Epidemiology of Stingers in the National Football League, 2015-2019.

BACKGROUND: Transient traumatic neuropraxia of either the brachial plexus or cervical nerve root(s) is commonly described as a "stinger" or "burner" by the athlete. Stingers in American Football commonly occur acutely as isolated injuries; however, concomitant injuries, including cervical spine pathologies, have also been reported. HYPOTHESIS: Among National Football League (NFL) athletes, the incidence rate of stingers is higher during the regular season than during the preseason and among positions with high velocity impacts such as running backs, linebackers, defensive backs, and receivers. STUDY DESIGN: Retrospective epidemiology study. LEVEL OF EVIDENCE: Level 4. METHODS: Aggregation of all in-game injuries with a clinical impression of "neck brachial plexus stretch" or "neck brachial plexus compression" entered into the NFL injury surveillance database through the centralized league-wide electronic medical record system over 5 years (2015-2019 seasons). Incidence rates per player-play were calculated and reported. RESULTS: A total of 691 in-game stingers occurred during the study period, with a mean of 138.2 per year. Average single-season injury risk for incident stinger was 3.74% (95% CI, 3.46%-4.05%). The incidence rate was higher during regular season games than during preseason games (12.26 per 100,000 player-plays [11.30-13.31] vs 8.87 [7.31-10.76], P < 0.01, respectively). The highest reported stinger incidence rates were among running backs and linebackers (both >15 per 100,000 player-plays). Among stingers, 76.41% did not miss time. Of those that resulted in time lost from football activities, mean time missed due to injury was 4.79 days (range, 3.17-6.41 days). Concomitant injuries were relatively low (7.09%). CONCLUSION: In-game stinger incidence was stable across the study period and occurred most frequently in running backs and linebackers. Stingers were more common during the regular season, and most players did not miss time. Concomitant injuries were relatively rare. CLINICAL RELEVANCE: An improved understanding of the expected time loss due to stinger and concomitant injuries may provide insight for medical personnel in managing these injuries.

Allograft Anterior Cruciate Ligament Reconstruction Fails at a Greater Rate in Patients Younger Than 34 Years.

Purpose: To characterize the secondary anterior cruciate ligament (ACL) injury rates after primary allograft anterior cruciate ligament reconstruction (ACLR) and to identify the age cut-score at which the risk of allograft failure decreases. Methods: All patients who underwent primary ACLR within a single orthopaedic department between January 2005 and April 2020 were contacted at a minimum of 2 years post-ACLR to complete a survey regarding complications experienced post-surgery, activity level, and perceptions of knee health. Patients were excluded for incidence of previous ACLR (ipsilateral or contralateral) and/or age younger than 14 years. Relative proportions were calculated, binary regression analysis was performed, and receiver operating characteristic analysis was used to identify the threshold age for maximal sensitivity and specificity to predict high risk of allograft failure, defined as undergoing revision ACLR. Results: Of the 939 surveys completed, 398 patients underwent primary allograft ACLR (mean age 39.5 years; range 16.0-66.1 years; 54.3% female). The secondary ACL injury rate was 11.6% (5.8% ipsilateral revision ACLR, 5.8% contralateral ACL injury). Male and female patients had similar revision (5.5% male, 6.0% female, P = .82) and contralateral ACL injury rates (6.6% male, 5.1% female, P = .52). Receiver operating characteristic analysis indicated that age ≤34 years was threshold for differentiating high risk of allograft failure (area under the curve 0.65, 95% confidence interval 0.55-0.76; P = .014). Patients aged ≤34 years had a greater secondary injury rate than patients >34 years (20.4% (10.2% revision ACLR, 10.2% contralateral ACL injury) versus 6.9% (3.5% revision ACLR, 3.5% contralateral ACL injury; P < .001). Binary regression analysis demonstrated that decreasing age was associated with increased risk of graft failure (χ2 = 7.9, P = .02.). Conclusions: Allograft ACLR showed similar failure rates between sexes but displayed suboptimal graft failure outcomes in younger and active patients. By age 34 years, the increased revision risk for younger patients diminished. Level of Evidence: Level IV, therapeutic case series.

