Abstract: Sepsis Associated Kidney Injury represents a major health concern as it is frequently associated with increased risk of mortality and morbidity. We aimed to evaluate the potential value of TNF-α (−376 G/A) and cystatin C in the diagnosis of S-AKI and prediction of mortality in critically ill patients. This study included 200 critically ill patients and 200 healthy controls. Patients were categorized into 116 with acute septic shock and 84 with sepsis, from which 142 (71%) developed S-AKI. Genotyping of TNF-α (−376 G/A) was performed by RT-PCR and serum CysC was assessed by Enzyme Linked Immunosorbent Assay. Our results showed a highly significant difference in the genotype frequencies of TNF-α (−376 G/A) SNP between S-AKI and non-AKI patients ( p & lt; 0.001). Additionally, sCysC levels were significantly higher in the S-AKI group ( p = 0.011). The combination of both sCysC and TNF-α (−376 G/A) together had a better diagnostic ability for S-AKI than sCysC alone (AUC = 0.610, 0.838, respectively). Both GA and AA genotypes were independent predictors of S-AKI ( p = & lt; 0.001, p = 0.002 respectively). Additionally, sCysC was significantly associated with the risk of S-AKI development (Odds Ratio = 1.111). Both genotypes and sCysC were significant predictors of non-survival ( p & lt; 0.001), suggesting their potential role in the diagnosis of S-AKI and prediction of mortality.

Abstract: Condensation of 3-acetyl-8-ethoxycoumarin (3) with thiosemicarbazide gave ethylidenehydrazinecarbothioamide 5, which was transformed into the thiazolidin-4-one derivatives 6,7. Interaction of 3 with DMF/POCl3 gave b-chloroacroline derivative 8. Treatment of 3 with malononitrile gave benzo[c]chromone and 2-aminobenzonitrile derivatives 9 and 10, respectively with respect to the reaction conditions. Condensation of 3-(2-bromoacetyl)-8-ethoxycoumarin (4) with o-phenylenediamine gave 3-(quioxaline-2-yl)-8-ethoxycoumarin hydrobromide (11), while 4 reacted with 2-aminopyridine to give chromenopyridopyrimidine derivative 12. Condensation of 4 with potassium thio-cyanate/methanol gave an unexpected derivative, 2H-chromeno-3-carboxy(methyl-carbonimidic)thioanhydride 16, which upon treatment with (NH2)2·H2O gave 3-ethoxy-2-hydroxybenzaldehyde azine 19. Interaction of 4 with thiourea derivatives gave thiazole derivatives 20a–c. The structures of the newly synthesized compounds were confirmed by their spectra data. The newly synthesized compounds were also screened for their antimicrobial activity.

Abstract: Patient-reported outcome measures (PROMs), including the Patient-reported Outcomes Measurement Information System (PROMIS), are increasingly used to measure healthcare value. The minimum clinically important difference (MCID) is a metric that helps clinicians determine whether a statistically detectable improvement in a PROM after surgical care is likely to be large enough to be important to a patient or to justify an intervention that carries risk and cost. There are two major categories of MCID calculation methods, anchor-based and distribution-based. This variability, coupled with heterogeneous surgical cohorts used for existing MCID values, limits their application to clinical care. Questions/purposes In our study, we sought (1) to determine MCID thresholds and attainment percentages for PROMIS after common orthopaedic procedures using distribution-based methods, (2) to use anchor-based MCID values from published studies as a comparison, and (3) to compare MCID attainment percentages using PROMIS scores to other validated outcomes tools such as the Hip Disability and Osteoarthritis Outcome Score (HOOS) and Knee Disability and Osteoarthritis Outcome Score (KOOS). Methods This was a retrospective study at two academic medical centers and three community hospitals. The inclusion criteria for this study were patients who were age 18 years or older and who underwent elective THA for osteoarthritis, TKA