Drug Administration Clinical Trial Research Articles

Impact of Peridevice Leak on 5-Year Outcomes After Left Atrial Appendage Closure

BackgroundIn the U.S. Food and Drug Administration (FDA) clinical trials of left atrial appendage (LAA) closure, a postimplantation peridevice leak (PDL) of ≤5 mm (PDL≤5) was accepted as sufficient LAA “closure.” However, the clinical consequences of these PDLs on subsequent thromboembolism are poorly characterized. ObjectivesWe sought to assess the impact of PDL≤5 on clinical outcomes after implantation of the Watchman device. MethodsUsing combined data from the FDA studies PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation), PREVAIL (Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation vs Long Term Warfarin Therapy), and CAP2 (Continued Access to PREVAIL), we assessed patients with successful device implantation for PDL by means of protocol-mandated transesophageal echocardiograms (TEEs) at 45 days and 1 year. Five-year outcomes were assessed as a function of the absence or presence of PDL≤5. ResultsThe cohort included 1,054 patients: mean age 74 ± 8.3 years, 65% male, and CHA2DS2-VASc 4.1 ± 1.4. TEE imaging at 45 days revealed 634 patients (60.2%) without and 404 (38.3%) with PDL≤5, and 1-year TEE revealed 704 patients (71.6%) without and 272 (27.7%) with PDL≤5. The presence of PDL≤5 at 1 year, but not at 45 days, was associated with an increased 5-year risk of ischemic stroke or systemic embolism (adjusted HR: 1.94; 95% CI: 1.15-3.29; P = 0.014), largely driven by an increase in nondisabling stroke (HR: 1.97; 95% CI: 1.03-3.78; P = 0.04), while disabling or fatal stroke rates were similar (HR: 0.69; 95% CI: 0.19-2.46; P = 0.56). PDL≤5 was not associated with an increased risk of cardiovascular or unexplained death (HR: 1.20; P = 0.45) or all-cause death (HR: 0.87; P = 0.42). ConclusionsPDL≤5 at 1 year after percutaneous LAA closure with the Watchman device are associated with increased thromboembolism, driven by increased nondisabling stroke, but similar mortality. (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation [PROTECT-AF; NCT00129545]; Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation vs Long Term Warfarin Therapy [PREVAIL; NCT01182441]; Continued Access to PREVAIL [CAP2; NCT01760291])

Results of the United States Food and Drug Administration Clinical Trial of the CustomFlex Artificial Iris

To evaluate safety and efficacy of a custom-manufactured artificial iris device (CustomFlex Artificial Iris; HumanOptics AG) for the treatment of congenital and acquired iris defects. Multicenter, prospective, unmasked, nonrandomized, interventional clinical trial. Patients with photophobia, sensitivity secondary to partial or complete congenital or acquired iris defects, or both. Eyes were implanted from November 26, 2013, to December 1, 2017, with a custom, foldable artificial iris by 1 of 4 different surgical techniques. Patients were evaluated 1 day, 1 week, and 1, 3, 6, and 12 months after surgery. At each examination, slit-lamp findings, intraocular pressure, implant position, subjective visual symptoms, and complications were recorded. Corrected distance visual acuity (CDVA) and endothelial cell density (ECD) were measured at 3, 6, or 12 months as additional safety evaluations. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was used to assess health-related quality of life affected by vision. The Global Aesthetic Improvement Scale was used to assess cosmetic results. Photosensitivity, glare, visual symptoms, NEI VFQ-25 score, Global Aesthetic Improvement Scale rating, prosthesis-related adverse events, intraocular lens (IOL)-related adverse events, and surgery-related adverse events 12 months after surgery. At the 12-month postoperative examination, a 59.7% reduction in marked to severe daytime light sensitivity (P < 0.0001), a 41.5% reduction in marked to severe nighttime light sensitivity (P < 0.0001), a 53.1% reduction in marked to severe daytime glare (P < 0.0001), and a 48.5% reduction in severe nighttime glare (P < 0.0001) were found. A 15.4-point improvement (P < 0.0001) in the NEI VFQ-25 total score was found, and 93.8% of patients reported an improvement in cosmesis as measured by the Global Aesthetic Improvement Scale 12 months after surgery. No loss of CDVA of > 2 lines related to the device was found. Median ECD loss was 5.3% at 6 months after surgery and 7.2% at 12 months after surgery. The artificial iris surpassed all key safety end points for adverse events related to the device, IOL, or implant surgery and metall key efficacy end points, including decreased light and glare sensitivity, improved health-related quality of life, and satisfaction with cosmesis. The device is safe and effective for the treatment of symptoms and an unacceptable cosmetic appearance created by congenital or acquired iris defects.