Editorial Commentary: Limited Preoperative Range of Motion Is Associated With Range of Motion Deficits After Anterior Cruciate Ligament Reconstruction: "If the Knee Is Not Straight, Wait".

Optimal timing of anterior cruciate ligament reconstruction (ACLR) remains under debate. Prolonging time between injury and ACLR risks damaging the meniscus and chondral surface, as well as delays return to play. Early ACLR may be associated with postoperative stiffness or arthrofibrosis. We emphasize that optimal timing for ACLR depends on criterion-based return of knee range of motion and quadriceps strength, not a quantitative temporal period. The length of time is far less important that the quality of prereconstruction care provided. Prereconstruction care includes "prehabilitation," including prone hangs focusing on optimizing knee range of motion, postinjury effusion resolution, and mentally preparing the patient for postoperative expectations. Defining preoperative criteria for proceeding with surgery is crucial to decrease the risk of arthrofibrosis. Some patients meet these criteria within 2 weeks, whereas others linger to 10 weeks. Reduction in arthrofibrosis requiring surgical intervention is multifactorial and not solely dependent on the length of time between injury and intervention.

The Use of Biologics in NFL Athletes: An Expert Consensus of NFL Team Physicians.

Background: There is a lack of published information outlining the use of biologics in National Football League (NFL) athletes and limited data to guide biologic treatment strategies. Purpose: To develop a consensus on the use of biologics among NFL team physicians. Study Design: Consensus statement. Methods: A working group of 6 experts convened a consensus process involving NFL team physicians using validated Delphi methodology. Physicians from 32 NFL teams as well as NFL London were invited to take part. This iterative process was used to define statements on the use of biologics in NFL athletes. A recent scoping review exploring biologics in professional athletes was used to inform the first of 3 rounds of surveys, with statements considered under 7 headings: biologics in general, challenges of treating NFL athletes, terminology/nomenclature, autologous blood products, cell-based therapies, guidance for NFL team physicians, and biologic research in the NFL. In addition to rating agreement, experts were encouraged to propose further items or modifications. Predefined criteria were used to refine item lists after each survey. For a consensus within the final round, defined a priori, items were included in the final information set if a minimum of 75% of respondents agreed and fewer than 10% disagreed. Results: Physicians from 26 NFL teams and NFL London responded to the initial invitation to participate in the Delphi process; 88.9% of participating team physicians completed the round 1 survey, with response rates of 87.5% in round 2 and 95.2% in round 3. After 3 rounds, 47 statements reached a consensus. A consensus was achieved that platelet-rich plasma has a positive impact on patellar tendinopathy and on symptoms in early osteoarthritis but not for other indications. NFL team physicians agreed that while cell therapies have the potential to improve symptoms, the misrepresentation of uncharacterized preparations as "stem cells" has contributed to the widespread use of unproven therapies. Conclusion: This study established an expert consensus on 47 statements relating to the use of biologics in NFL athletes. In addition to providing clinical guidance for the use of biologics in NFL athletes, this study identified key areas for future focus including the development of athlete education materials.

Mesenchymal stem cells for subchondral bone marrow lesions: From bench to bedside.

Subchondral bone marrow lesions (BMLs) are areas of disease within subchondral bone that appear as T1 hypointense and T2 hyperintense ill-defined areas of bone marrow on magnetic resonance imaging. The most common bone marrow lesions include subchondral lesions related to osteoarthritis, osteochondral defects, and avascular necrosis. Emerging therapies include autologous biologic therapeutics, in particular mesenchymal stem cells (MSCs), to maintain and improve cartilage health; MSCs have become a potential treatment option for BMLs given the unmet need for disease modification. Active areas in the preclinical research of bone marrow lesions include the paracrine function of MSCs in pathways of angiogenesis and inflammation, and the use of bioactive scaffolds to optimize the environment for implanted MSCs by facilitating chondrogenesis and higher bone volumes. A review of the clinical data demonstrates improvements in pain and functional outcomes when patients with knee osteoarthritis were treated with MSCs, suggesting that BM-MSCs can be a safe and effective treatment for patients with painful knee osteoarthritis with or without bone marrow lesions. Preliminary data examining MSCs in osteochondral defects suggest they can be beneficial as a subchondral injection alone, or as a surgical augmentation. In patients with hip avascular necrosis, those with earlier stage disease have improved outcomes when core decompression is augmented with MSCs, whereas patients in later stages post-collapse have equivalent outcomes with or without MSC treatment. While the evidence for the use of MSCs in conditions with associated bone marrow lesions seems promising, there remains a need for continued investigation into this treatment as a viable treatment option.