for osteoarthritis, one-level posterior lumbar fusion for lumbar spinal stenosis or spondylolisthesis, anatomic total shoulder arthroplasty or reverse total shoulder arthroplasty for glenohumeral arthritis or rotator cuff arthropathy, arthroscopic anterior cruciate ligament reconstruction, arthroscopic partial meniscectomy, or arthroscopic rotator cuff repair. This yielded 14,003 patients. Patients undergoing revision operations or surgery for nondegenerative pathologies and patients without preoperative PROMs assessments were excluded, leaving 9925 patients who completed preoperative PROMIS assessments and 9478 who completed other preoperative validated outcomes tools (HOOS, KOOS, numerical rating scale for leg pain, numerical rating scale for back pain, and QuickDASH). Approximately 66% (6529 of 9925) of patients had postoperative PROMIS scores (Physical Function, Mental Health, Pain Intensity, Pain Interference, and Upper Extremity) and were included for analysis. PROMIS scores are population normalized with a mean score of 50 ± 10, with most scores falling between 30 to 70. Approximately 74% (7007 of 9478) of patients had postoperative historical assessment scores and were included for analysis. The proportion who reached the MCID was calculated for each procedure cohort at 6 months of follow-up using distribution-based MCID methods, which included a fraction of the SD (1/2 or 1/3 SD) and minimum detectable change (MDC) using statistical significance (such as the MDC 90 from p 〈 0.1). Previously published anchor-based MCID thresholds from similar procedure cohorts and analogous PROMs were used to calculate the proportion reaching MCID. Results Within a given distribution-based method, MCID thresholds for PROMIS assessments were similar across multiple procedures. The MCID threshold ranged between 3.4 and 4.5 points across all procedures using the 1/2 SD method. Except for meniscectomy (3.5 points), the anchor-based PROMIS MCID thresholds (range 4.5 to 8.1 points) were higher than the SD distribution-based MCID values (2.3 to 4.5 points). The difference in MCID thresholds based on the calculation method led to a similar trend in MCID attainment. Using THA as an example, MCID attainment using PROMIS was achieved by 76% of patients using an anchor-based threshold of 7.9 points. However, 82% of THA patients attained MCID using the MDC 95 method (6.1 points), and 88% reached MCID using the 1/2 SD method (3.9 points). Using the HOOS metric (scaled from 0 to 100), 86% of THA patients reached the anchor-based MCID threshold (17.5 points). However, 91% of THA patients attained the MCID using the MDC 90 method (12.5 points), and 93% reached MCID using the 1/2 SD method (8.4 points). In general, the proportion of patients reaching MCID was lower for PROMIS than for other validated outcomes tools; for example, with the 1/2 SD method, 72% of patients who underwent arthroscopic partial meniscectomy reached the MCID on PROMIS Physical Function compared with 86% on KOOS. Conclusion MCID calculations can provide clinical correlation for PROM scores interpretation. The PROMIS form is increasingly used because of its generalizability across diagnoses. However, we found lower proportions of MCID attainment using PROMIS scores compared with historical PROMs. By using historical proportions of attainment on common orthopaedic procedures and a spectrum of MCID calculation techniques, the PROMIS MCID benchmarks are realizable for common orthopaedic procedures. For clinical practices that routinely collect PROMIS scores in the clinical setting, these results can be used by individual surgeons to evaluate personal practice trends and by healthcare systems to quantify whether clinical care initiatives result in meaningful differences. Furthermore, these MCID thresholds can be used by researchers conducting retrospective outcomes research with PROMIS. Level of Evidence Level III, therapeutic study.

