Ru(II) Oligothienyl Complexes with Fluorinated Ligands: Photophysical, Electrochemical, and Photobiological Properties.

A series of Ru(II) complexes incorporating two 4,4'-bis(trifluoromethyl)-2,2'-bipyridine (4,4'-btfmb) coligands and thienyl-appended imidazo[4,5-f][1,10]phenanthroline (IP-nT) ligands was characterized and assessed for phototherapy effects toward cancer cells. The [Ru(4,4'-btfmb)2(IP-nT)]2+ scaffold has greater overall redox activity compared to Ru(II) polypyridyl complexes such as [Ru(bpy)3]2+. Ru-1T-Ru-4T have additional oxidations due to the nT group and additional reductions due to the 4,4'-btfmb ligands. Ru-2T-Ru-4T also exhibit nT-based reductions. Ru-4T exhibits two oxidations and eight reductions within the potential window of -3 to +1.5 V. The lowest-lying triplets (T1) for Ru-0T-2T are metal-to-ligand charge-transfer (3MLCT) excited states with lifetimes around 1 µs, whereas T1 for Ru-3T-4T is longer-lived (∼20-24 µs) and of significant intraligand charge-transfer (3ILCT) character. Phototoxicity toward melanoma cells (SK-MEL-28) increases with n, with Ru-4T having a visible EC50 value as low as 9 nM and PI as large as 12,000. Ru-3T and Ru-4T retain some of this activity in hypoxia, where Ru-4T has a visible EC50 as low as 35 nM and PI as high as 2900. Activity over six biological replicates is consistent and within an order of magnitude. These results demonstrate the importance of lowest-lying 3ILCT states for phototoxicity and maintaining activity in hypoxia.

Lipoprotein(a): Emerging insights and therapeutics.

The strong association between lipoprotein (a) [Lp(a)] and atherosclerotic cardiovascular disease has led to considerations of Lp(a) being a potential target for mitigating residual cardiovascular risk. While approximately 20 % of the population has an Lp(a) level greater than 50 mg/dL, there are no currently available pharmacological lipid-lowering therapies that have demonstrated substantial reduction in Lp(a). Novel therapies to lower Lp(a) include antisense oligonucleotides and small-interfering ribonucleic acid molecules and have shown promising results in phase 2 trials. Phase 3 trials are currently underway and will test the causal relationship between Lp(a) and ASCVD and whether lowering Lp(a) reduces cardiovascular outcomes. In this review, we summarize emerging insights related to Lp(a)'s role as a risk-enhancing factor for ASCVD, association with calcific aortic stenosis, effects of existing therapies on Lp(a) levels, and variations amongst patient populations. The evolving therapeutic landscape of emerging therapeutics is further discussed.

Rectovaginal Fistulas Not Involving the Rectovaginal Septum Should Be Treated Like Anal Fistulas: A New Concept and Proposal for a Reclassification of Rectovaginal Fistulas.

Background: Many rectovaginal fistulas(RVF), especially low RVF, do not involve/penetrate the RV-septum, but due to lack of proper nomenclature, such fistulas are also managed like RVF (undertaking repair of RV-septum) and inadvertently lead to the formation of a high RVF (involving RV-septum) in many cases. Therefore, REctovaginal Fistulas, Not Involving the Rectovaginal Septum, should be Treated like Anal fistulas(RENISTA) to prevent any risk of injury to the RV septum. This concept(RENISTA) was tested in this study. Methods: RVFs not involving RV-septum were managed like anal fistulas, and the RV-septum was not cut/incised. MRI, objective incontinence scoring, and anal manometry were done preoperatively and postoperatively. High RVF (involving RV-septum) were excluded. Results: Twenty-seven patients with low RVF (not involving RV-septum) were operated like anal fistula[age:35.2±9.2 years, median follow-up-15 months (3-36 months)]. 19/27 were low fistula[<1/3 external anal sphincter(EAS) involved] and fistulotomy was performed, whereas 8/27 were high fistula (>1/3 EAS involved) and underwent a sphincter-sparing procedure. Three patients were excluded. The fistula healed well in 22/24 (91.7%) patients and did not heal in 2/24 (8.3%). The healing was confirmed on MRI, and there was no significant change in mean incontinence scores and anal pressures on tonometry. RV-septum injury did not occur in any patient. Conclusions: RVF not involving RV-septum were managed like anal fistulas with a high cure rate and no significant change in continence. RV-septum injury or formation of RVF with septum involvement did not occur in any patient. The RENISTA concept was validated in the present study. A new classification was developed to prevent any inadvertent injury to the RV-septum.

