Salto Talaris Fixed-Bearing Total Ankle Arthroplasty: Long-Term Results at a Mean of 10.7 Years.

Background: Total ankle arthroplasty (TAA) has become increasingly popular in the treatment for end-stage ankle arthritis in recent decades. However, there is limited evidence regarding the long-term clinical outcomes and complication rates of modern TAA implants. Methods: This study presents a follow-up on a previous cohort involving 78 patients (81 ankles) who underwent Salto Talaris fixed-bearing TAA to treat end-stage arthritis, with a mean postoperative follow-up of 5.2 years. The aim of this follow-up study was to assess the radiographic (33 patients, 35 ankles) and clinical (48 patients, 50 ankles) results from the original cohort at a mean of 10.7 years (range, 7.8-14 years). Results: At a mean of 10.7 years, the Kaplan-Meier estimated survivorship was 84.2% (95% CI, 71.9%-98.6%). For the patients reviewed, we did not find any change in patient-reported outcomes between an average 5- and 11-year follow-up. Measured total range of motion and plantarflexion did not change between 1 and 11 years, but dorsiflexion was measured as decreasing by an average of 4 degrees (P < .02). Conclusion: In this longer-term follow-up of a limited cohort, we found that Salto Talaris fixed-bearing TAA demonstrated good long-term survival with relatively low rates of revision or other complications. Patient-reported outcome and range of motion measures revealed good stability. Level of Evidence: Level III, therapeutic.

Pharmacologic Activation of STING in the Bladder Induces Potent Antitumor Immunity in Non-Muscle Invasive Murine Bladder Cancer.

Stimulator of interferon genes (STING) is an innate immune receptor activated by natural or synthetic agonists to elicit antitumoral immune response via type I IFNs and other inflammatory cytokines. Bacillus Calmette-Guerin (BCG) is the standard of care as intravesical therapy for patients with high-risk non-muscle invasive bladder cancer (NMIBC). There are limited options available for patients with NMIBC who developed BCG unresponsiveness. In this study, we characterized in vitro and in vivo antitumor effects of E7766, a macrocyle-bridged STING agonist, via intravesical instillation in two syngeneic orthotopic murine NMIBC tumor models resistant to therapeutic doses of BCG and anti-PD-1 agents. E7766 bound to recombinant STING protein with a Kd value of 40 nmol/L and induced IFNß expression in primary human peripheral blood mononuclear cells harboring any of seven major STING genotypes with EC50 values of 0.15 to 0.79 µmol/L. Intravesical E7766 was efficacious in both NMIBC models with induction of effective immunologic memory in the treated animals. Pharmacologic activation of the STING pathway in the bladder resulted in IFN pathway activation, infiltration of T cells and natural killer (NK) cells, dendritic cell activation, and antigen presentation in bladder epithelium, leading to the antitumor activity and immunity. In addition, measurements of the pharmacodynamic markers, Ifnß1 and CXCL10, in bladder, urine, and plasma, and of STING pathway intactness in cancer cells, supported this mode of action. Taken together, our studies reveal an antitumor immune effect of pharmacologic activation of the STING pathway in bladder epithelium and thus provide a rationale for subsequent clinical studies in patients with NMIBC.

Application of ISO/IEC Guide 51 to COVID-19 infection control for the occupational safety.

COVID-19 is around the world. We attempt to apply three-step method in ISO/IEC Guide 51: 2014 to COVID-19 infection control in the workplace. The results show that the COVID-19 infection control measures include the eradication of the virus, the destruction of infectivity, the detoxification and weakening and the elimination of opportunities for infection as "Inherently Safe Design Measures", the avoidance of contact as "Safeguarding and Complementary Protective Measures" and the reduction of contact and the avoidance of seriousness as "Information for Use". Among these specific measures, the New Normal, especially in the manufacturing industries, would be "telecommuting" and "unmanned workplaces", which are part of the elimination of opportunities for infection, and "changes in flow lines" and "changes in airflow", which are part of the avoidance of contact. Where "telecommuting" and "unmanned workplaces" are feasible, they should be implemented as much as possible, and where they are not, attempts should be made to minimize human-to-human contact by "changes in flow lines". In addition, in the area of "changes in airflow", there are high expectations for future research on how to establish a ventilation design for COVID-19, in which but also the source would be workers themselves, not only combustible gases and toxic gases.

