Surgeon preferences in the treatment of thumb carpometacarpal osteoarthritis.

BACKGROUND: Primary thumb carpometacarpal (CMC) osteoarthritis is one of the most common conditions encountered by hand surgeons. Of the vast number of operations that have been proposed, none have demonstrated results significantly superior to trapeziectomy alone. AIM: The purpose of our study was to determine why surgeons opt for their technique in treating CMC arthritis. METHODS: A cross-sectional survey of active members of the American Society for Surgery of the Hand was conducted to evaluate the reasons behind their preferred technique in the treatment of isolated thumb CMC arthritis. Surgeons were contacted by e-mail once and provided with a link to a de-identified survey consisting of 5 treatment questions and 5 demographic questions. RESULTS: Of 950 responses were received. 40.5% of surgeons preferred trapeziectomy + ligament reconstruction tendon interposition (LRTI), followed by trapeziectomy + suspensionplasty (28.2%), suture button suspension (5.9 %), trapeziectomy alone (4.6%), prosthetic arthroplasty (3.2%), arthrodesis (1.1%), and other (6.6%). Proponents of trapeziectomy + LRTI cited familiarity (73.2%), exposure during fellowship (48.8%) and less proximal migration (60%) to be the main reasons affecting their decision. Surgeons who preferred trapeziectomy + suspensionplasty most reported simplicity (74.9%), fewer complications (45.3%), less proximal migration (43.8%), and avoidance of autogenous tissue harvest (42.7%). Advocates of suture button suspension cited avoidance of autogenous tissue harvest (80.4%), shorter immobilization (76.8%), and quicker recovery (73.2%) with their technique. Advocates of trapeziectomy alone cited simplicity (97.7%), fewer complications (86.4%), and avoidance of autogenous tissue harvest (59.1%). In their comments, 45% of surgeons choosing trapeziectomy alone cited evidence as an additional rationale. Advocates of prosthetic arthroplasty cited improved pinch strength (83.3%) and improved range of motion (63.3%), while those preferring arthrodesis cited better pinch strength (90%) and frequently in their comments, durability. Of the surgeons who preferred a technique other than LRTI, 41.8% reported they had tried LRTI in the past, citing complexity of the procedure, flexor carpi radialis harvest, and longer operative time as reasons for moving on. CONCLUSION: Our study provides an update on current treatment trends and offers new insight into the reasons behind surgeons' decision making in the management of thumb carpometacarpal osteoarthritis. Despite strong Level 1 evidence supporting the use of trapeziectomy alone, our findings demonstrate that most surgeons continue to supplement trapeziectomy with other techniques such as LRTI or suspensionplasty. Several factors including familiarity, personal experience (Level 4 evidence), and comfort may be more influential than Level 1 evidence in determining the techniques in a surgeon's armamentarium. Further prospective studies are needed to determine the optimal technique for surgical management of Eaton stages II-IV CMC arthritis and how these studies will affect surgeons' choice.

Clinical Decision Support for Hypertension Management in Chronic Kidney Disease: A Randomized Clinical Trial.