Socioeconomic Disparities in Women's Cardiovascular Health in the United States and Canada.

Cardiovascular disease has been the leading cause of death in the United States and Canada for decades. Although it affects millions of people across a multitude of backgrounds, notable disparities in cardiovascular health are observed among women and become more apparent when accounting for race and socioeconomic status. Although intrinsic sex-specific physiologic differences predispose women to poorer outcomes, social determinants of health (SDOH) and biases at both the individual provider and the larger health care system levels play an equal, if not greater, role. This review examines socioeconomic disparities in women compared with men regarding cardiovascular risk factors, treatments, and outcomes. Although various at-risk subpopulations exist, we highlight the impact of SDOH in specific populations, including patients with disabilities, transgender persons, and South Asian and Indigenous populations. These groups are underrepresented in studies and experience poorer health outcomes owing to structural barriers to care. These findings emphasise the significance of understanding the interplay of different socioeconomic factors and how their stacking can negatively affect women's cardiovascular health. To address these disparities, we propose a multipronged approach to augment culturally sensitive and patient-centred care. This includes increased cardiovascular workforce diversity, inclusion of underrepresented populations into analyses of cardiovascular metrics, and greater utilisation of technology and telemedicine to improve access to health care. Achieving this goal will necessitate active participation from patients, health care administrators, physicians, and policy makers, and is imperative in closing the cardiovascular health gap for women over the coming decades.

Atherosclerotic coronary plaque regression from lipid-lowering therapies: A meta-analysis and meta-regression.

Background: Studies reporting collective and comprehensive data on plaque regression of different lipid-lowering therapies (LLTs) are limited. Objectives: We evaluated plaque regression of LLTs based on multiple markers and performed subgroup analyses based on LLT type and post-treatment LDL-C levels. Methods: A literature search was performed to identify studies assessing plaque regression from LLTs. The following LLTs groups were included: High-intensity statin (HIS), HIS+ eicosapentaenoic acid (EPA), HIS + ezetimibe, Low-intensity statin (LIS), LIS + EPA, LIS + Ezetimibe, and PCSK9 inhibitors. Our primary outcomes were change in percent atheroma volume (PAV). Secondary outcomes included mean differences in total atheroma volume (TAV), lumen, plaque, and vessel volumes, fibrous cap thickness (FCT), and lipid arc (LA). Subgroup analyses were performed on LLT type and post-treatment LDL-C levels. Meta-regression was performed to control for covariates. Results: We identified 51 studies with 9,113 adults (22 % females). LLTs reduced PAV levels (-1.10 % [-1.63, -0.56], p < 0.01), with significant reduction observed with HIS, LIS + ezetimibe, LIS + EPA, and PCSK9 inhibitors. LLTs reduced TAV levels (-5.84 mm3 [-8.64 to -3.04] p < 0.01), mainly driven by HIS (-7.60 mm3 [-11.89, -3.31] p < 0.01). LLTs reduced plaque volume and LA and increased FCT. Conclusion: The plaque regression associated with LLTs is observed to be mainly driven by HIS, reducing both TAV and PAV. This suggest that HIS is the most effective LLT for plaque regression. Unstructured abstract: We evaluated plaque regression of LLTs from 51 studies. We found that while reduction of PAV (-1.10 % [-1.63, -0.56], p < 0.01) were present across different LLT types, reduction of TAV (-5.84 mm3 [-8.64 to -3.04] p < 0.01) was mainly driven by HIS (-7.60 mm3 [-11.89, -3.31] p < 0.01). These results suggest that HIS is the most effective LLT for plaque regression.

Clinical Evaluation of Diode Laser as an Adjunct to Scaling and Root Planing in Patients With Chronic Periodontitis and Type II Diabetes Mellitus: A Split-Mouth Study.