Abstract: TKA and THA are major surgical procedures, and they are associated with the potential for serious, even life-threatening complications. Patients must weigh the risks of these complications against the benefits of surgery. However, little is known about the relative importance patients place on the potential complications of surgery compared with any potential benefit the procedures may achieve. Furthermore, patient preferences may often be discordant with surgeon preferences regarding the treatment decision-making process. A discrete-choice experiment (DCE) is a quantitative survey technique designed to elicit patient preferences by presenting patients with two or more hypothetical scenarios. Each scenario is composed of several attributes or factors, and the relative extent to which respondents prioritize these attributes can be quantified to assess preferences when making a decision, such as whether to pursue lower extremity arthroplasty. Questions/purposes In this DCE, we asked: (1) Which patient-related factors (such as pain and functional level) and surgery-related factors (such as the risk of infection, revision, or death) are influential in patients’ decisions about whether to undergo lower extremity arthroplasty? (2) Which of these factors do patients emphasize the most when making this decision? Methods A DCE was designed with the following attributes: pain; physical function; return to work; and infection risks, reoperation, implant failure leading to premature revision, deep vein thrombosis, and mortality. From October 2021 to March 2022, we recruited all new patients to two arthroplasty surgeons’ clinics who were older than 18 years and scheduled for a consultation for knee- or hip-related complaints who had no previous history of a primary TKA or THA. A total of 56% (292 of 517) of new patients met the inclusion criteria and were approached with the opportunity to complete the DCE. Among the cohort, 51% (150 of 292) of patients completed the DCE. Patients were administered the DCE, which consisted of 10 hypothetical scenarios that had the patient decide between a surgical and nonsurgical outcome, each consisting of varying levels of eight attributes (such as infection, reoperation, and ability to return to work). A subsequent demographic questionnaire followed this assessment. To answer our first research question about the patient-related and surgery-related factors that most influence patients’ decisions to undergo lower extremity arthroplasty, we used a conditional logit regression to control for potentially confounding attributes from within the DCE and determine which variables shifted a patient’s determination to pursue surgery. To answer our second question, about which of these factors received the greatest priority by patients, we compared the relevant importance of each factor, as determined by each factor’s beta coefficient, against each other influential factor. A larger absolute value of beta coefficient reflects a relatively higher degree of importance placed on a variable compared with other variables within our study. Of the respondents, 57% (85 of 150) were women, and the mean age at the time of participation was 64 ± 10 years. Most respondents (95% [143 of 150] ) were White. Regarding surgery, 38% (57 of 150) were considering THA, 59% (88 of 150) were considering TKA, and 3% (5 of 150) were considering both. Among the cohort, 49% (74 of 150) of patients reported their average pain level as severe, or 7 to 10 on a scale from 0 to 10, and 47% (71 of 150) reported having 50% of full physical function. Results Variables that were influential to respondents when deciding on lower extremity total joint arthroplasty were improvement from severe pain to minimal pain (β coefficient: -0.59 [95% CI -0.72 to -0.46]; p 〈 0.01), improvement in physical function level from 50% to 100% (β: -0.80 [95% CI -0.9 to -0.7]; p 〈 0.01), ability to return to work versus inability to return (β: -0.38 [95% CI -0.48 to -0.28]; p 〈 0.01), and the surgery-related factor of risk of infection (β: -0.22 [95% CI -0.30 to -0.14]; p 〈 0.01). Improvement in physical function from 50% to 100% was the most important for patients making this decision because it had the largest absolute coefficient value of -0.80. To improve physical function from 50% to 100% and reduce pain from severe to minimal because of total joint arthroplasty, patients were willing to accept a hypothetical absolute (and not merely an incrementally increased) 37% and 27% risk of infection, respectively. When we stratified our analysis by respondents’ preoperative pain levels, we identified that only patients with severe pain at the time of their appointment found the risk of infection influential in their decision-making process (β: -0.27 [95% CI -0.37 to -0.17]; p = 0.01) and were willing to accept a 24% risk of infection to improve their physical functioning from 50% to 100%. Conclusion Our study revealed that patients consider pain alleviation, physical function improvement, and infection risk to be the most important attributes when considering total joint arthroplasty. Patients with severe baseline pain demonstrated a willingness to take on a hypothetically high infection risk as a tradeoff for improved physical function or pain relief. Because patients seemed to prioritize postoperative physical function so highly in our study, it is especially important that surgeons customize their presentations about the likelihood an individual patient will achieve a substantial functional improvement as part of any office visit where arthroplasty is discussed. Future studies should focus on quantitatively assessing patients’ understanding of surgical risks after a surgical consultation, especially in patients who may be the most risk tolerant. Clinical Relevance Surgeons should be aware that patients with the most limited physical function and the highest baseline pain levels are more willing to accept the more potentially life-threatening and devastating risks that accompany total joint arthroplasty, specifically infection. The degree to which patients seemed to undervalue the harms of infection (based on our knowledge and perception of those harms) suggests that surgeons need to take particular care in explaining the degree to which a prosthetic joint infection can harm or kill patients who develop one.