A map of the rubisco biochemical landscape.

Rubisco is the primary CO2 fixing enzyme of the biosphere yet has slow kinetics. The roles of evolution and chemical mechanism in constraining the sequence landscape of rubisco remain debated. In order to map sequence to function, we developed a massively parallel assay for rubisco using an engineered E. coli where enzyme function is coupled to growth. By assaying >99% of single amino acid mutants across CO2 concentrations, we inferred enzyme velocity and CO2 affinity for thousands of substitutions. We identified many highly conserved positions that tolerate mutation and rare mutations that improve CO2 affinity. These data suggest that non-trivial kinetic improvements are readily accessible and provide a comprehensive sequence-to-function mapping for enzyme engineering efforts.

Protein design using structure-based residue preferences.

Recent developments in protein design rely on large neural networks with up to 100s of millions of parameters, yet it is unclear which residue dependencies are critical for determining protein function. Here, we show that amino acid preferences at individual residues-without accounting for mutation interactions-explain much and sometimes virtually all of the combinatorial mutation effects across 8 datasets (R2 ~ 78-98%). Hence, few observations (~100 times the number of mutated residues) enable accurate prediction of held-out variant effects (Pearson r > 0.80). We hypothesized that the local structural contexts around a residue could be sufficient to predict mutation preferences, and develop an unsupervised approach termed CoVES (Combinatorial Variant Effects from Structure). Our results suggest that CoVES outperforms not just model-free methods but also similarly to complex models for creating functional and diverse protein variants. CoVES offers an effective alternative to complicated models for identifying functional protein mutations.

Association Between Graft Type and Risk of Repeat Revision Anterior Cruciate Ligament Reconstruction: A Cohort Study of 1747 Patients.

BACKGROUND: With an increasing number of primary anterior cruciate ligament reconstructions (ACLRs), the burden of revision ACLR (rACLR) has also increased. Graft choice for rACLR is complicated by patient factors and the remaining available graft options. PURPOSE: To examine the association between graft type at the time of rACLR and the risk of repeat rACLR (rrACLR) in a large US integrated health care system registry while accounting for patient and surgical factors at the time of revision surgery. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Data from the Kaiser Permanente ACLR registry were used to identify patients who underwent a primary isolated ACLR between 2005 and 2020 and then went on to have rACLR. Graft type used at rACLR, classified as autograft versus allograft, was the exposure of interest. Multivariable Cox proportional hazard regression was used to evaluate the risk of rrACLR, with ipsilateral and contralateral reoperation as secondary outcomes. Models included factors at the time of the rACLR (age, sex, body mass index, smoking status, staged revision, femoral fixation, tibial fixation, femoral tunnel method, lateral meniscal injury, medial meniscal injury, and cartilage injury) and a factor from the primary ACLR (activity at injury) as covariates. RESULTS: A total of 1747 rACLR procedures were included. The crude cumulative rrACLR incidence at 8-year follow-up was 13.9% for allograft and 6.0% for autograft. Cumulative ipsilateral reoperation incidence at 8-year follow-up was 18.3% for allograft and 18.9% for autograft; contralateral reoperation cumulative incidence was 4.3% for allograft and 6.8% for autograft. With adjustment for covariates, a 70% lower risk for rrACLR was observed for autograft compared with allograft (hazard ratio [HR], 0.30; 95% CI, 0.18-0.50; P < .0001). No differences were observed for ipsilateral reoperation (HR, 1.05; 95% CI, 0.73-1.51; P = .78) or contralateral reoperation (HR, 1.33; 95% CI, 0.60-2.97; P = .48). CONCLUSION: The use of autograft at rACLR was associated with a 70% lower risk of rrACLR compared with allograft in this cohort from the Kaiser Permanente ACLR registry. When accounting for all reoperations outside of rrACLR after rACLR, the authors found no significant difference in risk between autograft and allograft. To minimize the risk of rrACLR, surgeons should consider using autograft for rACLR when possible.