INTRODUCTION:  The primary goal of periodontal therapy is to arrest the inflammatory disease process which is done by non-surgical and surgical therapies in order to reduce the microorganisms. The outcome of periodontal therapy may not reveal the desired results owing to inaccessible areas for instrumentation, pathogenicity, resistance of the microorganisms, or even due to compromised host response to the treatment. Thus, adjunctive laser therapy has been proposed as a novel treatment modality in the treatment of periodontal disease.  Aim: The aim of this study was to clinically evaluate the effect of a 980 nm diode laser (DEN10B; Wuhan Gigaa Optronics Technology Co., Ltd., Wuhan, China) therapy as an adjunct to scaling and root planing in patients with chronic periodontitis and type II diabetes. METHODS: Twenty patients were divided into two groups in a split-mouth study design. Group I (Control) comprised mechanical debridement alone and Group II (test) comprised mechanical debridement followed by adjunctive laser therapy. The clinical parameters were recorded at baseline, six weeks, and three months, and the results were analyzed. RESULTS: There was a significant improvement in gingival and plaque index in the test group. Though there was no significant improvement in probing pocket depth and clinical attachment, the results in the test group were superior relative to the control group. CONCLUSION: Non-surgical periodontal therapy with adjunctive use of diode laser is effective in the management of generalized chronic periodontitis in patients with type II diabetes which led to a significant reduction in plaque score, gingival index score, probing pocket depth, and gain in clinical attachment level.

Efficacy and Safety of Tirzepatide in Overweight and Obese Adult Patients with Type 1 Diabetes.

Introduction and Objective: Most patients with type 1 diabetes (T1D) in the United States are overweight (OW) or obese (OB), contributing to insulin resistance and suboptimal glucose control. The primary Food and Drug Administration-approved treatment for T1D is insulin, which may adversely affect weight. Tirzepatide is approved for managing type 2 diabetes, improves glucose control, facilitates weight loss, and improves cardiovascular disease outcomes. We assessed the use of tirzepatide in OW/OB subjects with T1D. Methods: This was a retrospective single-center real-world study in 62 OW/OB adult patients with T1D who were prescribed tirzepatide (treated group) and followed for 1 year. At least 3 months of use of tirzepatide was one of the inclusion criteria. Based on the inclusion criteria, this study represents 62 patients out of 184 prescribed tirzepatide. The control group included 37 OW/OB patients with T1D (computer frequency matched by age, duration of diabetes, gender, body mass index (BMI), and glucose control) who were not using any other weight-loss medications during the same period. The mean (±standard deviation [SD]) dose of weekly tirzepatide at 3 months was 5.6 ± 1.9 mg that increased to 9.7 ± 3.3 mg at 1 year. Results: The gender, mean baseline age, duration of diabetes, and glycosylated hemoglobin (HbA1c) were similar in the two groups, whereas BMI and weight were higher in the treated group. There were significantly larger declines in BMI and weight in the treated group than in controls across all time points among those in whom data were available. HbA1c decreased in the treated group as early as 3 months and was sustained through a 1-year follow-up (-0.67% at 1 year). As expected, insulin dose decreased at 3 months and throughout the study period. There were no reported hospitalizations from severe hypoglycemia or diabetic ketoacidosis. The mean glucose, time-in-range, time-above-range, SD, and coefficient of variation (continuous glucose monitoring metrics) significantly improved in the treated group. Conclusions: In this pilot (off label) study, we conclude that tirzepatide facilitated an average 18.5% weight loss (>46 pounds) and improved glucose control in OW/OB patients with T1D at 1 year. For safe use of tirzepatide in patients with T1D, we strongly recommend a large prospective randomized control trial in OW/OB patients with T1D.

Efficacy of Semaglutide in Overweight and Obese Patients with Type 1 Diabetes.

Introduction: More than two-thirds of patients with type 1 diabetes (T1D) are overweight (OW) and/or obese (OB) in the USA and Western Europe, resulting in insulin resistance as in type 2 diabetes. None of the currently available glucagon like polypeptide 1 (GLP-1) analogs are approved for patients with T1D. A higher dose of semaglutide has been approved by the Food and Drug Administration (FDA) for subjects with body mass index (BMI) >27 kg/m2. We evaluated the real-world use of semaglutide in patients with T1D. Methods: This was a retrospective chart review study of 50 OW or OB patients with T1D who were initiated on semaglutide and followed for 1 year. The control group comprised of 50 computer-matched patients (for sex, race, weight, BMI, and diabetes duration) during a similar time period and were not on any weight loss medications. Results: Most patients (92%) were non-Hispanic white in both arms. Mean ± standard deviation (SD) age and duration of diabetes were 42 ± 11 and 27 ± 12 years, respectively. The continuous glucose monitors (CGM), insulin pump use, baseline BMI and body weight were also similar in the two groups. Baseline glycosylated hemoglobin (HbA1c) was insignificantly lower in the semaglutide group (7.6% vs. 8.2%, respectively; P = non-significant [NS]). Total daily insulin dose (TDD) and insulin dose per kg body weight were higher in the semaglutide group at baseline with no difference in basal or prandial insulin dose. There were significantly greater declines in mean (±SD), BMI (7.9% ± 2.6%), body weight (15.9 lbs ± 5.4 lbs), HbA1c, CGM glucose SD and coefficient of variation (CV), and increase in CGM time in range (TIR) in the semaglutide group compared to the control group with no difference in insulin dose changes, time above range (TAR), or time below range (TBR). Conclusions: We conclude that use of semaglutide in patients who are OW and/or OB with T1D was effective in lowering body weight and BMI, and improving glycemic metrics in this pilot real-world study. We strongly recommend performing prospective, large-randomized clinical trials with newer GLP-1 analogs like semaglutide and tirzepatide (twin-cretin) for subjects with T1D associated with OW and/or OB.

