Intra-articular cellular therapy injections constitute an appealing strategy that may modify the intra-articular milieu or regenerate cartilage in the settings of osteoarthritis and focal cartilage ...defects. However, little consensus exists regarding the indications for cellular therapies, optimal cell sources, methods of preparation and delivery, or means by which outcomes should be reported.
We present a systematic review of the current literature regarding the safety and efficacy of cellular therapy delivered by intra-articular injection in the knee that provided a Level of Evidence of III or higher. A total of 420 papers were screened. Methodological quality was assessed using a modified Coleman methodology score.
Only 6 studies (4 Level II and 2 Level III) met the criteria to be included in this review; 3 studies were on treatment of osteoarthritis and 3 were on treatment of focal cartilage defects. These included 4 randomized controlled studies without blinding, 1 prospective cohort study, and 1 retrospective therapeutic case-control study. The studies varied widely with respect to cell sources, cell characterization, adjuvant therapies, and assessment of outcomes. Outcome was reported in a total of 300 knees (124 in the osteoarthritis studies and 176 in the cartilage defect studies). Mean follow-up was 21.0 months (range, 12 to 36 months). All studies reported improved outcomes with intra-articular cellular therapy and no major adverse events. The mean modified Coleman methodology score was 59.1 ± 16 (range, 32 to 82).
The studies of intra-articular cellular therapy injections for osteoarthritis and focal cartilage defects in the human knee suggested positive results with respect to clinical improvement and safety. However, the improvement was modest and a placebo effect cannot be disregarded. The overall quality of the literature was poor, and the methodological quality was fair, even among Level-II and III studies. Effective clinical assessment and optimization of injection therapies will demand greater attention to study methodology, including blinding; standardized quantitative methods for cell harvesting, processing, characterization, and delivery; and standardized reporting of clinical and structural outcomes.
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Patients with tetralogy of Fallot are at risk for ventricular arrhythmias and sudden cardiac death. These abnormalities are associated with pulmonary regurgitation, right ventricular enlargement, and ...a substrate of discrete, slowly-conducting isthmuses. Although these arrhythmic events are rare, their prediction is challenging. This review will address contemporary risk assessment and prevention strategies. Numerous variables have been proposed to predict who would benefit from an implantable cardioverter-defibrillator. Current risk stratification models combine independently associated factors into risk scores. Cardiac magnetic resonance imaging, QRS fragmentation assessment, and electrophysiology testing in selected patients may refine some of these models. Interaction between right and left ventricular function is emerging as a critical factor in our understanding of disease progression and risk assessment. Multicenter studies evaluating risk factors and risk mitigating strategies such as pulmonary valve replacement, ablative strategies, and use of implantable cardiac-defibrillators are needed moving forward.
Use of platelet-rich-plasma (PRP) injections for treating knee osteoarthritis has increased over the past decade. We used cost-effectiveness analysis to evaluate the value of PRP in delaying the need ...for total knee arthroplasty (TKA).
We developed a Markov model to analyze the baseline case: a 55-year-old patient with Kellgren-Lawrence grade-II or III knee osteoarthritis undergoing a series of 3 PRP injections with a 1-year delay to TKA versus a TKA from the outset. Both health-care payer and societal perspectives were included. Transition probabilities were derived from systematic review of 72 studies, quality-of-life (QOL) values from the Tufts University Cost-Effectiveness Analysis Registry, and individual costs from Medicare reimbursement schedules. Primary outcome measures were total costs and quality-adjusted life years (QALYs), organized into incremental cost-effectiveness ratios (ICERs) and evaluated against willingness-to-pay thresholds of $50,000 and $100,000. One and 2-way sensitivity analyses were performed as well as a probabilistic analysis varying PRP-injection cost, TKA delay intervals, and TKA outcomes over 10,000 different simulations.