Surgical Outcomes After Bucket-Handle Meniscal Repairs: Analysis of a Large Contained Cohort.

BACKGROUND: Representing approximately 10% of all meniscal tears, bucket-handle meniscal tears (BHMTs) are large longitudinal vertical tears that have an attached fragment flipped into the intercondylar notch. Meniscectomy often results in significant meniscal loss and increased joint loading. Alternatively, meniscal repair attempts to restore the function of the meniscus and aims to preserve joint mechanics. PURPOSE: To evaluate the long-term risk of subsequent ipsilateral knee surgery in patients who underwent a bucket-handle meniscal repair (BHMR), and to assess risk factors associated with subsequent knee surgical intervention. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: We performed an electronic health record search for all patients aged 12 to 65 years who underwent arthroscopic knee meniscal repairs for BHMT (2011-2018). We excluded patients who had a previous BHMR, did not have magnetic resonance imaging of the knee within 60 days before BHMR, lacked active membership in Kaiser insurance in the year before and after BHMR, or underwent meniscectomy before BHMR. All patients were followed until December 31, 2019, with censoring at death or membership disenrollment. Primary outcomes included ipsilateral knee procedures overall and by type (ie, repeat meniscal repair and meniscectomy); secondary outcomes included other surgical interventions of the same knee, any contralateral knee surgery, deep surgical-site infection, and deep venous thrombosis or pulmonary embolism. RESULTS: The final cohort included 1359 patients with a median age of 24 years (interquartile range [IQR], 17-34) who underwent BHMR for a BHMT. During the follow-up period (median, 50.2 months [IQR, 32.3-60.6]), 495 subsequent ipsilateral procedures were performed in 274 (20.2%) patients, and the median time to the first procedure was 10.6 months (IQR, 4.1-23.5). An overall 59 (4.3%) patients underwent repeat meniscal repair, and 165 (12.1%) had a subsequent meniscectomy of the same knee. Significant risk factors for subsequent ipsilateral procedures included younger age, 12 to 18 years (adjusted odds ratio [aOR], 5.77 [95% CI, 1.84-18.08]) and 19 to 30 years (aOR, 3.65 [95% CI, 1.17-11.36]), as well as normal and overweight body mass index (aOR, 2.84 [95% CI, 1.29-6.23] and 2.34 [95% CI, 1.06-5.17], respectively). Patients undergoing concomitant anterior cruciate ligament reconstruction (ACLR) at the initial BHMR had a lower risk of undergoing subsequent surgery (aOR, 0.66 [95% CI, 0.49-0.87]) than those without concomitant ACLR. CONCLUSION: This is the largest reported study on outcomes after BHMR in a contained cohort. One-fifth of patients underwent subsequent ipsilateral surgery during follow-up, with 4.3% receiving a repeat meniscal repair and 12.1% experiencing a meniscectomy. Risk factors for subsequent surgery of the same knee included younger age and normal or overweight body mass index. Concomitant ACLR at time of BHMR reduced the risk of subsequent reoperation.

Co-evolution of interacting proteins through non-contacting and non-specific mutations.

Proteins often accumulate neutral mutations that do not affect current functions but can profoundly influence future mutational possibilities and functions. Understanding such hidden potential has major implications for protein design and evolutionary forecasting but has been limited by a lack of systematic efforts to identify potentiating mutations. Here, through the comprehensive analysis of a bacterial toxin-antitoxin system, we identified all possible single substitutions in the toxin that enable it to tolerate otherwise interface-disrupting mutations in its antitoxin. Strikingly, the majority of enabling mutations in the toxin do not contact and promote tolerance non-specifically to many different antitoxin mutations, despite covariation in homologues occurring primarily between specific pairs of contacting residues across the interface. In addition, the enabling mutations we identified expand future mutational paths that both maintain old toxin-antitoxin interactions and form new ones. These non-specific mutations are missed by widely used covariation and machine learning methods. Identifying such enabling mutations will be critical for ensuring continued binding of therapeutically relevant proteins, such as antibodies, aimed at evolving targets.