E7766, a Macrocycle-Bridged Stimulator of Interferon Genes (STING) Agonist with Potent Pan-Genotypic Activity.

A strategy for creating potent and pan-genotypic stimulator of interferon genes (STING) agonists is described. Locking a bioactive U-shaped conformation of cyclic dinucleotides by introducing a transannular macrocyclic bridge between the nucleic acid bases leads to a topologically novel macrocycle-bridged STING agonist (MBSA). In addition to substantially enhanced potency, the newly designed MBSAs, exemplified by clinical candidate E7766, exhibit broad pan-genotypic activity in all major human STING variants. E7766 is shown to have potent antitumor activity with long lasting immune memory response in a mouse liver metastatic tumor model. Two complementary stereoselective synthetic routes to E7766 are also described.

End-stage renal disease increases risk of postoperative complications after lower extremity fracture.

INTRODUCTION: End-stage renal disease (ESRD) leads to multiple systemic effects and patients suffer from multiple comorbidities including fractures. While previous studies have examined complications following hip fracture surgery in ESRD patients, there are no studies evaluating other lower extremity fractures. This study aimed to identify postoperative complication risk in patients with ESRD who had lower extremity fractures. METHODS: Using our database from 2000 to 2015 at two level-one trauma centres, we collected data on patients over age 40, who had lower extremity fractures and surgical fixation. Diagnosis of ESRD was made before the injury. Each ESRD patient was matched by two non-ESRD patients regarding age, gender, American Society of Anaesthesiologists (ASA) score, and AO/OTA fracture classification. Postoperative outcomes were non-union, mechanical failure, and infection. The number of outcome events was compared between the ESRD and non-ESRD cohorts. RESULTS: A total of 195 patients (65 ESRD patients matched to 130 non-ESRD patients) were identified. Median follow-up was 31 months (12-141 months). Patients with ESRD were 3.6 time more likely to have at least one postoperative complication (mechanical failure, non-union, or infection) compared to non-ESRD patients (9/65 vs. 5/130, p = 0.02). In particular, mechanical failure was eight times higher among ESRD patients compared to non-ESRD patients (8/65 vs. 2/130, p < 0.01). CONCLUSIONS: ESRD was associated with higher rates of complications, especially mechanical failure, after lower extremity fracture surgeries.

Linked Double-Row Equivalent Arthroscopic Rotator Cuff Repair Leads to Significantly Improved Patient Outcomes.

BACKGROUND: Biomechanical studies have demonstrated that arthroscopic rotator cuff repair using a linked double-row equivalent construct results in significantly higher load to failure compared with conventional transosseous-equivalent constructs. PURPOSE: To determine the patient-reported outcomes (PROs), reoperation rates, and complication rates after linked double-row equivalent rotator cuff repair for full-thickness rotator cuff tears. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Consecutive patients who underwent linked double-row equivalent arthroscopic rotator cuff repair with minimum 2-year follow-up were included. The primary outcome was the American Shoulder and Elbow Surgeons (ASES) score at final follow-up. Secondary outcomes included the Simple Shoulder Test (SST), shortened Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire, visual analog scale (VAS), reoperations, and complications. Clinical relevance was defined by the minimally clinically important difference (MCID). Comparisons on an individual level that exceeded MCID (individual-level scores) were deemed clinically relevant. Comparisons between preoperative and postoperative scores were completed using the Student t test. All P values were reported with significance set at P < .05. RESULTS: A total of 42 shoulders in 41 consecutive patients were included in this study (21 male patients [51.2%]; mean age, 64.5 ± 11.9 years; mean follow-up, 29.7 ± 4.5 months). All patients (100%) completed the minimum 2-year follow-up. The rotator cuff tear measured on average 15.2 ± 8.9 mm in the coronal plane and 14.6 ± 9.8 mm in the sagittal plane. The ASES score improved significantly from 35.5 ± 18.2 preoperatively to 93.4 ± 10.6 postoperatively (P < .001). The QuickDASH (P < .001), SST (P < .001), and VAS (P < .001) scores also significantly improved after surgery. All patients (42/42 shoulders; 100%) achieved clinically relevant improvement (met or exceeded MCID) on ASES and SST scores postoperatively. There were no postoperative complications (0.0%) or reoperations (0.0%) at final follow-up. CONCLUSION: Arthroscopic repair of full-thickness rotator cuff tears with the linked double-row equivalent construct results in statistically significant and clinically relevant improvements in PRO scores with low complication rates (0.0%) and reoperation rates (0.0%) at short-term follow-up.