Importance: Chronic kidney disease (CKD) affects 37 million adults in the United States, and for patients with CKD, hypertension is a key risk factor for adverse outcomes, such as kidney failure, cardiovascular events, and death. Objective: To evaluate a computerized clinical decision support (CDS) system for the management of uncontrolled hypertension in patients with CKD. Design, Setting, and Participants: This multiclinic, randomized clinical trial randomized primary care practitioners (PCPs) at a primary care network, including 15 hospital-based, ambulatory, and community health center-based clinics, through a stratified, matched-pair randomization approach February 2021 to February 2022. All adult patients with a visit to a PCP in the last 2 years were eligible and those with evidence of CKD and hypertension were included. Intervention: The intervention consisted of a CDS system based on behavioral economic principles and human-centered design methods that delivered tailored, evidence-based recommendations, including initiation or titration of renin-angiotensin-aldosterone system inhibitors. The patients in the control group received usual care from PCPs with the CDS system operating in silent mode. Main Outcomes and Measures: The primary outcome was the change in mean systolic blood pressure (SBP) between baseline and 180 days compared between groups. The primary analysis was a repeated measures linear mixed model, using SBP at baseline, 90 days, and 180 days in an intention-to-treat repeated measures model to account for missing data. Secondary outcomes included blood pressure (BP) control and outcomes such as percentage of patients who received an action that aligned with the CDS recommendations. Results: The study included 174 PCPs and 2026 patients (mean [SD] age, 75.3 [0.3] years; 1223 [60.4%] female; mean [SD] SBP at baseline, 154.0 [14.3] mm Hg), with 87 PCPs and 1029 patients randomized to the intervention and 87 PCPs and 997 patients randomized to usual care. Overall, 1714 patients (84.6%) were treated for hypertension at baseline. There were 1623 patients (80.1%) with an SBP measurement at 180 days. From the linear mixed model, there was a statistically significant difference in mean SBP change in the intervention group compared with the usual care group (change, -14.6 [95% CI, -13.1 to -16.0] mm Hg vs -11.7 [-10.2 to -13.1] mm Hg; P = .005). There was no difference in the percentage of patients who achieved BP control in the intervention group compared with the control group (50.4% [95% CI, 46.5% to 54.3%] vs 47.1% [95% CI, 43.3% to 51.0%]). More patients received an action aligned with the CDS recommendations in the intervention group than in the usual care group (49.9% [95% CI, 45.1% to 54.8%] vs 34.6% [95% CI, 29.8% to 39.4%]; P < .001). Conclusions and Relevance: These findings suggest that implementing this computerized CDS system could lead to improved management of uncontrolled hypertension and potentially improved clinical outcomes at the population level for patients with CKD. Trial Registration: ClinicalTrials.gov Identifier: NCT03679247.

Prospective Analysis of Simulated Pneumatic Tourniquet Use and Oedema Following Axillary Lymph Node Dissection.

Background: Tourniquet use during upper extremity surgery in patients with a history of axillary lymph node dissection (ALND) remains controversial due to the perceived but unproven risk of lymphoedema. We prospectively evaluated upper extremity swelling in patients with a history of unilateral ALND using a standardised tourniquet model. Methods: A tourniquet was applied to the upper arm bilaterally, with the unaffected side serving as an internal control. Each arm was subsequently held in an elevated position to reduce swelling. Hand volume was measured using an aqueous volumeter. Results: The patients' ALND arms experienced slightly greater increases in volume following tourniquet application compared to their healthy control arms. However, this amount of oedema was temporary and reversible, as both arms experienced spontaneous resolution of swelling with no significant difference in residual hand volume at the conclusion of the study. Conclusions: Tourniquet use may be safe in patients with a history of ALND. Further investigation is needed to verify this in a surgical setting. Level of Evidence: Level II (Therapeutic).

Preoperative and Intraoperative Urine Cultures and Its Association With Postoperative Infection After Ureteroneocystostomy.

OBJECTIVE: To unveil this association, we hypothesize that preoperative and intraoperative urinary tract infection (UTI) will be correlated with postoperative UTI and sepsis occurrence. PATIENTS AND METHODS: The 2020 National Surgical Quality Improvement Program Pediatric (NSQIP-P) data was analyzed for patients undergoing ureteroneocystostomy (UNC) for vesicoureteral reflux (VUR). Patients that underwent UNC for treatment of VUR with urine culture obtained within 2weeks preoperatively or on the day of surgery were identified. The patients were divided into 3 groups: no bacterial growth, bacterial growth with UTI, and bacterial growth polymicrobial growth. Patient demographics and preoperative variables were evaluated. RESULTS: The postoperative urinary tract infection rate of the three groups were 2.0%, 9.2%, and 9.9% for group A, B, C, respectively (P < .001). Postoperative sepsis was noted to be 0.5%, 1.3%, and 3.6% for group A, B, C (P < .01). Additionally, there was a difference between mean operative time (P < .001), mean length of stay (P = .03), and mean days from operation to discharge (P < .01). On adjusted analysis, both groups B and C had higher rates of UTI compared to group A. Group C was also seen to have greater rates of sepsis on adjusted analysis. CONCLUSION: The association found between preoperative UTI with less than 2 species of microorganisms (group B) and postoperative UTI indicates that UTI treatment and antibiotic prophylaxis should be considered when undergoing UNC for VUR. The results of this study may lead to more careful consideration of the use of preoperative and intraoperative urine culture as well as treatment of UTI in pediatric patients with VUR undergoing UNC.

