Atroposelective Synthesis of Axially Chiral Naphthylpyrroles by a Catalytic Asymmetric 1,3-Dipolar Cycloaddition/Aromatization Sequence.

A straightforward methodology for the enantioselective preparation of axially chiral 2-naphthylpyrroles has been developed. This protocol is based on a CuI/Fesulphos-catalyzed highly enantioselective 1,3-dipolar cycloaddition of an azomethine ylide followed by pyrrolidine alkylation and pyrrolidine to pyrrole oxidation. The mild conditions employed in the DDQ/blue light-mediated aromatization process facilitate an effective central-to-axial chirality transfer affording the corresponding pyrroles with high atroposelectivity.

The "N+10 Rule" to Avoid Graft-Tunnel Mismatch in Bone-Patellar Tendon-Bone ACL Reconstruction Using Independent Femoral Tunnel Drilling.

Background: Graft-tunnel mismatch (GTM) is a common problem in anterior cruciate ligament (ACL) reconstruction (ACLR) using bone-patellar tendon-bone (BPTB) grafts. Hypothesis: Application of the "N+10 rule" in endoscopic ACLR with BPTB grafts will result in acceptable tibial tunnel length (TTL), minimizing GTM. Study Design: Controlled laboratory study. Methods: Endoscopic BPTB ACLR was conducted on the paired knees of 10 cadaveric specimens using 2 independent femoral tunnel drilling techniques-accessory anteromedial portal and flexible reamer. The graft bone blocks were trimmed to 10 × 20 mm, and the intertendinous distance (represented by "N") between the bone blocks was measured. The N+10 rule was used to set the angle of the ACL tibial tunnel guide to the appropriate number of degrees for drilling. The amount of excursion or recession of the tibial bone plug in relation to the anterior tibial cortical aperture was measured in both flexion and extension. A GTM threshold of ±7.5 mm was set based on prior studies. Results: The mean BPTB ACL intertendinous distance was 47.5 ± 5.5 mm. The mean measured intra-articular distance was 27.2 ± 3 mm. Using the N+10 rule, the mean total (flexion plus extension) GTM was 4.3 ± 3.2 mm (GTM in flexion, 4.9 ± 3.6 mm; GTM in extension, 3.8 ± 3.5 mm). In 18 of 20 (90%) cadaveric knees, the mean total GTM fell within the ±7.5-mm threshold. When comparing the actual measured TTL to the calculated TTL, there was a mean difference of 5.4 ± 3.9 mm. When comparing femoral tunnel drilling techniques, the total GTM for the accessory anteromedial portal technique was 2.1 ± 3.7 mm, while the total GTM for the flexible reamer technique was 3.6 ± 5.4 mm (P = .5). Conclusion: The N+10 rule resulted in an acceptable mean GTM in both flexion and extension. The mean difference between the measured versus calculated TTL using the N+10 rule was also acceptable. Clinical Relevance: The N+10 rule is a simple and effective intraoperative strategy for achieving desired TTL regardless of patient-specific factors to avoid excessive GTM in endoscopic BPTB ACLR using independent femoral tunnel drilling.

Lateral Extra-Articular Tenodesis Staple Risks Penetration of Anterior Cruciate Ligament Reconstruction Tunnel.

Purpose: To identify the risk of anterior cruciate ligament (ACL) femoral tunnel penetration with the use of a staple for lateral extra-articular tenodesis (LET) graft fixation and to determine whether this varied between 2 different techniques for ACL femoral tunnel drilling. Methods: Twenty paired, fresh-frozen, cadaver knees underwent ACL reconstruction with a LET. Left and right knees were randomized to ACL reconstruction with femoral tunnel creation by use of either a rigid guide pin and reamer through the accessory anteromedial portal or by the use of a flexible guide pin and reamer through the anteromedial portal. Immediately after tunnel creation, the LET was performed and fixated with a small Richard's staple. Fluoroscopy was used to obtain a lateral view of the knee to determine staple position, and visualization of the ACL femoral tunnel was performed with the arthroscope to investigate penetration of the staple into the femoral tunnel. The Fisher exact test was conducted to determine whether there was any difference in tunnel penetration between tunnel creation techniques. Results: The staple was noted to penetrate the ACL femoral tunnel in 8 of 20 (40%) extremities. When stratified by tunnel creation technique, the Richards staple violated 5 of 10 (50%) of the tunnels made via the rigid reaming technique compared with 3 of 10 (30%) of those created with a flexible guide pin and reamer (P = .65). Conclusions: A high incidence of femoral tunnel violation is seen with lateral extra-articular tenodesis staple fixation. Level of Evidence: Level IV, controlled laboratory study. Clinical Relevance: The risk of penetrating the ACL femoral tunnel with a staple for LET graft fixation is not well understood. Yet, the integrity of the femoral tunnel is important for the success of ACL reconstruction. Surgeons can use the information in this study to consider adjustments to operative technique, sequence, or fixation devices used when performing ACL reconstruction with concomitant LET to avoid the potential for disruption of ACL graft fixation.