Cervical Disc Arthroplasty for Axial Neck Pain: Comparison of Outcomes to 2 Other Common Cervical Conditions.

Cervical disc arthroplasty (CDA) is an established treatment for degenerative disc disease with radiculopathy and/or myelopathy. There is, however, little published evidence of its effectiveness to relieve pain and improve function in patients with a primary diagnosis of axial neck pain. Such patients were excluded from all previous Food and Drug Administration clinical trials for CDA. We compare the outcomes of patients who underwent CDA for 3 common cervical conditions from 2003 to 2018. Seven hundred and eighty-two CDA patients at a single site were grouped by primary diagnosis: predominant axial neck pain (ANP) (n = 257), predominant radiculopathy (RAD) (n = 331), or a combination of both (ANP + RAD) (n = 195). Mixed models for repeated measures predicted and analyzed scores at all time points, adjusting for diagnosis group, time point, and, if statistically significant, number of operative levels and demographic characteristics. Outcome measures included the Neck Disability Index, numerical pain scales (intensity plus frequency), the Veterans RAND 12 Item Health Survey (VR-12) Physical Component Score, the Mental Component Score, and reoperations. Patients were assessed preoperatively and postoperatively at 6 weeks, 3 months, 6 months, 1 year, and annually thereafter. At baseline, arm pain scores in the ANP group were statistically lower (P = .0002) than in the RAD and ANP + RAD groups, consistent with preoperative diagnoses. Surgeries included 40.8% 1-level, 41.6% 2-level, 14.7% 3-level, and 2.9% 4-level. For all outcome measures, improvements were statistically significant from baseline to each postoperative time point without statistical difference between the 3 diagnosis groups. In total, 45/782 patients (5.8%) underwent a secondary surgery: 3.5% ANP, 5.8% RAD, and 8.7% ANP + RAD. Days to reoperation did not statistically differ between groups (P = .489). Appropriately selected patients with predominant axial neck pain treated with CDA may achieve clinical and functional outcomes comparable to patients with a primary diagnosis of radiculopathy or of axial neck pain with concomitant radiculopathy. This study provides information that should help clinicians decide whether to offer CDA for patients with a primary diagnosis of axial neck pain and to appropriately counsel such patients about expected outcomes. 4.

Genome-Editing Strategies for Treating Human Retinal Degenerations.

Inherited retinal degenerations (IRDs) are a leading cause of blindness. Although gene-supplementation therapies have been developed, they are only available for a small proportion of recessive IRD mutations. In contrast, genome editing using clustered-regularly interspaced short palindromic repeats (CRISPR) CRISPR-associated (Cas) systems could provide alternative therapeutic avenues for treating a wide range of genetic retinal diseases through targeted knockdown or correction of mutant alleles. Progress in this rapidly evolving field has been highlighted by recent Food and Drug Administration clinical trial approval for EDIT-101 (Editas Medicine, Inc., Cambridge, MA), which has demonstrated efficacious genome editing in a mouse model of CEP290-associated Leber congenital amaurosis and safety in nonhuman primates. Nonetheless, there remains a significant number of challenges to developing clinically viable retinal genome-editing therapies. In particular, IRD-causing mutations occur in more than 200 known genes, with considerable heterogeneity in mutation type and position within each gene. Additionally, there are remaining safety concerns over long-term expression of Cas9 in vivo. This review highlights (i) the technological advances in gene-editing technology, (ii) major safety concerns associated with retinal genome editing, and (iii) potential strategies for overcoming these challenges to develop clinical therapies.