Multi-locus sequence typing of geographically and temporally diverse strains of Mycoplasma hominis.

This study aimed to investigate the genetic diversity of 108 geographically and temporally diverse strains of Mycoplasma hominis using a multi-locus sequence typing scheme (MLST). We extracted MLST data of 87 strains from PubMLST database and retrieved MLST gene sequences from 21 complete genomes of M. hominis available in GenBank database. MLST scheme identified 65 Sequence types (STs), which were grouped into five clonal complexes (CC) and 47 singletons. Phylogenetic analysis revealed that the majority of M. hominis isolates were clustered according to their country of origin, showing some significant specificity trends for the nation. Although recombination was detected, it was not significant enough to alter the clonal population structure of M. hominis. In sum, MLST scheme provides insightful data on the phylogenetics of international strains of M. hominis, arguing for the existence of genetically differentiable STs according to their origin of isolation.

Lipoprotein(a) and Major Adverse Cardiovascular Events in Patients With or Without Baseline Atherosclerotic Cardiovascular Disease.

BACKGROUND: Lipoprotein(a) [Lp(a)] is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). However, whether the optimal Lp(a) threshold for risk assessment should differ based on baseline ASCVD status is unknown. OBJECTIVES: The purpose of this study was to assess the association between Lp(a) and major adverse cardiovascular events (MACE) among patients with and without baseline ASCVD. METHODS: We studied a retrospective cohort of patients with Lp(a) measured at 2 medical centers in Boston, Massachusetts, from 2000 to 2019. To assess the association of Lp(a) with incident MACE (nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularization, or cardiovascular mortality), Lp(a) percentile groups were generated with the reference group set at the first to 50th Lp(a) percentiles. Cox proportional hazards modeling was used to assess the association of Lp(a) percentile group with MACE. RESULTS: Overall, 16,419 individuals were analyzed with a median follow-up of 11.9 years. Among the 10,181 (62%) patients with baseline ASCVD, individuals in the 71st to 90th percentile group had a 21% increased hazard of MACE (adjusted HR: 1.21; P < 0.001), which was similar to that of individuals in the 91st to 100th group (adjusted HR: 1.26; P < 0.001). Among the 6,238 individuals without established ASCVD, there was a continuously higher hazard of MACE with increasing Lp(a), and individuals in the 91st to 100th Lp(a) percentile group had the highest relative risk with an adjusted HR of 1.93 (P < 0.001). CONCLUSIONS: In a large, contemporary U.S. cohort, elevated Lp(a) is independently associated with long-term MACE among individuals with and without baseline ASCVD. Our results suggest that the threshold for risk assessment may be different in primary vs secondary prevention cohorts.

Dysphagia in a Patient With Lewy Body Dementia and Incidental Anterior Cervical Osteophyte: A Case Report.

One of the common problems affecting the elderly is dysphagia, which can be brought on by several things, including the presence of anterior cervical osteophytes. In this case study, a patient with Lewy body dementia is shown to have a case of dysphagia. The patient's primary complaint was dysphagia, which prompted questions regarding the development of underlying Lewy body dementia combined with gradual cognitive deterioration and motor control problems. An upper GI endoscopy was conducted during the patient's hospitalization after a barium swallow suggested esophageal obstruction but found no internal obstruction or any other abnormalities. Following the endoscopic procedure, the patient complained of neck aches. An anterior cervical osteophyte was subsequently discovered by computed tomography, which may have been the primary cause of the patient's dysphagia. The importance of considering coexisting medical conditions in elderly individuals, as well as the significance of promptly assessing and diagnosing dysphagia in the presence of neurodegenerative disorders such as Lewy body dementia, is emphasized by this example.