Vesicoureteral reflux severity is not associated with unplanned urinary catheterization or length of hospital stay after ureteroneocystostomy.

INTRODUCTION: Vesicoureteral reflux (VUR) is a common urologic condition affecting approximately 1% of all children. Surgical success often depends on the grade of VUR, as patients with grades 4 or 5 have been have a greater risk for postoperative complications. Unplanned urinary catheter placement (UCP) postoperatively and prolonged length of hospital stay (LOS) are indicative of unexpected complications. The association between VUR severity and such metrics remain unclear. OBJECTIVE: The study's objective is to determine if the severity of VUR is associated with higher rates of UCP or prolonged LOS after ureteroneocystostomy (UNC). STUDY DESIGN: The 2020 National Surgical Quality Improvement Program Pediatric database was analyzed for patients with VUR. A total of 1742 patients were initially evaluated with 1373 meeting exclusion criteria. The patients were divided into 3 groups of varying voiding cystourethrogram (VCUG) or radionuclide cystogram (RNC) severity: VCUG Grade 1 or RNC Grade 1 (Group A), VCUG Grade 2 or 3 or RNC Grade 2 (Group B), and VCUG Grade 4 or 5 or RNC Grade 3 (Group C). Basic statistical analysis was performed, and logistic regression was performed with both UCP and LOS as dependent variables. RESULTS: Among the 1373 patients, 2.9% were included in Group A, 32.5% were in Group B, and 64.6% were in Group C. Significant differences were found among the groups for mean age, gender, inpatient status, rate of congenital malformation, ureteral stents, and ASA classification. Regarding surgical treatment, differences were also found comparing mean operative time, LOS, laterality and type of procedure, urine culture results, rates of UTI, surgical site infections, postoperative returns to the emergency department, and unplanned procedures and catheterization. Multivariate analysis demonstrated no significant association between the rate of UCP and VUR severity, while postoperative UTI and unplanned procedure were both independent factors associated with UCP postoperatively. Additionally, postoperative UTI, ASA classification, mean operation time, ureteral stent placement, unplanned procedure, and UCP were independent factors found to contribute to LOS. CONCLUSION: Greater VUR severity does not appear to increase the need for catheterization or prolong hospital stay, while the development of a UTI postoperatively or having an additional unplanned procedure are associated with an increased likelihood of both. The postoperative course after UNC also appears to be influenced more so by other factors such as the operative approach and whether complications arise.

Abuse of power in the disciplinary actions of a state psychology licensing board: inequitable outcomes and early career psychologists.