From a health-care payer perspective, PRP resulted in 14.55 QALYs compared with 14.63 for TKA from the outset, with total health-care costs of $26,619 and $26,235, respectively. TKA from the outset produced a higher number of QALYs at a lower cost, so it dominated. From a societal perspective, PRP cost $49,090 versus $49,424 for TKA from the outset. The ICER for TKA from the outset was $4,175 per QALY, below the $50,000 willingness-to-pay threshold. Assuming the $728 published cost of a PRP injection, no delay time that was <10 years produced a cost-effective course. When the QOL value was increased from the published value of 0.788 to >0.89, PRP therapy was cost-effective with even a 1-year delay to TKA.
When considering direct and unpaid indirect costs, PRP injections are not cost-effective. The primary factor preventing PRP from being cost-effective is not the price per injection but rather a lack of established clinical efficacy in relieving pain and improving function and in delaying TKA. PRP may have value for higher-risk patients with high perioperative complication rates, higher TKA revision rates, or poorer postoperative outcomes.
Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.
All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of ...chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast aging. Using a system called “ICE” (inducible changes to the epigenome), we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation. These data are consistent with the information theory of aging, which states that a loss of epigenetic information is a reversible cause of aging.
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•Cellular responses to double-stranded DNA breaks erode the epigenetic landscape•This loss of epigenetic information accelerates the hallmarks of aging•These changes are reversible by epigenetic reprogramming•By manipulating the epigenome, aging can be driven forward and backward
Aging is characterized by changes in cellular identity and function over time. This process is driven by changes in chromatin factor localization during DNA break repair, which alters the epigenome and advances the epigenetic clock. Expression of a subset of Yamanka factors, OSK, can reverse these changes and modulate aging.
Objective
To evaluate change in sedentary behavior (SB) and physical activity (PA) over 3 years following bariatric surgery.
Methods
A subset of participants in an observational study (n = 473 of ...2,458; 79% female, median body mass index 45 kg m−2) wore an activity monitor presurgery and at 1‐3 annual postsurgery assessments.
Results
Over the first year, on average, sedentary time decreased from 573 (95% CI: 563‐582) to 545 (95% CI: 534‐555) min days−1 and moderate‐ to vigorous‐intensity PA (MVPA) increased from 77 (95% CI: 71‐84) to 106 (95% CI: 98‐116) min week−1, or 7 (95% CI: 5‐10) to 24 (95% CI: 18‐29) min week−1 in MVPA bouts ≥10 min. There were no changes in these parameters from years 1 to 3 (P for all > 0.05). The percentage of participants achieving ≥150 min week−1 of bout‐related MVPA was not different at year 3 6.5% (95% CI: 3.1‐12.7) vs. presurgery 3.4% (95% CI: 1.8‐5.0); P = 0.45. Most participants followed SB and PA trajectories that paralleled mean change and were consistent with their presurgery position in relation to the group.
Conclusions
On average, bariatric surgical patients make small reductions in SB and increases in PA during the first postsurgery year, which are maintained through 3 years. Still, postsurgery PA levels fall short of PA guidelines for general health or weight control.
Platelet-rich plasma (PRP) injections are often used for the treatment of knee osteoarthritis (OA), despite clinical value and cost-effectiveness not being definitely established. PRP injections are ...considered as a potential means of reducing pain and improving function in patients with knee OA, in the hope of delaying or avoiding the need for surgical intervention. Centers that offer PRP injections usually charge patients out of pocket and directly market services. Therefore, the purpose of this study was to quantify the current (1) prices and (2) marketed clinical efficacy of autologous PRP injections for knee OA. A prospective cross-sectional study was performed based on 286 centers identified in the United States offering PRP injections for knee OA. A total of 179 (73.4%) centers were successfully contacted via e-mail or phone, using a simulated 52-year-old male patient with knee OA. Scripted questions were asked by the simulated patient to determine the current marketed prices and clinical efficacy, either reported as "good results" or "symptomatic improvement," claimed by each treating center. The mean price for a single unilateral knee same-day PRP injection was $714 with a standard deviation of $144 (95% confidence interval CI: $691-737,
= 153). The mean claim of clinical efficacy was 76% with a standard deviation of 11% (95% CI: 73.5-78.3%,
= 84). Out of the 84 clinics, 10 claimed "90 to 100% efficacy," 27 claimed "80 to 90%," 29 claimed "70 to 80%," 9 claimed "60 to 70%," 8 claimed "50 to 60%," and 1 claimed "40 to 60%." These findings provide a unique perspective on the PRP market for the treatment of knee OA that is valuable to physicians and health care providers in providing better education to patients on the associated costs and purported clinical benefits of PRP injections.
