. The potential for use of the turn-on probe in longer-term cellular studies is indicated by its lack of influence on cell viability and its in vitro stability.