The field of psychology has established high professional standards which have become a cornerstone of the practice of psychology. However, powerful boards tasked with administering these standards can operate with little oversight, making it difficult to monitor whether these institutions are operating in a fair and impartial way. In particular, early-career psychologists who have less experience and power in their initial years of independent practice may be singularly vulnerable as they have relatively little experience to navigate the profession, including fielding complaints that may be made against them to a licensing board. While it is essential to ensure early-career psychologists are upholding their commitments to the practice, there are risks in policing their activities without orienting toward growth, learning, and professional development. Even the smallest disciplinary action may never be expunged from a psychologist's record, resulting in long-term implications for insurance coverage, reputation and future professional viability in the field. Overly-punitive approaches can be distressing or even traumatizing. In this paper, we examine disciplinary actions of the Kentucky Board of Examiners of Psychology (KBEP) from the years 2000 to 2020 (N = 65) to determine the methodology by which the Board administers its oversight function. We analyze the nature of the discipline received (fines, suspensions, continuing education, supervision) revealing a two-tiered system of punishments, and provide context regarding the nature of the disciplinary process and its impacts. We report on qualitative interviews of early career psychologists subject to disciplinary actions by the Board, and psychologists who supervised early career psychologists investigated by the Board. We compare legislation governing KBEP and make comparisons to the workings of licensing boards in three other states. Using these findings, we make recommendations for revisions to the applicable legislation and administrative processes of the Board to establish an improved balance between public safety, the well-being of new psychologists, equity considerations such as race, and the development of the practice of psychology in Kentucky. This work brings to light previously unexamined injustices that can knowingly or unknowingly be perpetuated by licensing Boards, and can be used to inform the creation of more just, balanced and inclusive professional Boards.

The effect of shoulder prosthesis stem length on failure due to torsional loading. A biomechanical study in composite humeri.

Background: Shoulder arthroplasty is becoming increasingly common. With evolving implant designs, multiple humeral stem options exist for the surgeon to choose from. New stemless and short-stem systems are modular, remove less native bone stock, and better adapt to patient anatomy. It has been suggested that shorter stem implants may be protective against periprosthetic fracture; however, this has not been mechanistically evaluated. Therefore, this study aimed to biomechanically test synthetic humeri with long-stem, short-stem, and stemless arthroplasty components in a torsional manner to evaluate their response to loading and characterize failure. Methods: Twenty-four synthetic humeri were implanted with long stem, short stem, or stemless uncemented prosthesis, 8 in each group. Humeri were mounted in a custom testing jig with a morse taper interfacing with a mechanical testing system. After a 20N axial force, specimens were torsionally loaded to failure at 15 degrees/sec, with 50 Hz collection. Torque vs. rotation curves were generated for each specimen, and stiffness, yield, ultimate strength, and failure load were measured. ANOVA and post hoc pairwise comparisons were used to assess effect of stem type on mechanical test variable. The association of the stem type with fracture type was analyzed by a Fisher's Exact test. Statistical significance was set at P < .05. Results: During torsional loading, long-stem implants were significantly stiffer than short or stemless implants. The angle of implant yielding was similar across stem designs; however, stemless implants had a lower yield torque. This correlated with a decreased yield energy in stemless compared to short stems as well. Maximum torque and failure torque was also significantly higher in short-stem and long-stem implants compared to stemless. Discussion: Periprosthetic fractures in shoulder arthroplasty are a concern in low-energy trauma, and stem design likely plays a significant role in early implant-bone failure. Our results suggest stemless implants under torsional load fail at lower stress and are less stiff than stemmed implants. The failure mechanism of stemless implants through metaphyseal cancellous bone emphasizes the effect bone quality has on implant fixation. There is likely a balance of torsional stability to survive physiologic loads while minimizing diaphyseal stress and risk of diaphyseal periprosthetic fracture. This combined with revision and fixation options represent decisions the surgeon is faced with when performing shoulder arthroplasty.

Refining Clinical Phenotypes to Improve Clinical Decision Support and Reduce Alert Fatigue: A Feasibility Study.