Acute and subacute anterior cruciate ligament reconstructions are associated with a higher risk of revision and reoperation.

PURPOSE: (1) Report concomitant cartilage and meniscal injury at the time of anterior cruciate ligament reconstruction (ACLR), (2) evaluate the risk of aseptic revision ACLR during follow-up, and (3) evaluate the risk of aseptic ipsilateral reoperation during follow-up. METHODS: Using a United States integrated healthcare system's ACLR registry, patients who underwent primary isolated ACLR were identified (2010-2018). Multivariable Cox proportional-hazards regression was used to evaluate the risk of aseptic revision, with a secondary outcome evaluating ipsilateral aseptic reoperation. Outcomes were evaluated by time from injury to ACLR: acute (< 3 weeks), subacute (3 weeks-3 months), delayed (3-9 months), and chronic (≥ 9 months). RESULTS: The final sample included 270 acute (< 3 weeks), 5971 subacute (3 weeks-3 months), 5959 delayed (3-9 months), and 3595 chronic (≥ 9 months) ACLR. Medial meniscus [55.4% (1990/3595 chronic) vs 38.9% (105/270 acute)] and chondral injuries [40.0% (1437/3595 chronic) vs 24.8% (67/270 acute)] at the time of ACLR were more common in the chronic versus acute groups. The crude 6-year revision rate was 12.9% for acute ACLR, 7.0% for subacute, 5.1% for delayed, and 4.4% for chronic ACLR; reoperation rates a 6-year follow-up was 15.0% for acute ACLR, 9.6% for subacute, 6.4% for delayed, and 8.1% for chronic ACLR. After adjustment for covariates, acute and subacute ACLR had higher risks for aseptic revision (acute HR 1.70, 95% CI 1.07-2.72, p = 0.026; subacute HR 1.25, 95% CI 1.01-1.55, p = 0.040) and aseptic reoperation (acute HR 2.04, 95% CI 1.43-2.91, p < 0.001; subacute HR 1.31, 95% CI 1.11-1.54, p = 0.002) when compared to chronic ACLR. CONCLUSIONS: In this cohort study, while more meniscal and chondral injuries were reported for ACLR performed ≥ 9 months after the date of injury, a lower risk of revision and reoperation was observed following chronic ACLR relative to patients undergoing surgery in acute or subacute fashions.

Comparison of Anterior Cruciate Ligament Tears Treated Nonoperatively Versus With Reconstruction: Risk of Subsequent Surgery.

BACKGROUND: Anterior cruciate ligament (ACL) tears can be devastating injuries, leading to joint instability, meniscal tears, and subsequent arthritis. It is unknown whether ACL reconstruction (ACLR) alters the natural history of joint degeneration in the ACL-deficient knee compared with nonoperative treatment, and few studies have examined outcomes in middle-aged patients. PURPOSE: The objective of this study was to compare the midterm risk of subsequent ipsilateral knee surgery in middle-aged patients after an ACL injury treated with initial conservative (nonoperative) management (CM) versus ACLR (operative management [OM]) within 6 months of the diagnosis. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We performed an electronic database search from 2011 to 2012 for all patients aged 35 to 55 years with an initial diagnosis of magnetic resonance imaging-confirmed ACL tear. Patients who elected CM and those who underwent ACLR within 6 months of the diagnosis (OM) were identified. Index patient and clinical characteristics were collected from the health record. All patients were longitudinally observed until August 31, 2017. The primary outcome was subsequent ipsilateral knee surgeries, and secondary outcomes included contralateral knee surgeries, deep surgical-site infections, and venous thrombotic events. RESULTS: The mean follow-up was 4.8 ± 0.6 years. The CM group included 463 patients (40.2%) and the OM group included 690 patients (59.8%). The mean ages were 43.9 ± 5.7 years and 42.7 ± 5.3 years for patients in the CM and OM groups, respectively (P < .001). Obesity and smoking were significantly more common in the CM group. During the follow-up, 180 patients (38.9%) in the CM group underwent subsequent ipsilateral knee surgery compared with 73 (10.6%) patients in the OM group (P < .001). The mean time to the first ipsilateral procedure was 0.9 ± 1.1 years in the CM and 2 ± 1.5 years in the OM group (P < .001). Delayed ipsilateral ACLRs were performed in 81 patients in the CM group (17.5%); non-ACLR ipsilateral knee surgeries were performed in 156 patients in the CM group (33.7%). Contralateral knee surgery rates were similar. In a regression model, after controlling for age, sex, the Charlson Comorbidity Index score, and smoking status, it was found that normal body mass index and CM group were risk factors for undergoing subsequent knee surgery or ipsilateral non-ACLR surgery. CONCLUSION: Excluding delayed ACLR, subsequent ipsilateral knee surgeries were more common and occurred earlier in middle-aged patients with nonoperatively managed ACL tears compared with patients managed with reconstruction.