Review of Sexual Preservation After Novel Benign Prostatic Hyperplasia Surgical Treatment Modalities From Food and Drug Administration Clinical Trials.

Traditional benign prostatic hyperplasia treatment options, such as transurethral resection of the prostate and laser, have focused on addressing urinary symptoms for men; however, these options are associated with a high risk of sexual dysfunction. The objective of this study was to assess newer technologies (Aquablation therapy, UroLift, and Rezum) for the treatment of benign prostatic hyperplasia and the impact of preserving sexual function compared with transurethral resection of the prostate. A comprehensive review of Food and Drug Administration randomized studies from each of the technologies was carried out. A comparison of 3-year outcomes for International Index of Erectile Function-5 and Male Sexual Health Questionnaire Ejaculatory Function domain short form was analyzed. Aquablation and prostatic urethral lift were the only therapies to show permanent sexual function preservation in both Male Sexual Health Questionnaire Ejaculatory Function domain short form (ejaculatory function) and International Index of Erectile Function-5 (erectile function) at 3 years after treatment. For prostates less than 80 cc, Aquablation and prostatic urethral lift were able to demonstrate permanent sexual function preservation in both Male Sexual Health Questionnaire Ejaculatory Function domain short form (ejaculatory function) and International Index of Erectile Function-5 (erectile function) at 3 years after treatment. Bhojani N, Yafi FA, Misrai V, etal. Review of Sexual Preservation After Novel Benign Prostatic Hyperplasia Surgical Treatment Modalities From Food and Drug Administration Clinical Trials. Sex Med Rev 2021;9:169-173.

Safety and Efficacy of Colored Iris Reconstruction Lens Implantation

We sought to evaluate the 1- to 9-year safety and efficacy of colored iris reconstruction lens implantation in eyes with visual disturbances caused by partial or complete aniridia. Prospective, interventional case series. Thirty-eight patients were implanted with Ophtec 311 colored iris reconstruction lenses at the University of California, Los Angeles as part of a larger U.S. Food and Drug Administration clinical trial. Patients in group 1 lacked corneal pathology. Patients in group 2 patients had corneal pathology, such as endothelial failure, previous transplants, or scarring. Safety measures included loss of corrected distance visual acuity (CDVA), surgical complications, adverse events, secondary interventions, and corneal endothelial cell loss. Efficacy measures included improvement in uncorrected distance visual acuity (UDVA) and subjective visual disturbances. Groups 1 (n= 8) and 2 (n= 30) showed improvements in CDVA (P= .155 and .038), UDVA (P= .002 and P < .001), and subjective visual disturbance scores at year 3. Median CDVA and UDVA declined slightly for both groups after 1-2 years. Group 2 experienced more adverse events, surgical complications, and secondary interventions. Endothelial cell loss was greater for group 2 (19.7%) than group 1 (8.05%), although this difference was not statistically significant (P= .067). Colored iris reconstruction lens implantation improved CDVA, UDVA, and subjective visual disturbances 3 years postoperatively and beyond. Adverse events, complications, and subsequent declines in visual acuity were common, however, in these eyes with complex medical and surgical histories.

Discussion: The Questionable Role of Antibiotic Irrigation in Breast Augmentation

Discussion: The Questionable Role of Antibiotic Irrigation in Breast Augmentation

More eyes with 20/10 distance visual acuity at 12 months versus 3 months in a topography-guided excimer laser trial: Possible contributing factors