BACKGROUND: Chronic kidney disease (CKD) is common and associated with adverse clinical outcomes. Most care for early CKD is provided in primary care, including hypertension (HTN) management. Computerized clinical decision support (CDS) can improve the quality of care for CKD but can also cause alert fatigue for primary care physicians (PCPs). Computable phenotypes (CPs) are algorithms to identify disease populations using, for example, specific laboratory data criteria. OBJECTIVES: Our objective was to determine the feasibility of implementation of CDS alerts by developing CPs and estimating potential alert burden. METHODS: We utilized clinical guidelines to develop a set of five CPs for patients with stage 3 to 4 CKD, uncontrolled HTN, and indications for initiation or titration of guideline-recommended antihypertensive agents. We then conducted an iterative data analytic process consisting of database queries, data validation, and subject matter expert discussion, to make iterative changes to the CPs. We estimated the potential alert burden to make final decisions about the scope of the CDS alerts. Specifically, the number of times that each alert could fire was limited to once per patient. RESULTS: In our primary care network, there were 239,339 encounters for 105,992 primary care patients between April 1, 2018 and April 1, 2019. Of these patients, 9,081 (8.6%) had stage 3 and 4 CKD. Almost half of the CKD patients, 4,191 patients, also had uncontrolled HTN. The majority of CKD patients were female, elderly, white, and English-speaking. We estimated that 5,369 alerts would fire if alerts were triggered multiple times per patient, with a mean number of alerts shown to each PCP ranging from 0.07-to 0.17 alerts per week. CONCLUSION: Development of CPs and estimation of alert burden allows researchers to iteratively fine-tune CDS prior to implementation. This method of assessment can help organizations balance the tradeoff between standardization of care and alert fatigue.

Perched Anteromedial Radial Head Dislocation.

Perched anteromedial radial head dislocation is a rare injury pattern that is yet to be reported in the literature. This article describes a case report of an isolated radial head dislocation that was perched on the coronoid process. The images in this study show this rare injury pattern, which did not include a fracture of the coronoid or true elbow dislocation. The patient was successfully treated with a closed reduction. The patient regained full ROM and function. Previously described literature has failed to report this injury pattern or successful closed treatment. The success of this case demonstrates the difficulty of closed reductions even under proper anesthesia and the importance of performing them in the setting where the surgeon has the option to convert to open reduction in unsuccessful cases.

Prospective randomized controlled trial comparing the effect of Monocryl versus nylon sutures on patient- and observer-assessed outcomes following carpal tunnel surgery.

Controversy remains regarding the optimal technique and suture type for wound closure after carpal tunnel surgery. Adult patients undergoing open carpal tunnel release were prospectively randomized to receive either interrupted, buried Monocryl sutures or traditional nylon horizontal mattress sutures for their wound closures. At the 2-week and 6-week postoperative visits, Patient and Observer Scar Assessment Scale questionnaires were completed. At 2 weeks, patients and observers had a significantly better opinion of incisions closed with Monocryl. By 6 weeks, neither patients nor observers found a difference between suture types in any category. Scars of wounds closed with Monocryl did not change appreciably in appearance between 2 and 6 weeks. However, patients and observers noted significant improvement in scar appearance in the nylon group over time. Monocryl suture represents an effective method for carpal tunnel closure that leads to improved patient- and observer-reported outcome scores in the early postoperative period compared with nylon.Level of evidence: II.

Human-centered design of clinical decision support for management of hypertension with chronic kidney disease.

BACKGROUND: Primary care providers face challenges in recognizing and controlling hypertension in patients with chronic kidney disease (CKD). Clinical decision support (CDS) has the potential to aid clinicians in identifying patients who could benefit from medication changes. This study designed an alert to control hypertension in CKD patients using an iterative human-centered design process. METHODS: In this study, we present a human-centered design process employing multiple methods for gathering user requirements and feedback on design and usability. Initially, we conducted contextual inquiry sessions to gather user requirements for the CDS. This was followed by group design sessions and one-on-one formative think-aloud sessions to validate requirements, obtain feedback on the design and layout, uncover usability issues, and validate changes. RESULTS: This study included 20 participants. The contextual inquiry produced 10 user requirements which influenced the initial alert design. The group design sessions revealed issues related to several themes, including recommendations and clinical content that did not match providers' expectations and extraneous information on the alerts that did not provide value. Findings from the individual think-aloud sessions revealed that participants disagreed with some recommended clinical actions, requested additional information, and had concerns about the placement in their workflow. Following each step, iterative changes were made to the alert content and design. DISCUSSION: This study showed that participation from users throughout the design process can lead to a better understanding of user requirements and optimal design, even within the constraints of an EHR alerting system. While raising awareness of design needs, it also revealed concerns related to workflow, understandability, and relevance. CONCLUSION: The human-centered design framework using multiple methods for CDS development informed the creation of an alert to assist in the treatment and recognition of hypertension in patients with CKD.