Insurance Status Affects Complication Rates After Total Hip Arthroplasty.

INTRODUCTION: Previous studies have examined the relationship between total hip arthroplasty (THA) and insurance status in small cohorts. This study evaluates the effect of patient insurance status on complications after primary elective THA using the Nationwide Inpatient Sample. METHODS: All patients undergoing primary elective THA from 1998 to 2011 were included. Patient demographics, comorbidities, and complications were collected and compared based on insurance type. Multivariable logistic regression and a matched cohort analysis were performed. RESULTS: About 515,037 patients (53.7% Medicare, 40.1% private insurance, 3.9% Medicaid/uninsured, and 2.2% other) were included, who underwent elective THA. Privately insured patients had fewer medical complications (odds ratio, 0.80; P < 0.001), whereas patients with Medicaid or no insurance demonstrated no notable difference (odds ratio, 1.03; P = 0.367) compared with Medicare patients. Similar trends were found for both surgical complications and mortality, favoring lower complication rates for privately insured patients. Furthermore, patients with private insurance tend to go to higher volume hospitals for total hip replacement surgery compared to those with Medicare insurance. DISCUSSION: Patients with government-sponsored insurance (Medicare or Medicaid) or no insurance have higher risk of medical complications, surgical complications, and mortality after primary elective THA compared with privately insured patients. Insurance status should be considered an independent risk factor for stratifying patients before THA procedures.

Insurance Status Affects In-Hospital Complication Rates After Total Knee Arthroplasty.

Insurance status has been shown to be a predictor of patient morbidity and mortality. The purpose of this study was to evaluate the effect of patient insurance status on the in-hospital complication rates following total knee arthroplasty. Data were obtained from the Nationwide Inpatient Sample (2004 through 2011). Patient demographics and comorbidities were analyzed and stratified by insurance type. Analysis was performed with a matched cohort comparing complication rates between patients with Medicare vs private insurance using the coarsened exact matching algorithm and multivariable logistic regression. A total of 1,352,505 patients (Medicare, 57.8%; private insurance, 35.6%; Medicaid/uninsured, 3.1%; other, 3.3%; unknown, 0.2%) fulfilled the inclusion criteria. The matched cohort analysis comparing Medicare with privately insured patients showed significantly higher risk of mortality (relative risk [RR], 1.34; P<.001), wound dehiscence (RR, 1.32; P<.001), central nervous system complications (RR, 1.16; P=.030), and gastrointestinal complications (RR, 1.13; P<.001) in Medicare patients, whereas privately insured patients had a higher risk of cardiac complications (RR, 0.93; P=.003). Independent of insurance status, older patients and patients with an increased comorbidity index were also associated with a higher complication rate and mortality following total knee arthroplasty. These data suggest that insurance status may be considered as an independent risk factor for increased complications when stratifying patients preoperatively for total knee replacement. Further research is needed to investigate the disparities in these findings to optimize patient outcomes following total knee arthroplasty. [Orthopedics. 2018; 41(3):e340-e347.].

Prediction Model of In-Hospital Mortality After Hip Fracture Surgery.

OBJECTIVES: Mortality in elderly patients after the surgical treatment of hip fractures remains high. Although individual clinical risk factors have been widely studied, there has been limited research on prediction models in this population. The purpose of this study was to develop a prediction model for in-hospital mortality after hip fracture surgery and to evaluate the performance of this model. METHODS: Using the National Inpatient Sample database from 2012 to 2013, we collected data on 535,475 patients older than 50 years who had hip fracture surgery. Patient characteristics, surgery-specific factors, and Elixhauser comorbidities were used as candidate variables. The patients were randomly divided into training and testing cohorts. The Lasso (least absolute shrinkage and selection operator) method was used to select predictor variables, and points were assigned to each variable based on its coefficient. RESULTS: We identified 8 essential predictors (age, timing of surgery, male sex, congestive heart failure, pulmonary circulation disease, renal failure, weight loss, and fluid and electrolyte disorders) for mortality, with a maximum prediction score of 20. The model's area under the curve was 0.74, and the Hosmer-Lemeshow test P value was 0.59 on the testing set. With the application of cutoff values (scores 0-5, 6-9, and 10-20), the observed in-hospital postoperative mortality was 0.6%, 2.5%, and 7.5%, respectively. CONCLUSIONS: We built a simple prediction model with 8 essential clinical factors that predict in-hospital mortality after hip fracture surgery. This model may assist in counseling patients and families and measuring hospital quality of care. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Weight loss after bariatric surgery in obese adolescents: a systematic review and meta-analysis.