Risk Factors for Conversion of Hip Arthroscopy to Total Hip Arthroplasty: A Large Closed-Cohort Study.

PURPOSE: To evaluate risk factors for conversion of hip arthroscopy to total hip arthroplasty (THA) within 2 years in a closed patient cohort. METHODS: This study was a case series of consecutive hip arthroscopy procedures from September 2008 to November 2018 in the electronic medical record of Kaiser Permanente Northern California. Patients were included with minimum 2-year follow-up or if they had conversion to THA within 2 years (the primary outcome) regardless of follow-up time. Patient characteristics at the time of the index arthroscopy were extracted; characteristics of patients who experienced the outcome event versus those who did not were compared by use of multivariable logistic regression models and receiver operating characteristic (ROC) curves. RESULTS: The mean follow-up time was 4.9 years (median 4.6, range 0.6 to 11.6). The mean age was 37.2 years (range 10 to 88), and 57% were female. During the follow-up period, 82 patients underwent a THA within 2 years of their arthroscopies (5.3%, 95% confidence interval 4.3% to 6.5%) after a median time of 9 months (interquartile range 5.9 to 14.4) after the initial arthroscopy. Increasing age was highly predictive of early THA conversion (area under the ROC curve = 0.78, P < .001). Although other predictors showed significant bivariable associations with early failure, body mass index (BMI), race, sex, and prior arthroscopy did not add meaningful independent predictive information. CONCLUSIONS: The risk of conversion to THA within 2 years after hip arthroscopy increased substantially with patient age at the time of the procedure. BMI, race, sex, and prior arthroscopy were not important independent predictors of conversion beyond the information contained in patient age. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Evaluation of Durability of Transparent Graphene Electrodes Fabricated on Different Flexible Substrates for Chronic In Vivo Experiments.

OBJECTIVE: To investigate chronic durability of transparent graphene electrodes fabricated on polyethylene terephthalate (PET) and SU-8 substrates for chronic in vivo studies. METHODS: We perform systematic accelerated aging tests to understand the chronic reliability and failure modes of transparent graphene microelectrode arrays built on PET and SU-8 substrates. We employ graphene microelectrodes fabricated on PET substrate in chronic in vivo experiments with transgenic mice. RESULTS: Our results show that graphene microelectrodes fabricated on PET substrate work reliably after 30 days accelerated aging test performed at 87 °C, equivalent to 960 days in vivo lifetime. We demonstrate stable chronic recordings of cortical potentials in multimodal imaging/recording experiments using transparent graphene microelectrodes fabricated on PET substrate. On the other hand, graphene microelectrode arrays built on SU-8 substrate exhibit extensive crack formation across microelectrode sites and wires after one to two weeks, resulting in total failure of recording capability for chronic studies. CONCLUSION: PET shows superior reliability as a substrate for graphene microelectrode arrays for chronic in vivo experiments. SIGNIFICANCE: Graphene is a unique neural interface material enabling cross-talk free integration of electrical and optical recording and stimulation techniques in the same experiment. To date, graphene-based microelectrode arrays have been demonstrated in various multi-modal acute experiments involving electrophysiological sensing or stimulation, optical imaging and optogenetics stimulation. Understanding chronic reliability of graphene-based transparent interfaces is very important to expand the use of this technology for long-term behavioral studies with animal models.