To study eyes with 20/10 uncorrected distance visual acuity (UDVA) 3months and 12months after topography-guided LASIK for myopia and myopic astigmatism, and to identify factors predictive of this excellent level of visual acuity. Nine practices in the USA. Prospective unmasked study of safety and effectiveness. The percentage of eyes with UDVA of 20/10 or better at 3months and 12months after topography-guided laser insitu keratomileusis (LASIK) with the Contoura Vision excimer laser in a U.S. Food and Drug Administration clinical trial was compared, and possible contributing factors were investigated. Preoperatively, only 1% of eyes had 20/10 corrected distance visual acuity (CDVA). Postoperatively, 7.0% of eyes had 20/10 or better UDVA at 3months, and this number increased to 16% at 12months (odds ratio, 2.48; 95% confidence interval, 1.33-4.61). The lower preoperative corneal astigmatism and postoperative refractive cylinder correlated with better postoperative UDVA and CDVA, respectively (P<.01 in all cases). The postoperative UDVA correlated with the postoperative CDVA (P<.01). The number of eyes with UDVA of 20/10 increases significantly between 3months and 12months after topography-guided LASIK and correlates with better postoperative CDVA. Eyes with lower preoperative corneal astigmatism are more likely to achieve 20/10 or better UDVA postoperatively. A significant improvement in the number of eyes with 20/10 or better from 3months to 12months after LASIK might be unique to topography-guided treatment.

Evaluation of the small-aperture intracorneal inlay: Three-year results from the cohort of the U.S. Food and Drug Administration clinical trial

To evaluate the safety and effectiveness of the Kamra small-aperture intracorneal inlay. Centers in North America, Europe, Asia, and Australia. Prospective clinical trial. Patients with emmetropic presbyopia had intracorneal implantation of the inlay in the nondominant eye. The study comprised 507 patients with emmetropic presbyopia who were aged 45 to 60years old. The implanted eyes exhibited 3.5 diopters of defocus range above 20/40, with 363 (87.1%) of 417 patients and 391 (93.8%) of 417 patients having 20/40 or better monocular and binocular uncorrected near visual acuity (UNVA) at 36months, respectively. Patients implanted via a femtosecond laser pocket procedure using a spot/line setting of 6μm×6μm demonstrated further improved near vision, with 131 (90.3%) of 145 patients and 137 (94.5%) of 145 of patients having 20/40 or better monocular and binocular UNVA, respectively. Uncorrected distance visual acuity 20/25 or better was maintained in 135 (93.1%) of 145 of implanted eyes and 100% (145) of 145 of implanted eyes binocularly at 36months. Less than 1.5% of eyes had a loss of 2 or more lines of corrected distance visual acuity for 3months or more at any time after surgery. Forty-four inlays (8.7%) were removed from the full cohort over 3years. The removal rate was significantly less in the 6×6 pocket group (3.0% for visual complaints) and further reduced with deeper implantation (0%). Less than 1.0% of the patients reported severe glare or halos postoperatively. The small-aperture corneal inlay was found to be safe and effective, improving near vision both monocularly and binocularly with minimal effect on distance visual acuity.

Double-Sided Personality: Effects of Arsenic Trioxide on Inflammation.

In 1992, arsenic trioxide (As2O3, ATO) was demonstrated to be an effective therapeutic agent against acute promyelocytic leukemia (APL), rekindling attention to ATO applications in U.S. Food and Drug Administration clinical trials for the treatment of cancers, such as leukemia, lymphomas, and solid tumors. ATO is a potent chemotherapeutic drug that can also be used to treat other diseases, such as autoimmune diseases, because it affects multiple pathways including apoptosis induction, differentiation stimulation, and proliferation inhibition. As inflammation is a critical component of disease progression, ATO is a feasible treatment option based on its ability to protect against inflammation. However, ATO is also a well-known carcinogen because of its pro-inflammatory effect. This review will focus on the double-sided effects of ATO on inflammation as well as the relevant mechanisms underlying these effects, aiming to provide a rational understanding of how ATO effects the immune system. We especially aim to provide a comprehensive overview of our current knowledge of how ATO influences inflammation.

Minimally invasive mitral valve repair

### Learning objectives Modified cardiopulmonary bypass techniques, including vacuum-assisted venous drainage, were introduced in 1995 and enabled safe and effective minimally invasive mitral valve (MV) surgery. Approaches have evolved since...