Cost-Minimization Analysis and Treatment Trends of Surgical and Nonsurgical Treatment of Proximal Humerus Fractures.

PURPOSE: Recent evidence demonstrated similar outcomes between nonsurgical and surgical management of displaced proximal humerus fractures. We analyzed treatment trends and performed a cost-minimization analysis comparing nonsurgical treatment, open reduction and internal fixation, reverse total shoulder arthroplasty, and hemiarthroplasty. We hypothesized that rates of surgical treatment have increased and that the costs associated with surgery are greater compared with nonsurgical management of proximal humerus fractures. METHODS: We used a US private-payer claims database of 22 million patient records from 2007 to 2016 to compare (1) cost for the episode of care from the payer perspective between each surgical group and nonsurgical treatment of proximal humerus fractures, and (2) annual trends and complication rates of each group. Cost data, including facility fees, physician fees, physical therapy, and clinic visits, were used to complete a cost-minimization analysis. RESULTS: Nonsurgical treatment was associated with lower average total costs compared with surgical intervention. Facility and physician fees accounted for most of this difference. Physical therapy costs and number of physical therapy visits were higher in each surgical group compared with nonsurgical treatment. Surgical treatment was associated with higher complications, revision rates, and length of stay. There was a small but statistically significant decrease in nonsurgical management of proximal humerus fractures between 2007 and 2016. No change was observed in rates of open reduction and internal fixation, whereas rates of reverse total shoulder arthroplasty increased and rates of hemiarthroplasty decreased. CONCLUSIONS: Nonsurgical management of proximal humerus fractures decreased during the study period. In the setting of treatment equipoise, cost-minimization analysis favors nonsurgical management of proximal humerus fractures. Surgical management is associated with higher complication rates, revision rates, and length of stay. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic Decision Analysis IV.

National Trends in the Diagnosis of CRPS after Open and Endoscopic Carpal Tunnel Release.

Background Complex regional pain syndrome (CRPS) occurs in 2 to 8% of patients that receive open or endoscopic carpal tunnel release (CTR). Because CRPS is difficult to treat after onset, identifying risk factors can inform prevention. We determined the incidence of CRPS following open and endoscopic CTR using a national claims database. We also examined whether psychosocial conditions were associated with CRPS after CTR. Methods We accessed insurance claims using diagnostic and procedural codes. We calculated the incidence of CRPS following open carpal tunnel release and endoscopic carpal tunnel release within 1 year. The response variable was the presence of CRPS after CTR. Explanatory variables included procedure type, age, gender, and preoperative diagnosis of anxiety or depression. Results The number of open CTRs (85% of total) outweighs the number of endoscopic procedures. In younger patients, the percentage of endoscopic CTRs is increasing. Rates of CRPS are nearly identical between surgery types for both privately insured (0.3%) and Medicare patients (0.1%). Middle aged (range: 40-64 years) and female patients had significantly higher rates of CRPS than did the general population. Preoperative psychosocial conditions did not correlate with the presence of CRPS in surgical patients. Clinical Relevance The decision between endoscopic and open CTR should not be made out of concern for development of CRPS postsurgery, as rates are low and similar for both procedures. Rates of CRPS found in this study are much lower than rates found in previous studies, indicating inconsistency in diagnosis and reporting or generalizability of prior work. Preoperative psychosocial disorders and CRPS are unrelated.

Rates of Perioperative Complications Among Patients Undergoing Orthopedic Trauma Surgery Despite Having Positive Results for Methamphetamine.