Failed and Revision Rotator Cuff Repair.

With an increasing incidence of rotator cuff repairs (RCRs), and by extension, RCR failures, surgeons must be facile in the diagnosis and management of this complication. A detailed history and physical exam as well as familiarity with the patient-specific, anatomic, and technical variables that increase a patient's risk of RCR failure is critical. Modifiable factors should be addressed prior to revision RCR and non-modifiable factors should be examined as they may disqualify an individual from a revision attempt. A methodical surgical approach is critical. In general, outcomes following revision RCR are typically favorable although inferior than those following primary RCR.

Varus collapse following anterior closing wedge proximal tibial osteotomy for ACL revision reconstruction: a case series.

A slope-correcting anterior closing wedge proximal tibial osteotomy is a powerful tool for correcting increased posterior tibial slope in the setting of a failed anterior cruciate ligament reconstruction. This case series documents three cases in which patients collapsed into varus following an anterior closing wedge proximal tibia osteotomy. Two patients had osteotomies fixated with a "suture-staple" construct, and all had medical comorbidities or reported noncompliance post-operatively. Therefore, meticulous care during the planning, execution, and rehabilitation phases is critical as multiple factors throughout the arc of care may contribute towards anterior closing wedge proximal tibial osteotomy varus collapse. Careful optimization of medical comorbidities and rigid fixation with either a plate and screws or compression staples should be used rather than a "suture-staple" to mitigate this risk.Level of evidence: IV.

A Prospective, Randomized, Controlled Comparison of Adhesive Wound Closure Devices in an Orthopaedic Patient.

INTRODUCTION: The objective of this study was to compare Zip and Clozex with a typical closure using a running 3-0 Prolene suture. METHODS: A prospective, randomized, controlled trial was conducted in patients aged 18 years and older undergoing elective orthopaedic surgical procedures between 2019 and 2021. Patients were randomized to undergo skin closure using a running 3-0 Prolene suture, Zip, or Clozex. The length and location of incision, time to close, surgeon satisfaction, and complications were recorded. The Stony Brook Scar Evaluation Scale (SBSES) was used to assess cosmesis at 2 weeks and 3 months postoperatively. Patient satisfaction and adverse events were also recorded. RESULTS: Thirty-two patients were included in the analysis. Suture closure time was longer than Zip (266 vs 123 seconds; P = 0.02) and Clozex (266 vs 91 seconds; P = 0.005). SBSES scores were greater for Clozex at 2 weeks compared with suture (4.09 vs 2.8; P = 0.005). At 3 months, Clozex maintained greater scores compared with suture (3.82 vs 2.85; P = 0.023) and Zip (3.82 vs 3.0; P = 0.046).No differences were observed in patient satisfaction at any time points. DISCUSSION: Although patient satisfaction was similar across groups, wound closure times, SBSES scores, and total cost favor Clozex compared with Prolene suture or Zip. CLINICALTRIALSGOV REGISTRATION NUMBER: NCT05251064.

Interobserver Reliability and Change in the Sagittal Tibial Tubercle-Trochlear Groove Distance with Increasing Knee Flexion Angles.

The tibial tubercle-trochlear groove (TT-TG) distance is currently utilized to evaluate knee alignment in patients with patellar instability. Sagittal plane pathology measured by the sagittal tibial tubercle-trochlear groove (sTT-TG) distance has been described in instability but may also be important to consider in patients with cartilage injury. This study aims to (1) describe interobserver reliability of the sTT-TG distance and (2) characterize the change in the sTT-TG distance with respect to changing knee flexion angles. In this cadaveric study, six nonpaired cadaveric knees underwent magnetic resonance imaging (MRI) studies at each of the following degrees of knee flexion: -5, 0, 5, 10, 15, and 20. The sTT-TG distance was measured on the axial T2 sequence. Four reviewers measured this distance for each cadaver at each flexion angle. Intraclass correlation coefficients were calculated to determine interobserver reliability and reproducibility of the sTT-TG measurement. Analysis of variance (ANOVA) tests and Friedman's tests with a Bonferroni's correction were performed for each cadaver to compare sTT-TG distances at each flexion angle. Significance was defined as p < 0.05. There was excellent interobserver reliability of the sTT-TG distance with all intraclass correlation coefficients >0.9. The tibial tubercle progressively becomes more posterior in relation to the trochlear groove (more negative sTT-TG distance) with increasing knee flexion. The sTT-TG distance is a measurement that is reliable between attending surgeons and across training levels. The sTT-TG distance is affected by small changes in knee flexion angle. Awareness of knee flexion angle on MRI is important when this measurement is utilized by surgeons.