Pharmacoeconomics: Growth in Cancer Diagnostics Means Market Opportunity

Testing for precision diagnostics in cancer is underway in Food and Drug Administration clinical trials. This new technology will outdate current, inaccurate technologies (i.e., mammograms and prostate-specific antigen tests) and become part of routine health screenings. Cost savings translate to bigger profit potential for hospitals and laboratories that conduct the tests. Trends in precision medicine will turn the diagnostics sector from its current moderate value/moderate growth status to one replicating the explosive growth of biotech. <b>TOPICS:</b>Private equity, legal/regulatory/public policy, portfolio construction, other real assets

Fourteen Year Follow-Up of Randomized Clinical Trials of Active Robotic-Assisted Total Hip Arthroplasty

BackgroundActive robotic total hip arthroplasty (THA) has been used clinically for over 20 years, but long-term results have never been studied. The aims of this study are to determine whether active robotic THA improves clinical outcomes and results in fewer revisions over a long-term follow-up. MethodsPatients from 2 US Food and Drug Administration clinical trials (1994-1998 and 2001-2006) who had undergone THA using either an active robotic system or a traditional manual technique were examined to determine if any differences existed in radiographic analysis and patient pain and function using the University of California, Los Angeles; visual analog scale; Health Status Questionnaire (HSQ) pain; HSQ role physical; HSQ physical functioning; Harris pain scores; and the total Western Ontario and McMaster Universities Osteoarthritis Index scores at a mean follow-up of 14 years. ResultsThe ROBODOC group had statistically significant higher HSQ pain and Harris pain scores and lower Western Ontario and McMaster Universities Osteoarthritis Index scores. There was no statistically significant difference in probability of a revision for wear between the groups (χ2 = 1.80; P = .179), and no revisions for loosening in either group. ConclusionPrior studies have demonstrated improved implant fit and alignment with the use of this active robot system. This long-term study now shows no failures for stem loosening at a mean follow-up of 14 years and small but potentially important improvements in clinical outcomes in the robot group.

Bilateral implantation of +3.0 D multifocal toric intraocular lenses: results of a US Food and Drug Administration clinical trial.

PurposeThe purpose of this study was to evaluate the clinical outcomes of apodized diffractive +3.0 D multifocal toric intraocular lens (IOL) implantations in subjects with preoperative corneal astigmatism.Patients and methodsThis was a prospective cohort study conducted at 21 US sites. The study population consisted of 574 subjects, aged ≥21 years, with preoperative astigmatism 0.75–2.82 D, and potential postoperative visual acuity (VA) ≥0.2 logMAR, undergoing bilateral cataract removal by phacoemulsification. The intervention was bilateral implantation of aspheric apodized diffractive +3.0 D multifocal toric or spherical multifocal nontoric IOLs. The main outcome measures were monocular uncorrected near and distance VA and safety at 12 months.ResultsA total of 373/386 and 182/188 subjects implanted with multifocal toric and nontoric IOLs, respectively, completed 12-month follow-up after the second implantation. Toric IOLs were nonin-ferior in monocular uncorrected distance (4 m) and near (40 cm) VA but had >1 line better binocular uncorrected intermediate VA (50, 60, and 70 cm) than nontoric IOLs. Toric IOLs reduced cylinder to within 0.50 D and 1.0 D of target in 278 (74.5%) and 351 (94.1%) subjects, respectively. Mean ± standard deviation (SD) differences between intended and achieved axis orientation in the first and second implanted eyes were 5.0°±6.1° and 4.7°±4.0°, respectively. Mean ± SD 12-month IOL rotations in the first and second implanted eyes were 2.7°±5.8° and 2.2°±2.7°, respectively. No subject receiving toric IOLs required secondary surgical intervention due to optical lens properties.ConclusionMultifocal toric IOLs were noninferior to multifocal nontoric IOLs in uncorrected distance and near VAs in subjects with preexisting corneal astigmatism and effectively corrected astigmatism of 0.75–2.82 D.