Of adolescents in the United States, 20% have obesity and current treatment options prioritize intensive lifestyle interventions that are largely ineffective. Bariatric surgery is increasingly being offered to obese adolescent patients; however, large-scale effectiveness data is lacking. We used MEDLINE, Embase, and Cochrane databases, and a manual search of references to conduct a systematic review and meta-analysis on overall weight loss after gastric band, gastric sleeve, and gastric bypass in obese adolescent patients (age ≤19) and young adults (age ≤21) in separate analyses. We provided estimates of absolute change in body mass index (BMI, kg/m2) and percent excess weight loss across 4 postoperative time points (6, 12, 24, and 36 mo) for each surgical subgroup. Study quality was assessed using a 10 category scoring system. Data were extracted from 24 studies with 4 having multiple surgical subgroups (1 with 3, and 3 with 2 subgroups), totaling 29 surgical subgroup populations (gastric band: 16, gastric sleeve: 5, gastric bypass: 8), and 1928 patients (gastric band: 1010, gastric sleeve: 139, gastric bypass: 779). Mean preoperative BMI (kg/m2) was 45.5 (95% confidence interval [CI]: 44.7, 46.3) in gastric band, 48.8 (95%CI: 44.9, 52.8) in gastric sleeve, and 53.3 (95%CI: 50.2, 56.4) in gastric bypass patients. The short-term weight loss, measured as mean (95%CI) absolute change in BMI (kg/m2) at 6 months, was -5.4 (-3.0, -7.8) after gastric band, -11.5 (-8.8, -14.2) after gastric sleeve, and -18.8 (-10.9, -26.6) after gastric bypass. Weight loss at 36 months, measured as mean (95%CI) absolute change in BMI (kg/m2) was -10.3 (-7.0, -13.7) after gastric band, -13.0 (-11.0, -15.0) after gastric sleeve, and -15.0 (-13.5, -16.5) after gastric bypass. Bariatric surgery in obese adolescent patients is effective in achieving short-term and sustained weight loss at 36 months; however, long-term data remains necessary to better understand its long-term efficacy.

A Histologic Categorization of Aqueous Outflow Routes in Familial Open-Angle Glaucoma and Associations With Mutations in the MYOC Gene in Japanese Patients.

Purpose: This study evaluated specific relationships between pathogenic mechanisms and genetic polymorphisms in primary open-angle glaucoma (POAG). We analyzed the morphologies of trabeculectomy specimens obtained from patients with familial POAG. Methods: We used light microscopy and transmission electron microscopy to examine specimens obtained from 17 eyes of 14 patients with familial POAG. We also conducted exome analyses of two families and used targeted Sanger sequencing to analyze samples obtained from the remaining patients. Results: The POAG cases examined in this study were divided into two groups based on morphologic characteristics. Group A eyes (7 eyes from 5 patients) had an abnormally thick trabecular meshwork (TM), whereas group B eyes (10 eyes from 9 patients) had a TM of normal thickness. The characteristics of the outflow routes in group A eyes were remarkable and included apoptotic TM cells, abnormally thickened TM basement membranes, fused TM beams, and occluded Schlemm's canals. All group A patients harbored mutations (F369L, P370L, T377M, and T448P) in the myocilin (MYOC) gene that were not found in group B patients. Conclusions: Although age matching of morphologic changes in the outflow routes was impossible due to the small sample size, this study suggests that abnormal TM cells may cause sequential damage in abnormally thickened TM basement membranes, TM cell apoptosis, TM beam fusion, and the occlusion of Schlemm's canals. The four detected MYOC mutations appeared to be associated with morphologic changes in the TM and the underlying pathogenesis of a subtype of familial POAG.

Stereoselective synthesis of the Halaven C14-C26 fragment from D-quinic acid: crystallization-induced diastereoselective transformation of an α-methyl nitrile.