A Risk Stratification Nomogram to Predict Inpatient Admissions After Total Shoulder Arthroplasty Among Patients Eligible for Medicare.

The goal of this study was to establish a risk stratification nomogram to aid in determining the need for inpatient admission among patients who were eligible for Medicare and were undergoing primary total shoulder arthroplasty (TSA). The American College of Surgeons National Surgical Quality Improvement Program database was queried to identify all patients older than 65 years who underwent primary TSA between 2006 and 2016. The primary outcome measure was inpatient admission, as defined by hospital length of stay longer than 2 days. Multiple demographic, comorbid, and peri-operative variables were used in a multivariate logistic regression model to yield a risk stratification nomogram. A total of 1514 inpatient and 6020 out-patient admissions were analyzed. Age older than 80 years (odds ratio [OR], 2.69; P<.0001; 95% CI, 2.21-3.27), female sex (OR, 2.18; P<.0001; 95% CI, 1.90-2.51), dependent functional status (OR, 1.69; P<.0001; 95% CI, 1.2-2.38), dialysis (OR, 3.48; P=.029; 95% CI, 1.14-10.63), admission from an inpatient facility (OR, 1.76; P<.0001; 95% CI, 1.70-1.82), and inflammatory arthritis (OR, 1.69; P<.02; 95% CI, 1.25-13.78) were the greatest determinants of inpatient stay. The resulting predictive model showed acceptable discrimination and calibration. Our model enabled reliable and straightforward identification of the most suitable candidates for inpatient admission among patients who were eligible for Medicare and were undergoing primary TSA. Patients who were receiving dialysis, who had dyspnea at rest, and who had bleeding disorders were more likely to be admitted as inpatients after TSA. Larger multicenter studies are necessary to externally validate the proposed predictive nomogram. [Orthopedics. 2022;45(1):43-49.].

Discharge Destination After Shoulder Arthroplasty: An Analysis of Discharge Outcomes, Placement Risk Factors, and Recent Trends.

INTRODUCTION: Rates of shoulder arthroplasty continue to increase. Factors influencing disposition and the effect discharge destination may have on perioperative outcomes are currently unknown. This study (1) investigates patients undergoing total shoulder arthroplasty subsequently discharged to home, skilled nursing facilities, and or independent rehabilitation facilities; (2) identifies differences in perioperative outcomes; and (3) investigates the risk of adverse events and readmission after nonhome disposition. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for patients undergoing total shoulder arthroplasty from 2013 to 2018. Bivariate and multivariate analyses were conducted to determine the relationship between patient characteristics and risks of discharge to a non-home destination, discharge to an independent rehabilitation facility as opposed to a skilled nursing facility, severe postdischarge adverse events, and unplanned readmission. RESULTS: Factors associated with discharge to a non-home facility included those older than 85 years of age (odds ratio [OR], 14.38), dialysis requirement (OR, 4.16), transfer from a non-home facility (OR, 3.69), dependent functional status (OR, 3.17), female sex (OR, 2.78), history of congestive heart failure (2.05), American Society of Anesthesiologists class >2 (OR, 1.97), longer length of stay (OR, 1.47), and body mass index >35 (OR, 1.29) (P < 0.05). Patients discharged to a non-home facility had an approximately quadrupled rate of both major adverse events (8.6% vs 2.4%, P < 0.001) and minor adverse events (6.1% vs 1.4%, P < 0.001). Discharge to a non-home facility had a higher likelihood of a severe adverse event (OR, 1.82, P = 0.029) or unplanned readmission (OR, 1.60, P = 0.001). CONCLUSIONS: Non-home discharge destination demonstrated a notable negative impact on postoperative outcomes independent of medical complexity. Preoperative management of modifiable risk factors may decrease length of inpatient stay, rates of disposition to non-home facilities, and total cost of care. The benefit of more intense postoperative management at a non-home discharge destination must be carefully weighed against the independent risk of postoperative adverse events and readmissions.