Pharmacokinetics and Safety of Tedizolid after Single and Multiple Intravenous/Oral Sequential Administrations in Healthy Chinese Subjects

PurposeTedizolid phosphate is a new antibacterial agent under investigation for the treatment of Gram-positive infections in China. This study was conducted to assess the pharmacokinetic (PK) properties, oral bioavailability, and safety of once daily tedizolid phosphate 200 mg in Chinese subjects to support its further clinical development in China. MethodsThis Phase I single-center study, conducted in 16 healthy Chinese male subjects, consisted of a single-dose administration, 1:1 randomized, two-way, intravenous (IV)/oral (PO) crossover of tedizolid phosphate 200 mg (Part 1) and, after a 7-day washout, a nonrandomized, multiple-dose, 7-day tedizolid phosphate 200 mg once daily administration (IV for 3 days, PO for 4 days; Part 2). Blood samples were collected for up to 72 hours after single dosing and for up to 2 hours on Day 3 and 72 hours on Day 7 of multiple dosing to determine PK parameters. Adverse events (AEs) were recorded throughout the entire study. FindingsThe Cmax and AUC of tedizolid (the active moiety of tedizolid phosphate) were 3.02 µg/mL and 30.50 µg • h/mL after single IV dosing of tedizolid phosphate, and 2.25 µg/mL and 26.10 µg • h/mL after single PO dosing, respectively, and the mean half-life was 10.1 hours for both administration routes. The oral bioavailability of tedizolid was 85.5%. PK parameters of tedizolid were similar after single and multiple dosing of tedizolid phosphate, indicating no time dependency. Only minor accumulation of tedizolid was observed after multiple dosing (expressed as accumulation ratios RAAUC: 1.18 for PO dosing, and RACmax: 1.16 and 1.05 for IV and PO dosing, respectively). Steady state of tedizolid was reached after about 3 days, and trough concentrations remained constant when switching from IV to PO dosing. Tedizolid phosphate was well tolerated with 6 subjects (37.5%) in Part 1 and 5 subjects (31.3%) in Part 2 experiencing an AE; all AEs but one were related to the study drug assessed by the investigator. All AEs were of mild intensity and had recovered or resolved by the end of the study. No serious AEs were observed, and no subjects prematurely discontinued the study due to an AE. ImplicationsThe results of this Phase I study conducted in Chinese male subjects indicate that no dosage adjustment of tedizolid phosphate 200 mg would be required when switching administration routes in this population. Tedizolid phosphate was well tolerated in healthy Chinese subjects. China Food and Drug Administration clinical trial permission numbers 2014L00360 and 2014L00361.

Results of topography-guided laser in situ keratomileusis custom ablation treatment with a refractive excimer laser

To evaluate the safety and effectiveness of topography-guided custom ablation treatment (T-CAT) to correct myopia and myopic astigmatism with laser in situ keratomileusis (LASIK). Nine clinical sites in the USA. Prospective observational nonrandomized unmasked study. The study comprised patients aged 18 to 65 years old with myopia or myopic astigmatism with a manifest refraction spherical equivalent (MRSE) up to -9.0 diopters (D) and astigmatism of 6.0 D or less. Patients with previous refractive surgery or abnormal topography were excluded. Corneal topographies were obtained using the Allegro Topolyzer, and laser treatment was delivered with the Allegretto Wave Eye-Q excimer laser system. Visual outcomes were evaluated postoperatively at 1 day, 1 week, and 1, 3, 6, 9, and 12 months. The clinical trial enrolled 212 patients (249 eyes). The T-CAT procedure significantly reduced the MRSE and cylinder, with stability of outcomes evident from 3 to 12 months after surgery. Compared with the preoperative corrected distance visual acuity (CDVA), the postoperative uncorrected distance visual acuity (UDVA) improved by 1 line or more in 30% of eyes and the postoperative UDVA was at least as good as the preoperative CDVA in 90% of eyes. Most visual symptoms improved after T-CAT. There were no significant treatment-related adverse events or loss of vision. The T-CAT procedure performed with the diagnostic device and the refractive excimer laser system safely and effectively achieved predictable refractive outcomes and reduced visual symptoms with stable results through 12 months. Dr. Stulting is a paid consultant to Alcon Laboratories, Inc., and was a medical monitor for the U.S. Food and Drug Administration (FDA) clinical trial. Dr. Fant is president of Clinical Research Consultants, Inc. (CRC), the clinical and regulatory consulting group that sponsored the FDA clinical trial. Dr. Fant and CRC were supported by Alcon Laboratories, Inc.

Discussion: Anaplastic large cell lymphoma occurring in women with breast implants: analysis of 173 cases.