Crystallization-induced diastereoselective transformation (CIDT) of an α-methyl nitrile completes an entirely non-chromatographic synthesis of the halichondrin B C14-C26 stereochemical array. The requisite α-methyl nitrile substrate is derived from D-quinic acid through a series of substrate-controlled stereoselective reactions via a number of crystalline intermediates that benefit from a rigid polycyclic template. Therefore, all four stereogenic centers in the Halaven C14-C26 fragment were derived from the single chiral source D-quinic acid.

Total synthesis of 6-deoxypladienolide D and Assessment of Splicing Inhibitory Activity in a Mutant SF3B1 cancer cell line.

A total synthesis of the natural product 6-deoxypladienolide D (1) has been achieved. Two noteworthy attributes of the synthesis are (1) a late-stage allylic oxidation which proceeds with full chemo-, regio-, and diastereoselectivity and (2) the development of a scalable and cost-effective synthetic route to support drug discovery efforts. 6-Deoxypladienolide D (1) demonstrates potent growth inhibition in a mutant SF3B1 cancer cell line, high binding affinity to the SF3b complex, and inhibition of pre-mRNA splicing.

Influence of horizontal condylar angle and x-ray projection angle on the appearance of the condyle on lateral temporomandibular joint panoramic radiographs.

AIMS: This study used dried human mandibles and aimed to assess the effect of different horizontal condylar angle and the effect of different beam angles from three different units in the depiction of medial, central and lateral parts of the condyle on panoramic and lateral temporomandibular joint (TMJ) panoramic images. METHODS: Standard panoramic and lateral TMJ panoramic images of four dried human mandibles with horizontal condylar angles of 5, 8,10, 15, 17 and 20 degrees were analysed. The different parts of the condyle were represented by radiopaque markers. The standard panoramic and lateral TMJ panoramic images of the four mandibles were acquired from three panoramic radiography models with different x-ray beam angle. The images were analysed for the position of these radiopaque markers. RESULTS: Standard panoramic images demonstrated almost similar images of the condyles in the three panoramic models. The lateral TMJ panoramic images demonstrated the medial pole anterior to the lateral pole when the x-ray projection angle was more than the horizontal condylar angle; superimposition of medial and lateral poles when the x-ray projection angle was equal to horizontal condylar angle; and lateral pole anterior to medial pole when the x-ray projection angle was less than beam projection angle. CONCLUSION: This study demonstrated that apart from other factors, the depiction of the mandibular condyle on lateral TMJ panoramic radiographs depends on the horizontal condylar angle, and the x-ray beam angle, which differs among different manufacturers. Therefore these limitations have to be considered when interpreting the integrity of the mandibular condyle on lateral TMJ panoramic radiographs.

Preparation and evaluation of unimolecular pentavalent and hexavalent antigenic constructs targeting prostate and breast cancer: a synthetic route to anticancer vaccine candidates.

Several novel, fully synthetic, carbohydrate-based antitumor vaccines have been assembled. Each construct consists of multiple cancer-related antigens displayed on a single polypeptide backbone. Recent advances in synthetic methodology have allowed for the incorporation of a complex oligosaccharide terminating in a sialic acid residue (i.e., GM2) as one of the carbohydrate antigens. Details of the vaccine synthesis as well as the results of preliminary immunological investigations are described herein.

Physical properties and ease of operation of a wireless intraoral x-ray sensor.

OBJECTIVE: A wireless CMOS (CDR Wireless) system was evaluated based on its physical properties and ease of operation. STUDY DESIGN: The physical properties were assessed by dose-response curve, modulation transfer function, and detective quantum efficiency tests. The range of signal receptivity between the sensor and the antenna was also determined. The time required to make a radiograph was measured. Using a visual analog scale (VAS), 10 test patients were asked to evaluate the discomfort caused by having the sensor inserted and placed in the mouth. An intraoral x-ray film packet and a wired CDR sensor were also evaluated for comparison with the wireless system. RESULTS: The physical properties of the wireless system and the wired CDR sensor were essentially equal. The antenna could receive the signal up to 3.5 m from the sensor. The wireless CMOS system required less time to perform the radiographic task than the other methods studied. The VAS scores for the wireless and wired CDR sensors were comparable. CONCLUSIONS: The CDR Wireless sensor has equivalent physical properties to its wired counterpart and may be more convenient to use.