Arthroscopically Assisted Acromioclavicular Joint Reconstruction Using the Infinity-Lock Button System With Allograft Augmentation.

Acromioclavicular (AC) joint injuries are extremely common in the athletic population. Although most low-grade injuries can be managed nonoperatively, high-grade injuries often require reconstruction of the AC joint. Various reconstructive options have been described with varying risks and benefits to each. Implant or graft failure with loss of reduction as well as clavicle and coracoid fracture are a few of the more common complications following AC joint reconstruction surgery. Currently, no gold standard exists. This technical paper describes an arthroscopically assisted AC joint reconstruction technique using the Infinity-Lock Button System with hamstring allograft augmentation. This technique provides an anatomic, minimally invasive, low-profile reconstruction that may minimize risk of clavicle and coracoid fracture. It also provides augmented stabilization across the AC joint, which may also help resist naturally occurring horizontal and rotational displacing forces.

Arthroscopically Assisted Acute Acromioclavicular Joint Reconstruction Using the Infinity-Lock Button System.

Acromioclavicular (AC) joint injuries are the most common shoulder injuries in the athletic population. The literature is rife with various surgical techniques and implants as well as opinion on proper timing of surgical options. Patient outcomes are generally similar across fixation method. Complications are common following reconstruction, and the specific type of complication may depend on the technique used. Fracture and graft elongation are associated with use of allograft, whereas button cutout and skin irritation can occur with cortical suture-fixation methods. This technical paper describes an arthroscopically assisted acute AC joint reconstruction technique using the Infinity-Lock Button System. This technique provides a minimally invasive, low-profile reconstruction that may minimize risk of clavicle and coracoid fracture as well as overlying skin irritation. Acute reconstruction may permit healing of the native coracoclavicular and AC ligaments and mitigate risk of future AC joint arthritis.

The Effect of Acromioplasty on the Critical Shoulder Angle and Acromial Index.

PURPOSE: To evaluate the effect of acromioplasty using a cutting block technique on bony coverage as measured by the critical shoulder angle (CSA) and acromial index (AI). METHODS: This study is a retrospective radiographic review using data from a previous prospective randomized clinical trial that offered enrollment to patients aged 18 years or older with a full-thickness tear of the superior rotator cuff between October 2007 and January 2011. Each patient was allocated to repair with either acromioplasty using a cutting block technique or non-acromioplasty treatment arms in a blinded fashion. Medical and demographic information was recorded for each patient. Between January 2017 and December 2017, patients were contacted for repeat follow-up clinical evaluation and radiographs. Measurements of acromial index and critical shoulder angle were performed on pre- and postoperative radiographs by a single reviewer. RESULTS: Seventy-one (75%) patients were available for follow up. The 2 groups were similar in terms of baseline demographics and acromial type. When compared with preoperative measures, acromioplasty did not result in significant reductions in mean CSA (34.5° vs 35.5°; P = .293) or AI (0.68 vs 0.66; P = .283). Furthermore, postoperative CSA (34.5° vs 36.2°, P = .052) and AI (0.66 vs 0.67, P = .535) demonstrated no statistically significant differences between patients with and without acromioplasty, respectively. CONCLUSIONS: There was no statistically significant change in either the CSA or AI following acromioplasty, nor was there a significant postoperative difference in CSA or AI between the group that underwent acromioplasty and the group that did not. CLINICAL RELEVANCE: Some studies suggest a greater postoperative CSA may result in greater risk of retear after arthroscopic rotator cuff repair. The CSA and AI may not be modifiable with acromioplasty.

Next-generation sequencing for diagnosis of infection: is more sensitive really better?

BACKGROUND: The utility of next-generation sequencing (NGS) in differentiating between active infection and contaminant or baseline flora remains unclear. The purpose of this study is to compare NGS with culture-based methods in primary shoulder arthroplasty. METHODS: A prospective series of primary shoulder arthroplasty patients with no history of infection or antibiotic use within 60 days of surgery was enrolled. All patients received standard perioperative antibiotics. After skin incision, a 10 × 3-mm sample of the medial skin edge was excised. A 2 × 2-cm synovial tissue biopsy was taken from the rotator interval after subscapularis takedown. Each sample set was halved and sent for NGS and standard cultures. RESULTS: Samples from 25 patients were analyzed. Standard aerobic/anaerobic cultures were positive in 10 skin samples (40%, 95% confidence interval [CI] 20%-60%) and 3 deep tissue samples (12%, 90% CI 1%-23%]). NGS detected ≥1 bacterial species in 17 of the skin samples (68%, 95% CI 49%-87%) and 7 deep tissue samples (28%, 95% CI 9%-47%). There was a significant difference (P < .03) in the mean number of bacterial species detected with NGS between the positive standard culture (1.6 species) and the negative standard culture groups (5.7 species). CONCLUSION: NGS identified bacteria at higher rates in skin and deep tissue samples than standard culture did in native, uninfected patients undergoing primary procedures. Further research is needed to determine which NGS results are clinically relevant and which are false positives before NGS can be reliably used in orthopedic cases.