Dallas, Texas From the Department of Plastic Surgery, University of Texas Southwestern Medical Center; and private practice. Received for publication November 8, 2014; accepted November 11, 2014. Disclosure: The author is an education advisor for Allergan and Sientra and an investigator for U.S. Food and Drug Administration clinical trials for Mentor and Allergan. William P. Adams, Jr., M.D., Department of Plastic Surgery, UT Southwestern Medical Center, 6901 Snider Plaza, Suite 120, Dallas, Texas 75205, [email protected]

Collective commentaries regarding two articles disputing value of cervical disc arthroplasty vs. Anterior cervical diskectomy and fusion.

Collective commentaries regarding two articles disputing value of cervical disc arthroplasty vs. Anterior cervical diskectomy and fusion.

Very Late Complications of Cervical Arthroplasty

Prospective, single-site, randomized, Food and Drug Administration-approved investigational device exemption clinical trials of 2 cervical arthroplasty (CA) devices. To evaluate complications with CA occurring more than 4 years after the surgical procedure in Food and Drug Administration clinical trials of the Bryan and Prestige LP arthroplasty devices. Reports of several randomized clinical studies have shown CA to be a safe and effective alternative to anterior cervical fusion in the treatment of degenerative cervical disc disorders. A majority include follow-up intervals of 4 years or less. Between 2002 and 2006, 94 patients were enrolled in Food and Drug Administration studies of the Bryan and Prestige LP cervical disc devices. Charts, imaging studies, and hospital records were reviewed for those who underwent arthroplasty and returned more than 4 years after their surgical procedure with neck-related pain or dysfunction. Excluding adjacent segment disease that occurred with a similar rate for patients who underwent fusion and arthroplasty, 5 patients, all treated with arthroplasty, returned for evaluation of neck and arm symptoms between 48 and 72 months after surgery. Four patients had peridevice vertebral body bone loss. One patient had posterior device migration and presented with myelopathy. Three required revision surgery and 2 were observed. Four patients maintained follow-up and reported stabilization or improvement in symptoms. Despite their similarities, CA and fusion are not equivalent procedures in this study in regard to very late complications. Similar to large joint arthroplasty, delayed device-related complications may occur with CA. These complications commenced well beyond the time frame for complications associated with more traditional cervical spine procedures. Both patients and surgeons should be aware of the potential for very late device-related complications occurring with CA and the need for revision surgery. 1.

Multilevel Arthroplasty for Cervical Spondylosis

Retrospective cohort study. To investigate the differences between single- and multilevel degenerative disc diseases (DDDs) treated with cervical arthroplasty. The US Food and Drug Administration clinical trials compared arthroplasty with anterior cervical discectomy and fusion for single-level DDD. However, cervical arthroplasty for multilevel DDD is rarely addressed in the literature. A total of 102 consecutive patients who underwent Bryan arthroplasty were divided into either a single- or multilevel group. Clinical outcomes were measured by the visual analogue scale (VAS) of neck and arm, and by the neck disability index with a minimum follow-up of 25 months. Every patient had radiographical evaluations, and computed tomography. Eighty-six patients (84.3%) completed the follow-up with a mean time of 38.3 ± 8.7 months. Postoperatively, there were significant improvements in clinical outcomes (i.e., VAS neck, VAS arm, and neck disability index) at each time point of evaluation (i.e., 3-, 6-, 12-, and 24 mo postoperation). The sex composition and clinical outcome improvements between the single- and multilevel groups were not significantly different. The multilevel group was older (51.3 ± 8.6 vs. 46.3 ± 11.2 yr; P = 0.02), had more intraoperative blood loss (218.0 ± 182.4 vs. 102.8 ± 79.2 mL; P = 0.001), and demonstrated a higher rate of heterotopic ossification (HO) than the single-level group (66.0% vs. 25.0%; P < 0.001). The majority (97.7%) of the artificial discs in this series remained mobile despite HO. Clinical outcomes of cervical arthroplasty in multilevel spondylosis are similar to single-level outcomes. However, the significantly higher rate of HO found in multilevel arthroplasty and its long-term effect warrant further investigation.