Scaffold hopping for designing of potent and selective CYP1B1 inhibitors to overcome docetaxel resistance: synthesis and evaluation.

Cytochrome P450 1B1, a tumor-specific overexpressed enzyme, significantly impairs the pharmacokinetics of several commonly used anticancer drugs including docetaxel, paclitaxel and cisplatin, leading to the problem of resistance to these drugs. Currently, there is no CYP1B1 inhibition-based adjuvant therapy available to treat this resistance problem. Hence, in the current study, exhaustive in-silico studies including scaffold hopping followed by molecular docking, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular dynamics and free energy perturbation studies were carried out to identify potent and selective CYP1B1 inhibitors. Initially, scaffold hopping analysis was performed against a well-reported potent and selective CYP1B1 inhibitor (i.e. compound 3n). A total of 200 scaffolds were identified along with their shape and field similarity scores. The top three scaffolds were further selected on the basis of these scores and their synthesis feasibility to design some potent and selective CYP1B1 inhibitors using the aforementioned in-silico techniques. Designed molecules were further synthesized to evaluate their CYP1B1 inhibitory activity and docetaxel resistance reversal potential against CYP1B1 overexpressed drug resistance MCF-7 cell line. In-vitro results indicated that compounds 2a, 2c and 2d manifested IC50 values for CYP1B1 ranging from 0.075, 0.092 to 0.088 µM with at least 10-fold selectivity. At low micromolar concentrations, compounds 1e, 1f, 2a and 2d exhibited promising cytotoxic effects in the docetaxel-resistant CYP1B1 overexpressed MCF-7 cell line. In particular, compound 2a is most effective in reversing the resistance with IC50 of 29.0 ± 3.6 µM. All of these discoveries could pave the way for the development of adjuvant therapy capable of overcoming CYP1B1-mediated resistance.Communicated by Ramaswamy H. Sarma.

Sex differences in trends and outcomes of acute myocardial infarction with mechanical complications in the United States.

BACKGROUND: Mechanical complications (MC) are rare but significant sequelae of acute myocardial infarction (AMI). Current data on sex differences in AMI with MC is limited. METHODS: We queried the National Inpatient Sample database to identify adult patients with the primary diagnosis of AMI and MC. The main outcome of interest was sex difference in-hospital mortality. Secondary outcomes were sex differences in the incidence of acute kidney injury (AKI), major bleeding, use of inotropes, permanent pacemaker implantation (PPMI), performance of percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), surgery (VSD repair and MV surgery), pericardiocentesis, use of mechanical circulatory support (MCS), ischemic stroke, and mechanical ventilation. RESULTS: Among AMI-MC cohort, in-hospital mortality was higher among females compared to males (41.24% vs 28.13%: aOR 1.39. 95% CI 1.079-1.798; p = 0.01). Among those who had VSD, females also had higher in-hospital mortality compared to males (56.7% vs 43.1%: aOR 1.74, 95% CI 1.12-2.69; p = 0.01). Females were less likely to receive CABG compared to males (12.03% vs 20%: aOR 0.49 95% CI 0.345-0.690; p < 0.001). CONCLUSION: Despite the decreasing trend in AMI admission, females had higher risk of MC and associated mortality. Significant sex disparities still exist in AMI treatment.

Omega-3 Fatty Acids for Cardiovascular Event Lowering.

Low-density lipoprotein cholesterol (LDL-C) is the main target for therapeutics aimed at reducing the risk of atherosclerotic cardiovascular disease (ASCVD) and downstream cardiovascular (CV) events. However, multiple studies have demonstrated that high-risk patient populations harbor residual risk despite effective LDL-C lowering. While data support the causal relationship between triglycerides and ASCVD risk, triglyceride-lowering therapies such as omega-3 fatty acids have shown mixed results in cardiovascular outcomes trials. Notably, icosapent ethyl, a purified formulation of eicosapentaenoic acid (EPA), has garnered compelling evidence in lowering residual cardiovascular risk in patients with hypertriglyceridemia and treated with statins. In this review, we summarize studies that have investigated omega-3-fatty acids for CV event lowering and discuss the clinical implementation of these agents based on trial data and guidelines.