Lesser Tuberosity Avulsion Fracture Repair Using Knotless Arthroscopic Fixation.

Although some literature may suggest that acute nondisplaced lesser tuberosity fractures should undergo nonoperative management, there is a body of evidence that supports surgical stabilization of these injuries due to concern for fracture displacement, nonunion and malunion, anteromedial impingement, and possible biceps tendon subluxation or dislocation. In this Technical Note, we introduce a novel technique for arthroscopic fixation of lesser tuberosity avulsion fractures using a knotless repair. In the lateral decubitus position using standard arthroscopic portals, with the addition of the biceps accessory portal, 2 ULTRATAPE sutures are fixed to the avulsed fragment in luggage-tag fashion to create a secure, knotless fixation. These are used to mobilize and anatomically approximate the lesser tuberosity to the avulsion bed and are held in place with suture anchors placed immediately adjacent to the fracture bed. This technique provides good anatomic reduction with maximal surface area for bone-to-bone healing.

Blastomycosis infection of the knee treated with staged total knee arthroplasty.

Blastomycosis is a rare fungal disease that can cause intraarticular infection and joint destruction requiring surgical reconstruction. We describe a patient who presented with destruction of the knee joint of unknown etiology. The patient was initially treated with debridement and spacer placement followed by antifungal therapy after cultures grew blastomycosis. Following adequate treatment of the infection, the patient was taken back to the operating room for reconstruction with a total knee arthroplasty. The patient had a successful outcome with no evidence of infection at two years following surgery. To our knowledge, this case report represents the first documented case in which a blastomycotic infection of a native knee was successfully treated with a two-stage total knee arthroplasty.

Creatine loading elevates the intracellular phosphorylation potential and alters adaptive responses of rat fast-twitch muscle to chronic low-frequency stimulation.

This study tested the hypothesis that elevating the intracellular phosphorylation potential (IPP = [ATP]/[ADP]free) within rat fast-twitch tibialis anterior muscles by creatine (Cr) loading would prevent fast-to-slow fibre transitions induced by chronic low-frequency electrical stimulation (CLFS, 10 Hz, 12 h/day). Creatine-control and creatine-CLFS groups drank a solution of 1% Cr + 5% dextrose, ad libitum, for 10 days before and during 10 days of CLFS; dextrose-control and dextrose-CLFS groups drank 5% dextrose. Cr loading increased total Cr (P < 0.025), phosphocreatine (PCr) (P < 0.003), and the IPP (P < 0.0008) by 34%, 45%, and 64%, respectively. PCr and IPP were 46% (P < 0.002) and 76% (P < 0.02) greater in creatine-CLFS than in dextrose-CLFS. Higher IPP was confirmed by a 58% reduction in phospho-AMP-activated protein kinase α (Thr172) (P < 0.006). In dextrose-CLFS, myosin heavy chain (MyHC) I and IIa transcripts increased 32- and 38-fold (P < 0.006), respectively, whereas MyHC-IIb mRNA decreased by 75% (P < 0.03); the corresponding MyHC-I and MyHC-IIa protein contents increased by 2.0- (P < 0.03) and 2.7-fold (P < 0.05), respectively, and MyHC-IIb decreased by 30% (P < 0.03). In contrast, within creatine-CLFS, MyHC-I and MyHC-IIa mRNA were unchanged and MyHC-IIb mRNA decreased by 75% (P < 0.003); the corresponding MyHC isoform contents were not altered. Oxidative reference enzymes were similarly elevated (P < 0.01) in dextrose-CLFS and creatine-CLFS, but reciprocal reductions in glycolytic reference enzymes occurred only in dextrose-CLFS (P < 0.02). Preservation of the glycolytic potential and greater SERCA2 and parvalbumin contents in creatine-CLFS coincided with prolonged time to peak tension and half-rise time (P < 0.01). These results highlight the IPP as an important physiological regulator of muscle fibre plasticity and demonstrate that training-induced changes typically associated with improvements in muscular endurance or increased power output are not mutually exclusive in Cr-loaded muscles.