Cartilage-penetrating hyaluronic acid hydrogel preserves tissue content and reduces chondrocyte catabolism.

Articular cartilage injuries have a limited healing capacity and, due to inflammatory and catabolic activities, often experience progressive degeneration towards osteoarthritis. Current repair techniques generally provide short-term symptomatic relief; however, the regeneration of hyaline cartilage remains elusive, leaving both the repair tissue and surrounding healthy tissue susceptible to long-term wear. Therefore, methods to preserve cartilage following injury, especially from matrix loss and catabolism, are needed to delay, or even prevent, the deteriorative process. The goal of this study was to develop and evaluate a cartilage-penetrating hyaluronic-acid (HA) hydrogel to improve damaged cartilage biomechanics and prevent tissue degeneration. At time zero, the HA-based hydrogel provided a 46.5% increase in compressive modulus and a decrease in permeability after simulated degeneration of explants (collagenase application). Next, in a degenerative culture model (interleukin-1ß [IL-1ß] for 2 weeks), hydrogel application prior to or midway through the culture mitigated detrimental changes to compressive modulus and permeability observed in non-treated explants. Furthermore, localized loss of proteoglycan was observed in degenerative culture conditions alone (non-treated), but hydrogel administration significantly improved the retention of matrix elements. Finally, NITEGE staining and gene expression analysis showed the ability of the HA gel to decrease chondrocyte catabolic activity. These results highlight the importance of reinforcing damaged cartilage with a biomaterial system to both preserve tissue content and reduce catabolism associated with injury and inflammation.

Knee Injuries in the Elite American Football Player: A Descriptive Pictorial Imaging and Mechanism of Injury Review.

ABSTRACT: Musculoskeletal injuries are common in American football, with an incidence ranging from approximately 10 to 35 per 1000 playing hours. Injuries occur more commonly in games than in practice. Although several studies have analyzed specific injury types in football, this review aims to describe the most common knee injuries sustained by American football players and to review the existing literature pertaining to the radiologic findings used in the diagnosis of these injuries.

Evaluation of the Effectiveness of Newer Helmet Designs with Emergent Shell and Padding Technologies Versus Older Helmet Models for Preserving White Matter Following a Season of High School Football.

We aimed to objectively compare the effects of wearing newer, higher-ranked football helmets (HRank) vs. wearing older, lower-ranked helmets (LRank) on pre- to post-season alterations to neuroimaging-derived metrics of athletes' white matter. Fifty-four high-school athletes wore an HRank helmet, and 62 athletes wore an LRank helmet during their competitive football season and completed pre- and post-season diffusion tensor imaging (DTI). Longitudinal within- and between-group DTI metrics [fractional anisotropy (FA) and mean/axial/radial diffusivity (MD, AD, RD)] were analyzed using tract-based spatial statistics. The LRank helmet group exhibited significant pre- to post-season reductions in MD, AD, and RD, the HRank helmet group displayed significant pre- to post-season increases in FA, and both groups showed significant pre- to post-season increases in AD (p's < .05 [corrected]). Between-group analyses revealed the pre- to post-season increase in AD was significantly less for athletes wearing HRank compared to LRank (p < .05 [corrected]). These data provide in vivo evidence that wearing an HRank helmet may be efficacious for preserving white matter from head impact exposure during high school football. Future prospective longitudinal investigations with complimentary imaging and behavioral outcomes are warranted to corroborate these initial in vivo findings.

Telehealth Can Be Implemented Across a Musculoskeletal Service Line Without Compromising Patient Satisfaction.