Revision Risk of Soft Tissue Allograft Versus Hybrid Graft After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: When a harvested hamstring autograft is deemed by the surgeon to be of inadequate diameter, the options include using the small graft, using another autograft from a different site, augmenting with an allograft (hybrid graft), using a different configuration of the graft (eg, 5- or 6-stranded), or abandoning the autograft and using allograft alone. A small graft diameter is associated with a higher revision risk, and using another autograft site includes added harvest-site morbidity; therefore, use of a hybrid graft or an allograft alone may be appealing alternative options. Revision risk for hybrid graft compared with soft tissue allograft is not known. PURPOSE: To evaluate the risk for aseptic revision surgery after primary anterior cruciate ligament reconstruction (ACLR) using a soft tissue allograft compared with ACLR using a hybrid graft in patients 25 years and younger. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Data from a health care system's ACLR registry were used to identify primary isolated unilateral ACLRs between 2009 and 2016 using either a hybrid graft (hamstring autograft with soft tissue allograft) or a soft tissue allograft alone. Multivariable Cox proportional hazards regression was used to evaluate risk for aseptic revision after ACLR according to graft used after adjustment for age, allograft processing, tunnel drilling technique, and region where the primary ACLR was performed. RESULTS: The cohort included 2080 ACLR procedures; a hybrid graft was used for 479 (23.0%) ACLRs. Median follow-up time was 3.4 years (interquartile range, 1.8-5.1 years). The crude 2-year aseptic revision probability was 5.4% (95% CI, 4.3%-6.7%) for soft tissue allograft ACLR and 3.8% (95% CI, 2.3%-6.4%) for hybrid graft ACLR. After adjustment for covariates, soft tissue allograft ACLR had a higher risk of aseptic revision during follow-up compared with hybrid graft ACLR (hazard ratio, 2.00; 95% CI, 1.21-3.31; P = .007). CONCLUSION: Soft tissue allografts had a 2-fold higher risk of aseptic revision compared with hybrid graft after ACLR. Future studies evaluating the indications for using hybrid grafts and the optimal hybrid graft diameter is needed.

Tibial Tubercle Osteotomy and Medial Patellofemoral Ligament Imbrication for Patellar Instability Due to Trochlear Dysplasia.

BACKGROUND: The treatment of patellar instability in the setting of trochlear dysplasia is challenging. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate outcomes for the treatment of recurrent patellar dislocations due to trochlear dysplasia using anteromedialization tibial tubercle osteotomy combined with medial patellofemoral ligament (MPFL) imbrication. We hypothesized that the treatment of patellar instability with tibial tubercle osteotomy and MPFL imbrication would result in improved patient satisfaction and decrease patellar instability events in patients with prior instability and trochlear dysplasia. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: We performed a retrospective analysis of patients who underwent MPFL imbrication and concomitant anteromedialization tibial tubercle osteotomy for recurrent patellofemoral instability at a single institution. The minimum follow-up was 1 year. Patient demographic information including age at the time of surgery, sex, body mass index (BMI), tibial tubercle-trochlear groove (TT-TG) distance, and grade of trochlear dysplasia was collected along with relevant operative data. Postoperatively, recurrent dislocation events as well as Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index, and Kujala scores were collected, and satisfaction was ascertained by asking patients whether they would undergo the procedure again. RESULTS: A total of 37 knees from 31 patients (23 female) with a mean follow-up of 3.8 years (range, 1-8.9 years) were included. The mean patient age was 28.8 years (range, 14-45 years), the mean BMI was 24 kg/m2 (range, 20-38 kg/m2), and the mean preoperative TT-TG distance was 18.9 mm (range, 8.4-32.4 mm). Two knees were classified as low-grade trochlear dysplasia (Dejour A) and 35 as high-grade trochlear dysplasia (Dejour B-D). At final follow-up, patients reported mean KOOS subscale scores of 86.5 (Pain), 79.8 (Symptoms), 93.9 (Activities of Daily Living), 74.3 (Sports/Recreation), and 61.9 (Quality of Life), as well as a mean Kujala score of 81.3. Mean patient satisfaction was 8.3 of 10. The majority of knees (86.5%; 32/37) remained stable without recurrent instability after this procedure, while 13.5% (5 knees) suffered a recurrent dislocation, with 2 requiring revision surgery. Eight knees (21.6%) underwent subsequent hardware removal. CONCLUSION: Anteromedialization tibial tubercle osteotomy with MPFL imbrication can improve recurrent patellofemoral instability and provide significant clinical benefit to patients with trochlear dysplasia.