Intraoperative frozen section analysis for failed metal-on-metal total hip arthroplasty: is it useful?

Recent failure mechanisms seen with metal-on-metal (MOM) total hip arthroplasty (THA) include a spectrum of inflammatory and immune-mediated reactions of lymphocyte predominance. Frozen section (FS) analysis has been used to evaluate joints for acute inflammation indicative of infection. However, the impact of the inflammatory response to metal debris on FS analysis is unknown and the usefulness of FS analysis in failed MOM THA has not been reported. This study investigated the impact of intraoperative FS analysis in evaluating the possibility of infection in 30 patients undergoing revision of a failed MOM THA. The authors' experience suggests that FS has acceptable specificity (96.6%) for infection in revision MOM surgery, although one false positive was noted in this series and the addition of FS did not provide obvious diagnostic utility. The authors believe that FS should be used selectively (if at all) in conjunction with other studies to avoid misdiagnosis in failed MOM THA.

Medical male circumcision and herpes simplex virus 2 acquisition: posttrial surveillance in Kisumu, Kenya.

BACKGROUND: We estimated the 72-month efficacy of medical male circumcision (MMC) against herpes simplex virus 2 (HSV-2) incidence among men in the Kisumu MMC randomized trial. METHODS: From 2002 to 2005, 2784 men aged 18-24 were enrolled and randomized 1:1 to immediate circumcision or control. Cox proportional hazards regression incorporating stabilized inverse probability of treatment and censoring weights generated through marginal structural modeling was used to estimate the efficacy of MMC on HSV-2 risk. Conventional conditional Cox regression identified multivariable risks for HSV-2 seroconversion. RESULTS: Among 2044 HSV-2 seronegative men at baseline, the cumulative 72-month HSV-2 incidence was 33.5% (32.7% among circumcised men, 34.6% among uncircumcised men). In weight-adjusted Cox regression, the hazard ratio was 0.88 (95% confidence interval, .77-1.10). In multivariable analyses, risks for HSV-2 included human immunodeficiency virus (HIV) infection, genital ulcer disease (GUD), penile epithelial trauma, multiple recent sex partners, and being married /cohabiting. CONCLUSIONS: MMC had no effect on acquisition of HSV-2 during 72 months of follow-up. The temporal sequence and limited correlation between HSV-2, GUD, and penile epithelial trauma suggests that these are distinct phenomena rather than misclassification of HSV-2 symptoms. Determining the etiology of non-sexually transmitted infection GUD and penile epithelial trauma is needed, as both are commonly occurring risks for HSV-2 and HIV acquisition. CLINICAL TRIALS REGISTRATION: NCT0005937.

The long-term efficacy of medical male circumcision against HIV acquisition.

BACKGROUND: In three randomized trials, medical male circumcision (MMC) reduced HIV acquisition in heterosexual men in sub-Saharan Africa by approximately 60%, after 21-24 months of follow-up. We estimated the 72-month efficacy of MMC against HIV among men retained in the Kisumu randomized trial, in which HIV acquisition was reduced by 60% after 24 months. METHODS: From 2002 to 2005, 2784 men aged 18-24 were enrolled and randomized 1 : 1 to immediate circumcision or control. At trial end in December 2006, control men were offered free circumcision. Follow-up continued to September 2010. Cox proportional hazards regression incorporating stabilized inverse probability of treatment and censoring weights generated through marginal structural modeling, was used to account for potential time-varying confounding and censoring to estimate the efficacy of MMC on HIV risk. RESULTS: The cumulative 72-month HIV incidence was 7.21% [95% confidence interval (CI): 5.98-8.68%]: 4.81% among circumcised men, 11.0% among uncircumcised men. The crude hazard ratio of HIV seroconversion for circumcised vs. uncircumcised men was 0.38 [95% CI: 0.26-0.55]. In weight-adjusted Cox regression, the hazard ratio was 0.42 [95% CI: 0.26-0.66]. CONCLUSION: The efficacy of MMC was sustained at 58% at 72 months, similar to overall findings of the three trials under conditions of randomization. These findings provide an estimate of the long-term efficacy of circumcision against HIV acquisition. Our results support programmatic scale-up recommendations that are based on assumptions of sustained efficacy.