Background: The COVID-19 pandemic has led to changes to in-office orthopedic care, with a rapid shift to telemedicine. Institutions' lack of established infrastructure for these types of visits has posed challenges requiring attention to confidentiality, safety, and patient satisfaction. Purpose: The aim of this study was to analyze the feasibility of telemedicine in orthopedics during the pandemic and its effect on efficiency and patient satisfaction. Methods: Patients seen by the Emory University Department of Orthopaedics Sports Medicine and Upper Extremity Divisions via telemedicine from March 23 to April 24, 2020, were contacted by telephone. Each patient was asked to respond to questions on satisfaction, ease of use, and potential future use; satisfaction with telemedicine and previous clinical visits were measured using a modified 5-point Likert scale. Results: Of the 762 patients seen, 346 (45.4%) completed the telemedicine questionnaire. Satisfaction varied by visit type, with average scores of 4.88/5 for in-office clinic visits versus 4.61/5 for telemedicine visits. There was no significant difference among age groups for satisfaction ratings. Patients 65 years old or older reported significantly longer visit times and decreased ease of use with the telemedicine platform. Conclusion: Telemedicine in a large orthopedics department was successfully implemented without compromising patient satisfaction. The use of telemedicine allows many patients to be seen quickly and efficiently without diminishing their musculoskeletal clinical experience.

Rehabilitation of Soft Tissue Injuries of the Hip and Pelvis.

The athlete's hip is complex when it comes to the surrounding musculature-approximately 21 different muscles can cross the hip and pelvis region, all synchronously working to maintain pelvic stability and functional hip activities. Commonly injured muscle groups for high-level athletes include flexors, adductors, abductors, and/or proximal hamstring musculotendinous complex. These muscle groups work in harmony; however, each has an independent function and propensity for injury. Rehabilitation phases for each injury group can be broken down into 3 phases: acute management, strengthening, and return-to-sport or return-to-competition phase. Specific rehabilitation principles and modalities are described for each injury group.

Impact of Insurance and Practice Type on Access to Orthopaedic Sports Medicine.

BACKGROUND: The Patient Protection Affordable Care Act has expanded Medicaid eligibility in recent years. However, the provisions of the act have not translated to improved Medicaid payments for specialists such as orthopaedic surgeons. The number of health care practitioners who accept Medicaid is already decreasing, with low reimbursement rates being cited as the primary reason for the trend. HYPOTHESIS: Private practice orthopaedic groups will see patients with Medicaid or Medicare at lower rates than academic orthopaedic practices, and business days until appointment availability will be higher for patients with Medicaid and Medicare than those with private insurance. STUDY DESIGN: Cross-sectional study. METHODS: Researchers made calls to 2 regular-sized orthopaedic practices, 1 small orthopaedic practice, and 1 academic orthopaedic practice in each of the 50 states in the United States. Callers described a scenario of a recent injury resulting in a bucket-handle meniscal tear and an anterior cruciate ligament tear seen on magnetic resonance imaging at an outside emergency department. For a total of 194 practices, 3 separate telephone calls were made, each with a different insurance type. Data regarding insurance acceptance and business days until appointment were tabulated. Student t tests or analysis of variance for continuous data and χ2 or Fisher exact tests for categorical data were utilized. RESULTS: After completing 582 telephone calls, it was determined that 31.4% (n = 59) did not accept Medicaid, compared with 2.2% (n = 4) not accepting Medicare and 1% (n = 1) not accepting private insurance (P < .001). There was no significant association between type of practice and Medicaid refusal (P = 0.12). Mean business days until appointment for Medicaid, Medicare, and private insurance were 5.3, 4.1, and 2.9, respectively (P < .001). CONCLUSIONS: Access to care remains a significant burden for the Medicaid population, given a rate of Medicaid refusal of 32.2% across regular-sized orthopaedic practices. If Medicaid is accepted, time until appointment was significantly longer when compared with private insurance.

Simultaneous, Bilateral Acute Subscapularis Ruptures and Their Arthroscopic Management.

We present the first known case of bilateral, acute ruptures of the subscapularis tendons following a bicycle accident in a 43-year-old male. He underwent right shoulder arthroscopic, anatomic subscapularis tendon repair two weeks postinjury, with the left side staged for surgical treatment six weeks after the index procedure. Postoperatively, the patient remained in a sling for 6 weeks before advancing with therapy protocols. The interval between arthroscopic treatments allowed for independence with activities of daily living and focused, early therapy for each shoulder. This approach yielded a right-sided constant score of 89 and subjective shoulder value of 90%; the left side was 87 and 90%, respectively, at 33 months postoperatively. The patient's only postoperative complaint was slightly diminished external rotation, a near-universal limitation after unilateral repair. This represents a successful outcome that balances functional independence, concentrated rehabilitation, and adherence to safe indications for primary repair. While bilateral traumatic shoulder injuries in a young person is a rare clinical entity, early and staged treatment can lead to good patient outcomes.