The burden of psychosocial problems, including substance abuse, is high among trauma patients. Use of illicit substances is often noted during urine toxicology screening on admission and can delay surgery because of concerns for an interaction with anesthesia. Methamphetamine theoretically has potential to increase perioperative anesthetic risks. However, the authors are unaware of any studies documenting increased rates of cardiovascular complications in the perioperative period among orthopedic trauma patients. This study sought to determine the rate of cardiovascular complications in these patients. The authors reviewed the medical records of all patients between 2013 and 2018 who underwent orthopedic trauma surgery at two level I trauma centers in the setting of a methamphetamine-positive urine toxicology screening prior to surgery. Information on demographics, injury, type of surgical intervention, and incidence of perioperative cardiovascular and overall medical complications prior to discharge was recorded. Ninety-four patients were included in the study (mean age, 44 years; range, 16-78 years). Twenty-six (28%) patients had multiple injuries. Thirteen (14%) patients had debridement and/or provisional stabilization of an open or unstable fracture, 18 (19%) had treatment for an infection, and 63 (67%) had definitive fracture surgery. The overall rates of perioperative cardiovascular complications and perioperative medical complications were 2.1% and 3.2%, respectively. This study provides both a baseline understanding of the complication rate for methamphetamine-positive orthopedic trauma patients during general anesthesia and justification for larger multicenter studies to further investigate this topic. [Orthopedics. 2019; 42(4):192-196.].

Microfractures and hydrogel scaffolds in the treatment of osteochondral knee defects: A clinical and histological evaluation.

BACKGROUND: Osteochondral knee defects (OCD) are often symptomatic, causing pain and functional impairment even in young and active patients. Regenerative surgical options, aiming to stimulate natural cartilage healing, have been recently used as a first line treatment. In this study, a new hydrogel is investigated in its capacity to regenerate the ultra-structural quality of hyaline cartilage when combined with a classical microfracture technique. MATERIAL AND METHODS: Forty-six patients, affected by grade III and IV knee chondropathies, were consecutively treated between 2013 and 2015 with microfractures followed by application of a modern hydrogel in the lesion site. All patients underwent clinical evaluation (WOMAC) pre-operatively, at 6,12 and at 24 months postoperatively: the results were compared with a subsequent, consecutive, matched, control group of 23 patients treated with microfractures alone. In a parallel and separate in-vitro histological study, adipose derived mesenchymal stem cells (ADMSCs) were encapsulated in the hydrogel scaffold, induced to differentiation into chondrocytes, and observed for a 3 weeks period. RESULTS: The initial WOMAC score of 58.6 ±â€¯11.0 in the study group was reduced by 88% at 6 months (7.1 ±â€¯9.2) and 95% at 24 months (2.9 ±â€¯5.9). The "in-vitro" study revealed a histological characterization typical of hyaline cartilage in study group. Separate biopsies performed at 12 months post-op in the study group also revealed type 2 collagen and hyaline-like cartilage in the regenerated tissue. CONCLUSION: Our study demonstrated high patient satisfaction rates after microfractures combined with a modern hydrogel scaffold; histologic evaluation supported the hypothesis of creating an enhanced chondrogenic environment. Microfracture "augmentation" using modern acellular biomaterials, like hydrogels, might improve the clinical outcomes of this classical bone marrow stimulating procedure.

The LOOP Estimator: Adjusting for Covariates in Randomized Experiments.

BACKGROUND: When conducting a randomized controlled trial, it is common to specify in advance the statistical analyses that will be used to analyze the data. Typically, these analyses will involve adjusting for small imbalances in baseline covariates. However, this poses a dilemma, as adjusting for too many covariates can hurt precision more than it helps, and it is often unclear which covariates are predictive of outcome prior to conducting the experiment. OBJECTIVES: This article aims to produce a covariate adjustment method that allows for automatic variable selection, so that practitioners need not commit to any specific set of covariates prior to seeing the data. RESULTS: In this article, we propose the "leave-one-out potential outcomes" estimator. We leave out each observation and then impute that observation's treatment and control potential outcomes using a prediction algorithm such as a random forest. In addition to allowing for automatic variable selection, this estimator is unbiased under the Neyman-Rubin model, generally performs at least as well as the unadjusted estimator, and the experimental randomization largely justifies the statistical assumptions made.