Author Correction: Affinity-based capture and identification of protein effectors of the growth regulator ppGpp.

In the version of the article originally published, two sets of labels on the x axis of the graph in Fig. 5b were in reverse order. In the 'PurF' row, the locations of 'N48A' and 'R45A' should be switched, and in the row below those of '4.1' and the minus sign should be switched. Shown below are the original and corrected versions of Fig. 5b. The error has been corrected in the HTML and PDF versions of the article.

Affinity-based capture and identification of protein effectors of the growth regulator ppGpp.

The nucleotide ppGpp is a highly conserved regulatory molecule in bacteria that helps tune growth rate to nutrient availability. Despite decades of study, how ppGpp regulates growth remains poorly understood. Here, we developed and validated a capture-compound mass spectrometry approach that identified >50 putative ppGpp targets in Escherichia coli. These targets control many key cellular processes and include 13 enzymes required for nucleotide synthesis. We demonstrated that ppGpp inhibits the de novo synthesis of all purine nucleotides by directly targeting the enzyme PurF. By solving a structure of PurF bound to ppGpp, we designed a mutation that ablates ppGpp-based regulation, leading to dysregulation of purine-nucleotide synthesis following ppGpp accumulation. Collectively, our results provide new insights into ppGpp-based growth control and a nearly comprehensive set of targets for future exploration. The capture compounds developed should also enable the rapid identification of ppGpp targets in any species, including pathogens.

Continuous Infraclavicular Brachial Block Versus Single-Shot Nerve Block for Distal Radius Surgery: A Prospective Randomized Control Trial.

OBJECTIVES: To compare the efficacy of an infraclavicular single-shot nerve block to a continuous infusion through an OnQ infusion pump for rebound pain (between 12 and 24 hours postoperatively) and postoperative narcotic analgesia requirements in distal radius fractures. DESIGN: Prospective randomized control trial. SETTINGS: Performed at 2 hospitals affiliated with a large urban academic medical center. PATIENTS: Fifty patients undergoing operative fixation of distal radius fractures (OTA/AO type 23B/C). INTERVENTION: Patients were randomized to receive either an infraclavicular block as a single shot (SSB group) or a continuous infusion through an OnQ pump (OnQ group). MAIN OUTCOME MEASURES: Visual analog scale (0-10) pain levels and amount of pain medication taken. RESULTS: At all time points after discharge, mean postoperative pain scores were lower in the OnQ group versus the SSB group but did not reach statistical significance. At 12 hours postoperatively, the SSB group and OnQ group pain scores, respectively, were 5.2 and 4.1 (P = 0.1615). At 24 hours, the pain scores for the SSB and OnQ group, respectively, were 5.4 and 4.8 (P = 0.1918). At these same time points, the Percocet taken were the same at 1.3 and 2.3 (P = 0.8328 and 0.8617). Overall 5 of 24 patients in the OnQ group had pump malfunctions with 4 being removed before 48 hours. CONCLUSION: OnQ pump is not associated with statistically improved postoperative pain control compared with a single nerve block for distal radius fractures and did not address rebound pain. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

The effect of patient gender on outcomes after reverse total shoulder arthroplasty.