Risk Factors for Manipulation Under Anesthesia and/or Lysis of Adhesions After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: In the currently published literature, a higher risk for developing arthrofibrosis after anterior cruciate ligament (ACL) reconstruction has been reported for female patients, adolescents, early surgery or concomitant procedures, and the use of a patellar tendon autograft. There is a lack of evidence regarding other graft choices or factors. HYPOTHESIS: Multiple risk factors will play a significant role in the development of arthrofibrosis after ACL reconstruction. Specifically, we hypothesized that the risk of manipulation under anesthesia (MUA) and/or lysis of adhesions (LOA) would be affected by graft choice and patient demographic factors. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: The charts of all patients who underwent ACL reconstruction over a 10-year period at a single academic institution were queried from an electronic medical record database and reviewed at a minimum of 6 months after ACL reconstruction, with the collection of demographic and surgical data. The relative risk for undergoing MUA and/or LOA was calculated for each analyzed risk factor. RESULTS: A total of 2424 ACL reconstructions were included, with a chart review at a mean of 56.7 months after surgery (range, 7.6-124.0 months). The rate of MUA and/or LOA for arthrofibrosis was 4.5%. A statistically significantly increased relative risk was found for infection (5.45), hematoma requiring evacuation (3.55), ACL reconstruction with meniscal repair (2.83), use of a quadriceps tendon autograft (2.68), age <18 years (2.39), multiple concomitant procedures (1.69), contact injury (1.62), female sex (1.60), and surgery within 28 days of injury (1.53), and a statistically significantly decreased relative risk was found for revision ACL reconstruction (0.30), age >25 years (0.34), and use of a tibialis anterior allograft (0.36). In the multivariate regression model, the use of a quadriceps tendon autograft (P = .00007), infection (P = .00126), and concomitant meniscal repair (P = .00194) were independent risk factors, whereas revision ACL reconstruction (P = .0024) was an independent protective factor. CONCLUSION: Graft type, infection, concomitant meniscal repair, and primary reconstruction are significant risk factors for undergoing MUA or LOA after ACL reconstruction.

Increasing hip and knee flexion during a drop-jump task reduces tibiofemoral shear and compressive forces: implications for ACL injury prevention training.

Although most ACL injury prevention programmes encourage greater hip and knee flexion during landing, it remains unknown how this technique influences tibiofemoral joint forces. We examined whether a landing strategy utilising greater hip and knee flexion decreases tibiofemoral anterior shear and compression. Twelve healthy women (25.9 ± 3.5 years) performed a drop-jump task before and after a training session (10-15 min) that emphasised greater hip and knee flexion. Peak tibiofemoral anterior shear and compressive forces were calculated using an electromyography (EMG)-driven knee model that incorporated joint kinematics, EMG and participant-specific muscle volumes and patella tendon orientation measured using magnetic resonance imaging (MRI). Participants demonstrated a decrease in peak anterior tibial shear forces (11.1 ± 3.3 vs. 9.6 ± 2.7 N · kg-1; P = 0.008) and peak tibiofemoral compressive forces (68.4 ± 7.6 vs. 62.0 ± 5.5 N · kg-1; P = 0.015) post-training. The decreased peak anterior tibial shear was accompanied by a decrease in the quadriceps anterior shear force, while the decreased peak compressive force was accompanied by decreased ground reaction force and hamstring forces. Our data provide justification for injury prevention programmes that encourage greater hip and knee flexion during landing to reduce tibiofemoral joint loading.

Population pharmacokinetic modeling of plasma and intracellular ribavirin concentrations in patients with chronic hepatitis C virus infection.