Identification of the First Diketomorpholine Biosynthetic Pathway Using FAC-MS Technology.

Filamentous fungi are prolific producers of secondary metabolites with drug-like properties, and their genome sequences have revealed an untapped wealth of potential therapeutic leads. To better access these secondary metabolites and characterize their biosynthetic gene clusters, we applied a new platform for screening and heterologous expression of intact gene clusters that uses fungal artificial chromosomes and metabolomic scoring (FAC-MS). We leverage FAC-MS technology to identify the biosynthetic machinery responsible for production of acu-dioxomorpholine, a metabolite produced by the fungus, Aspergilllus aculeatus. The acu-dioxomorpholine nonribosomal peptide synthetase features a new type of condensation domain (designated CR) proposed to use a noncanonical arginine active site for ester bond formation. Using stable isotope labeling and MS, we determine that a phenyllactate monomer deriving from phenylalanine is incorporated into the diketomorpholine scaffold. Acu-dioxomorpholine is highly related to orphan inhibitors of P-glycoprotein targets in multidrug-resistant cancers, and identification of the biosynthetic pathway for this compound class enables genome mining for additional derivatives.

Interrogation of Benzomalvin Biosynthesis Using Fungal Artificial Chromosomes with Metabolomic Scoring (FAC-MS): Discovery of a Benzodiazepine Synthase Activity.

The benzodiazepine benzomalvin A/D is a fungally derived specialized metabolite and inhibitor of the substance P receptor NK1, biosynthesized by a three-gene nonribosomal peptide synthetase cluster. Here, we utilize fungal artificial chromosomes with metabolomic scoring (FAC-MS) to perform molecular genetic pathway dissection and targeted metabolomics analysis to assign the in vivo role of each domain in the benzomalvin biosynthetic pathway. The use of FAC-MS identified the terminal cyclizing condensation domain as BenY-CT and the internal C-domains as BenZ-C1 and BenZ-C2. Unexpectedly, we also uncovered evidence suggesting BenY-CT or a yet to be identified protein mediates benzodiazepine formation, representing the first reported benzodiazepine synthase enzymatic activity. This work informs understanding of what defines a fungal CT domain and shows how the FAC-MS platform can be used as a tool for in vivo analyses of specialized metabolite biosynthesis and for the discovery and dissection of new enzyme activities.

Health-related quality of life outcomes from a contemporary prostate cancer registry in a large diverse population.

OBJECTIVE: To assess the health-related quality of life (HRQoL) of patients with prostate cancer up to 24 months after treatment in a contemporary large diverse population. PATIENTS AND METHODS: Patients with newly diagnosed prostate cancer from March 2011 to January 2014 in our healthcare system were included. The Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire was administered before treatment, and at 1, 3, 6, 12, 18, and 24 months after treatment up to November 2014 for all methods of treatment. The Kruskall-Wallis test was used to compare the distribution of each EPIC-26 domain score at each time point, and mixed models were used to assess the overall scores over the period after treatment. RESULTS: In all, 5 727 patients were included. There were data for 3 422, 2 329, 2 017, 1 922, 1 772, 1 260, and 837 patients before treatment, and at 1, 3, 6, 12, 18, and 24 months after treatment, respectively. At 1 month, bowel scores were the lowest for patients that had had radiation therapy, and urinary irritative symptoms were the lowest for those who had had brachytherapy. There were sexual function declines for all the treatment methods, with surgery having the steepest decline; open radical prostatectomy (ORP) had a greater decline than robot-assisted laparoscopic prostatectomy (RALP). Patients who underwent RALP had a better return of sexual function, approaching that of brachytherapy and radiation therapy at 24 months. Urinary incontinence (UI) also declined the most in surgical patients, with RALP patients improving slightly more than ORP patients at 12-24 months. CONCLUSIONS: Patients' HRQoL after prostate cancer treatment varies by treatment method. Notably, sexual function recovers most for RALP patients. UI remains worse at 24 months after surgery, compared to other methods of prostate cancer treatment.