Early Identification and Management of Cervical Impairments in Pediatric Patients With Concussion May Reduce Risk of Delayed Recovery.

OBJECTIVE: Previous research, including high-quality systematic reviews, has found that cervical injury, which often accompanies concussive head injury, can delay recovery from concussion. One pilot randomized controlled trial found that focused cervical assessment and appropriate intervention in children and young adults with persisting postconcussive symptoms (PPCS) improved recovery outcomes. Our sports medicine clinics adopted this approach early (within 2 weeks) in children (aged 10-18 years) after concussion. This study describes our clinical management protocol and compares the recovery trajectories in children after concussion with and without a concomitant cervical injury. DESIGN: Prospective cohort study. SETTING: Three university-affiliated outpatient sports medicine clinics from September 2016 to December 2019. PATIENTS: One-hundred thirty-four concussed children with cervical impairment (mean age 14.9 years, 65% male, and 6.2 days since concussion) were compared with 130 concussed children without cervical impairment (mean age 14.9 years, 57% male, and 6.0 days since concussion). INDEPENDENT VARIABLES: Examination findings related to the cervical spine (range of motion, cervical spasm, and cervical tenderness). MAIN OUTCOME MEASURES: Recovery time (measured in days), concussion symptom burden (Postconcussion Symptom Scale), and incidence of PPCS. RESULTS: Children with cervical impairment reported a higher initial symptom burden; however, there were no differences in recovery time (33.65 [28.20-39.09] days vs 35.98 [27.50-44.45] days, P = 0.651) or incidence of PPCS (40.0% vs 34.3%, P = 0.340). CONCLUSIONS: We conclude that within this pediatric population, early identification and management of cervical injuries concomitant with concussion may reduce the risk of delayed recovery.

Posttraumatic Stress Disorder Symptoms and Sleep Disturbances Among Asian Indians: A Systematic Review.

Substantial comorbidity exists between posttraumatic stress disorder and sleep disturbances/disorders. Such comorbidities are understudied in minority groups, including Asian Indians residing in countries outside India. Thus, we synthesized the existing literature specific to this group of Asian Indians to determine (a) prevalence estimates of posttraumatic stress disorder (PTSD) and sleep disturbances/disorders; and (b) PTSD-sleep comorbidity estimates. For this systematic review, we searched four databases (PubMed, PsycInfo, PTSDpubs, Web of Science) using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of 3,796 screened articles, 9 articles (10 studies) met inclusion criteria. Study sample sizes ranged from 11 to 2,112 Asian Indians; studies were conducted in Singapore or Malaysia. No reviewed study examined PTSD. All studies examined sleep disturbances/disorders among Asian Indians; prevalence estimates were: 8.3% to 70.4% for short sleep duration, 2.0% to 22.9% for long sleep duration, 25.9% to 56.3% for poor sleep quality, 3.4% to 67.5% for insomnia diagnosis or probable insomnia, 7.7% for excessive daytime sleepiness, 3.8% to 54.6% for obstructive sleep apnea (OSA) diagnosis or high OSA risk, and 5.1% to 11.1% for sleep-disordered breathing. Specific to Asian Indians residing in countries outside India, this review advances PTSD-sleep literature by (a) suggesting substantial prevalence of sleep disturbances/disorders; (b) highlighting the need for culturally relevant sleep interventions; and (c) highlighting research gaps (e.g., no PTSD-focused research).

Multicenter evaluation of the Selux Next-Generation Phenotyping antimicrobial susceptibility testing system.

The Selux Next-Generation Phenotyping (NGP) system (Charlestown, MA) is a new antimicrobial susceptibility testing system that utilizes two sequential assays performed on all wells of doubling dilution series to determine MICs. A multicenter evaluation of the performance of the Selux NGP system compared with reference broth microdilution was conducted following FDA recommendations and using FDA-defined breakpoints. A total of 2,488 clinical and challenge isolates were included; gram-negative isolates were tested against 24 antimicrobials, and gram-positive isolates were tested against 15 antimicrobials. Data is provided for all organism-antimicrobial combinations evaluated, including those that did and did not meet FDA performance requirements. Overall very major error and major error rates were less than 1% (31/3,805 and 107/15,606, respectively), essential agreement and categorical agreement were >95%, reproducibility was ≥95%, and the average time-to-result (from time of assay start to time of MIC result) was 5.65 hours.