Ribavirin, a guanosine analog, is a broad-spectrum antiviral agent. Ribavirin has been a fundamental component of the treatment of hepatitis C virus (HCV) infection for decades, but there is a very limited understanding of the clinical pharmacology of this drug. Furthermore, it is associated with a major dose-limiting toxicity, hemolytic anemia. Ribavirin undergoes intracellular phosphorylation by host enzymes to ribavirin monophosphate (RMP), ribavirin diphosphate (RDP), and ribavirin triphosphate (RTP). The intracellular forms have been associated with antiviral and toxic effects in vitro, but the kinetics of these phosphorylated moieties have not been fully elucidated in vivo. We developed a model to characterize the plasma pharmacokinetics of ribavirin and the difference between intracellular phosphorylation kinetics in red cells (nonnucleated) and in peripheral blood mononuclear cells (nucleated). A time-independent two-compartment model with first-order absorption described the plasma data well. The cellular phosphorylation kinetics was described by a one-compartment model for RMP, with the formation rate driven by plasma concentrations and the first-order degradation rate. RDP and RTP rapidly reached equilibrium with RMP. Concomitant telaprevir use, inosine triphosphatase genetics, creatinine clearance, weight, and sex were significant covariates. The terminal ribavirin half-life in plasma and phosphorylated anabolites in cells was approximately 224 h. We found no evidence of time-dependent kinetics. These data provide a foundation for uncovering concentration-effect associations for ribavirin and determining the optimal dose and duration of this drug for use in combination with newer direct-acting HCV agents. (This study has been registered at ClinicalTrials.gov under registration no. NCT01097395.).

Two fixation methods for acromioclavicular joint reduction during coracoclavicular ligament reconstruction: a biomechanical analysis.

One specimen from each of six pairs of cadaveric shoulders underwent a semitendinosus coracoclavicular ligament reconstruction with a hook plate used for acromioclavicular joint reduction, while on the other specimen a polydioxanone (PDS) suture braid was utilized. Cyclical loading followed by maximal load-to-failure testing was performed. Displacement during cyclical loading, loads to 50% and 100% displacement, stiffness, and maximal load to failure were determined for all specimens. Results showed that the locking hook plate allowed significantly less displacement of the coracoclavicular interval during cyclical loading (3.41 vs. 9.67 mm, p = .0081) and withstood significantly higher loads before both 50% (225.5 vs. 107.7 N, p = .0197) and 100% displacement (410.6 vs. 240.1 N, p = .0077). The locking hook plate was found to be significantly stiffer than the PDS suture braid (28.2 vs. 18.4 N/mm, p = .0029), but there was no difference in maximal load to failure between the two fixation methods (hook plate, 434.4 N; PDS, 476.7 N; p = .76).

Anatomic, Transepiphyseal Anterior Cruciate Ligament Reconstruction.

INTRODUCTION: Our technique for physeal-sparing, anatomic anterior cruciate ligament (ACL) reconstruction reliably produces femoral tunnels that are of adequate length and that safely avoid the femoral physis without the addition of time-consuming surgical methods or substantial utilization of fluoroscopy. STEP 1 PREOPERATIVE PLANNING: Obtain radiographs and MRI of the knee as well as an anteroposterior radiograph of the hand (to obtain a bone age). STEP 2 PATIENT SETUP PORTAL PLACEMENT AND GRAFT HARVEST: The affected knee must be able to flex at least 90° with the end of the operative table lowered, in order to properly visualize the anatomy of the ACL femoral footprint. STEP 3 PREPARE ACL FOOTPRINT AND ESTABLISH FAR ANTEROMEDIAL PORTAL: Maintain soft-tissue remnants at both the femoral and the tibial footprint in order to individualize the anatomy. STEP 4 IDENTIFY EXTRA-ARTICULAR LANDMARKS AND PREPARE FEMORAL TUNNEL: Visualize and palpate your previously marked popliteal sulcus and lateral epicondyle; these landmarks are the crucial extra-articular points for establishing a safe femoral tunnel. STEP 5 PREPARE TIBIAL TUNNEL: The tibial tunnel can be safely drilled in a transphyseal manner in skeletally immature patients. STEP 6 FIX GRAFT: Use the Arthrex ACL TightRope RT for femoral fixation. STEP 7 POSTOPERATIVE CARE: As a skeletally immature athlete differs from a more mature athlete in several important ways, alter the postoperative protocol accordingly. RESULTS: Our clinical experience has corresponded to our MRI-based findings from our original study14, and we have not observed any physeal or chondral injuries leading to growth disturbances from our femoral tunnels. WHAT TO WATCH FOR: IndicationsContraindicationsPitfalls & Challenges.