Long-term outcomes after face transplantation are rarely reported in the scientific literature. Here we present outcome data of a partial face allograft recipient 10 years after transplantation.
...Medical records were reviewed for functional and psychosocial outcomes as well as complications. Histopathologic analyses of autopsy tissues and characterization of skin immune cells were performed.
The patient retained long-term motor and sensory function, though with a noticeable drop in sensory function after year 5. Social reintegration of the patient was marked by reconnection with his family and participation in public social activities. Immunosuppressive therapy consisted of tacrolimus (target levels 6–8 ng/mL after the first year), mycophenolate, and prednisone, while steroids were completely weaned between years 1 and 7. One acute cellular rejection episode of grade II or higher occurred on average per year and led to chronic skin changes (papillary dermal sclerosis with superficial hyalinization, epidermal thinning with loss of rete ridges, perieccrine fibrosis), but the allograft vessels, muscles, adipose tissue, and bone were spared. Allograft skin was characterized by increased number of CD4+ TNF-α/IL17A producing T-cells as compared with native skin. Long-term kidney function was maintained at 60 mL/min estimated glomerular filtration rate. Unfortunately, the preexisting hepatitis C virus infection with liver cirrhosis was resistant to 3 treatments with new direct-acting antivirals and eventually hepatocellular carcinoma developed, causing the patient’s death 10 years after transplantation.
This report suggests that face transplants can maintain their function for at least 10 years. Chronic skin changes can occur independently of allograft vasculopathy.
To evaluate whether augmenting traditional fixation with a femoral neck buttress plate (FNBP) improves clinical outcomes in young adults with high-energy displaced femoral neck fractures.
Multicenter ...retrospective matched cohort comparative clinical study.
Twenty-seven North American Level 1 trauma centers.
Adult patients younger than 55 years who sustained a high-energy (nonpathologic) displaced femoral neck fracture.
Operative reduction and stabilization of a displaced femoral neck fracture with (group 1) and without (group 2) an FNBP.
Complications including failed fixation, nonunion, osteonecrosis, malunion, and need for subsequent major reconstructive surgery (early revision of reduction and/or fixation), proximal femoral osteotomy, or arthroplasty.
Of 478 patients younger than 55 years treated operatively for a displaced femoral neck fracture, 11% (n = 51) had the definitive fixation augmented with an FNBP. One or more forms of treatment failure occurred in 29% (n = 15/51) for group 1 and 49% (209/427) for group 2 ( P < 0.01). When FNBP fixation was used, mini-fragment (2.4/2.7 mm) fixation failed significantly more often than small-fragment (3.5 mm) fixation (42% vs. 5%, P < 0.01). Irrespective of plate size, anterior and anteromedial plates failed significantly more often than direct medial plates (75% and 33% vs. 9%, P < 0.001).
The use of a femoral neck buttress plate to augment traditional fixation in displaced femoral neck fractures is associated with improved clinical outcomes, including lower rates of failed fixation, nonunion, osteonecrosis, and need for secondary reconstructive surgery. The benefits of this technique are optimized when a small-fragment (3.5 mm) plate is applied directly to the medial aspect of the femoral neck, avoiding more anterior positioning .
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
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