BACKGROUND: Gender differences may exist for patients undergoing shoulder arthroplasty. Limited data suggest that women may have worse preoperative disability and outcomes. Our objective was to determine whether gender influences preoperative disability and patient-reported outcomes after reverse total shoulder arthroplasty. METHODS: Data were prospectively collected for patients who underwent reverse total shoulder arthroplasty for rotator cuff arthropathy or osteoarthritis with a rotator cuff tear at a single institution between 2009 and 2015. Range of motion, visual analog scale, 12-Item Short Form Health Survey (SF-12), and American Shoulder and Elbow Surgeons (ASES) scores were collected at the preoperative, 1-year, and 2-year postoperative time points. Data were analyzed using multivariate mixed-effect regression analysis. RESULTS: There were 117 patients included. Men and women had similar demographics, preoperative range of motion, pain, and function. Length of stay was similar (men, 2.32 days; women, 2.58 days; P = .18). Controlling for patient variables, men achieved higher ASES function (P = .009) and SF-12 Physical Component Summary (P = .008) scores compared with women. There was no difference between men and women in ASES pain and SF-12 Mental Component Summary scores, visual analog scale score, or range of motion. CONCLUSION: Improvements in pain and range of motion were similar in men and women; however, men achieved higher ASES function and SF-12 Physical Component Summary scores. Women may be more functionally impaired on the basis of differences in activities of daily living. These results may be used to guide discussion about expected benefits after reverse shoulder arthroplasty.

Comparison of general versus isolated regional anesthesia in total shoulder arthroplasty: A retrospective propensity-matched cohort analysis.

BACKGROUND: Intraoperative anesthetic typically consists of either general anesthesia (GA) or isolated regional anesthesia (RA). METHODS: A retrospective propensity-matched cohort analysis on patients undergoing TSA was performed to determine differences between GA and RA in regard to patient population, complications, LOS and hospital readmission. RESULTS: 4158 patients underwent TSA with GA or isolated RA. Propensity-matching resulted in 912 patients in each cohort. RA had lower overall in-hospital complications and greater homebound discharge disposition with lower 90-day readmission rates than GA. CONCLUSION: After TSA, isolated RA was associated with lower in-hospital complications, readmission rates and odds of hospital readmission than GA.

Subsequent Surgery After Revision Anterior Cruciate Ligament Reconstruction: Rates and Risk Factors From a Multicenter Cohort.