Priapism induced by boceprevir-CYP3A4 inhibition and α-adrenergic blockade: case report.

A 44-year-old white man presented to the emergency department with a 3-day history of priapism requiring a surgically performed distal penile shunt. A drug-drug interaction is the suspected cause whereby CYP3A4 inhibition by boceprevir led to increased exposures of doxazosin, tamsulosin, and/or quetiapine, resulting in additional α-adrenergic blockade.

Flexor tendon repair rehabilitation protocols: a systematic review.

PURPOSE: To systematically review various flexor tendon rehabilitation protocols and to contrast those using early passive versus early active range of motion. METHODS: We searched PubMed and Cochrane Library databases to identify articles involving flexor tendon injury, repair, and rehabilitation protocols. All zones of injury were included. Articles were classified based on the protocol used during early rehabilitation. We analyzed clinical outcomes, focusing on incidence of tendon rupture and postoperative functional range of motion. We also analyzed the chronological incidence of published tendon rupture with respect to the protocol used. RESULTS: We identified 170 articles, and 34 met our criteria, with evidence ranging from level I to level IV. Early passive motion, including both Duran and Kleinert type protocols, results included 57 ruptures (4%) and 149 fingers (9%) with decreased range of motion of 1598 tendon repairs. Early active motion results included 75 ruptures (5%) and 80 fingers (6%) with decreased range of motion of 1412 tendon repairs. Early passive range of motion protocols had a statistically significantly decreased risk for tendon rupture but an increased risk for postoperative decreased range of motion compared to early active motion protocols. When analyzing published articles chronologically, we found a statistically significant trend that overall (passive and active rehabilitation) rupture rates have decreased over time. CONCLUSIONS: Analyzing all flexor tendon zones and literature of all levels of evidence, our data show a higher risk of complication involving decreased postoperative digit range of motion in the passive protocols and a higher risk of rupture in early active motion protocols. However, modern improvements in surgical technique, materials, and rehabilitation may now allow for early active motion rehabilitation that can provide better postoperative motion while maintaining low rupture rates.

Impact of the CYP2C8 *3 polymorphism on the drug-drug interaction between gemfibrozil and pioglitazone.

AIM: The objective of this study was to determine the extent to which the CYP2C8*3 allele influences pharmacokinetic variability in the drug-drug interaction between gemfibrozil (CYP2C8 inhibitor) and pioglitazone (CYP2C8 substrate). METHODS: In this randomized, two phase crossover study, 30 healthy Caucasian subjects were enrolled based on CYP2C8*3 genotype (n = 15, CYP2C8*1/*1; n = 15, CYP2C8*3 carriers). Subjects received a single 15 mg dose of pioglitazone or gemfibrozil 600 mg every 12 h for 4 days with a single 15 mg dose of pioglitazone administered on the morning of day 3. A 48 h pharmacokinetic study followed each pioglitazone dose and the study phases were separated by a 14 day washout period. RESULTS: Gemfibrozil significantly increased mean pioglitazone AUC(0,∞) by 4.3-fold (P < 0.001) and there was interindividual variability in the magnitude of this interaction (range, 1.8- to 12.1-fold). When pioglitazone was administered alone, the mean AUC(0,∞) was 29.7% lower (P = 0.01) in CYP2C8*3 carriers compared with CYP2C8*1 homozygotes. The relative change in pioglitazone plasma exposure following gemfibrozil administration was significantly influenced by CYP2C8 genotype. Specifically, CYP2C8*3 carriers had a 5.2-fold mean increase in pioglitazone AUC(0,∞) compared with a 3.3-fold mean increase in CYP2C8*1 homozygotes (P = 0.02). CONCLUSION: CYP2C8*3 is associated with decreased pioglitazone plasma exposure in vivo and significantly influences the pharmacokinetic magnitude of the gemfibrozil-pioglitazone drug-drug interaction. Additional studies are needed to evaluate the impact of CYP2C8 genetics on the pharmacokinetics of other CYP2C8-mediated drug-drug interactions.