BACKGROUND: While revision anterior cruciate ligament reconstruction (ACLR) can be performed to restore knee stability and improve patient activity levels, outcomes after this surgery are reported to be inferior to those after primary ACLR. Further reoperations after revision ACLR can have an even more profound effect on patient satisfaction and outcomes. However, there is a current lack of information regarding the rate and risk factors for subsequent surgery after revision ACLR. PURPOSE: To report the rate of reoperations, procedures performed, and risk factors for a reoperation 2 years after revision ACLR. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total of 1205 patients who underwent revision ACLR were enrolled in the Multicenter ACL Revision Study (MARS) between 2006 and 2011, composing the prospective cohort. Two-year questionnaire follow-up was obtained for 989 patients (82%), while telephone follow-up was obtained for 1112 patients (92%). If a patient reported having undergone subsequent surgery, operative reports detailing the subsequent procedure(s) were obtained and categorized. Multivariate regression analysis was performed to determine independent risk factors for a reoperation. RESULTS: Of the 1112 patients included in the analysis, 122 patients (11%) underwent a total of 172 subsequent procedures on the ipsilateral knee at 2-year follow-up. Of the reoperations, 27% were meniscal procedures (69% meniscectomy, 26% repair), 19% were subsequent revision ACLR, 17% were cartilage procedures (61% chondroplasty, 17% microfracture, 13% mosaicplasty), 11% were hardware removal, and 9% were procedures for arthrofibrosis. Multivariate analysis revealed that patients aged <20 years had twice the odds of patients aged 20 to 29 years to undergo a reoperation. The use of an allograft at the time of revision ACLR (odds ratio [OR], 1.79; P = .007) was a significant predictor for reoperations at 2 years, while staged revision (bone grafting of tunnels before revision ACLR) (OR, 1.93; P = .052) did not reach significance. Patients with grade 4 cartilage damage seen during revision ACLR were 78% less likely to undergo subsequent operations within 2 years. Sex, body mass index, smoking history, Marx activity score, technique for femoral tunnel placement, and meniscal tearing or meniscal treatment at the time of revision ACLR showed no significant effect on the reoperation rate. CONCLUSION: There was a significant reoperation rate after revision ACLR at 2 years (11%), with meniscal procedures most commonly involved. Independent risk factors for subsequent surgery on the ipsilateral knee included age <20 years and the use of allograft tissue at the time of revision ACLR.

Congenital Pseudoarthrosis of the Distal Radius Treated With Physeal-Sparing Double-Barrel Vascularized Free Fibula Transfer: A Case Report.

BACKGROUND: Neurofibromatosis type 1 is a hereditary disease that can lead to pseudoarthrosis of various long bones. Rarely, pseudoarthrosis affects the forearm, and to the best of our knowledge, this is the first reported case of pseudarthrosis of the distal radius treated by this unique method. METHODS: We present a case of a 7-year-old male who underwent multiple operations to treat pseudoarthrosis of the distal radius. RESULTS: After failed conservative and operative fixation augmented with autologous iliac crest bone grafting, the patient underwent a successful double-barrel vascularized free fibula graft while preserving the physis of the distal radius. CONCLUSION: Double-barrel vascularized free fibula bone graft can be successfully used as the definitive treatment in refractory cases of distal forearm pseudarthrosis and we believe that our technique can be applied to all cases of pseudarthrosis in other patients with a similar presentation and lesion location.

cis-Acting Complex-Trait-Associated lincRNA Expression Correlates with Modulation of Chromosomal Architecture.

Intergenic long noncoding RNAs (lincRNAs) are the largest class of transcripts in the human genome. Although many have recently been linked to complex human traits, the underlying mechanisms for most of these transcripts remain undetermined. We investigated the regulatory roles of a high-confidence and reproducible set of 69 trait-relevant lincRNAs (TR-lincRNAs) in human lymphoblastoid cells whose biological relevance is supported by their evolutionary conservation during recent human history and genetic interactions with other trait-associated loci. Their enrichment in enhancer-like chromatin signatures, interactions with nearby trait-relevant protein-coding loci, and preferential location at topologically associated domain (TAD) boundaries provide evidence that TR-lincRNAs likely regulate proximal trait-relevant gene expression in cis by modulating local chromosomal architecture. This is consistent with the positive and significant correlation found between TR-lincRNA abundance and intra-TAD DNA-DNA contacts. Our results provide insights into the molecular mode of action by which TR-lincRNAs contribute to complex human traits.

The Arthroscopic Latarjet A Bony Solution for a Bony Injury.

Treatment of shoulder instability has greatly evolved over the past century. Open capsulolabral repairs and bony augmentation procedures have slowly been replaced with arthroscopy. As arthroscopy and arthroscopic instruments have improved, surgeons have gravitated toward more minimally invasive procedures. The open Latarjet procedure has been historically very successful in preventing recurrent shoulder dislocation. While there is a steep learning curve, the arthroscopic Latarjet procedure as developed by Lafosse in 2007 can be effective in preventing shoulder instability in patients with significant bone loss of up to 30%.