Citations

Background: Reports have concluded that platelet-rich plasma (PRP) is an effective and safe biological approach in the treatment of knee osteoarthritis (OA). However, no consensus has been established regarding the number of injections required to observe a therapeutic effect. Purpose: To compare the clinical effectiveness reported in randomized controlled trials (RCTs) of single versus multiple PRP injections in the treatment of knee OA. Study Design: Systematic review; Level of evidence, 1. Methods: A comprehensive search was conducted for RCTs published between 1970 and 2019 that compared the effect of single versus multiple PRP injections on pain and functionality in patients with knee OA. Searched databases included MEDLINE, Scopus, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. A data extraction form was designed to obtain bibliographic information of the study as well as patient, intervention, comparison, and outcomes of interest data. A random-effects model was used to pool quantitative data from the primary outcomes. Results: We included 5 clinical trials with a low-moderate risk of bias that reported data for 301 patients. Meta-analysis showed that, at 6 months after the intervention, single and multiple (double or triple) injections had similar pain improvement, with no significant differences (standardized mean difference [SMD], 0.61 [95% CI, −1.09 to 2.31]; I 2 = 97%; P = .48). A significant improvement in knee functionality was observed in favor of multiple injections (SMD, 2.29 [95% CI, 0.45-4.12]; I 2 = 97%; P = .01). Subanalysis showed that the significant improvement was only evident for the results of single versus triple injections (SMD, 3.12 [95% CI, 0.64-5.60]; I 2 = 97%; P = .01). Conclusion: According to our results, a single injection was as effective as multiple PRP injections in pain improvement; however, multiple injections seemed more effective in joint functionality than a single injection at 6 months. We consider that the available evidence is still insufficient, and future research on this specific topic is needed to confirm our results.

AbstractIntroductionConventional Z‐scores are generated by subtracting the mean and dividing by the standard deviation. More recent methods linearly correct for age, sex, and education, so that these “adjusted” Z‐scores better represent whether an individual's cognitive performance is abnormal. Extreme negative Z‐scores for individuals relative to this normative distribution are considered indicative of cognitive deficiency.MethodsIn this article, we consider nonlinear shape constrained additive models accounting for age, sex, and education (correcting for nonlinearity). Additional shape constrained additive models account for varying standard deviation of the cognitive scores with age (correcting for heterogeneity of variance).ResultsCorrected Z‐scores based on nonlinear shape constrained additive models provide improved adjustment for age, sex, and education, as indicated by higher adjusted‐R2.DiscussionNonlinearly corrected Z‐scores with respect to age, sex, and education with age‐varying residual standard deviation allow for improved detection of non‐normative extreme cognitive scores.

AbstractChemotherapy‐induced peripheral neuropathy (henceforth, neuropathy) is often dose limiting and is generally managed by empirical dose modifications. We aimed to (1) identify an early time point that is predictive of future neuropathy using a patient‐reported outcome and (2) propose a dose‐adjustment algorithm based on simulated data to manage neuropathy. In previous work, a dose‐neuropathy model was developed using dosing and patient‐reported outcome data from Cancer and Leukemia Group B 40502 (Alliance), a randomized phase III trial of paclitaxel, nanoparticle albumin–bound paclitaxel or ixabepilone as first‐line chemotherapy for locally recurrent or metastatic breast cancer. In the current work, an early time point that is predictive of the future severity of neuropathy was identified based on predictive accuracy of the model. Using the early data and model parameters, simulations were conducted to propose a dose‐adjustment algorithm for the prospective management of neuropathy in individual patients. The end of the first 3 cycles (12 weeks) was identified as the early time point based on a predictive accuracy of 75% for the neuropathy score after 6 cycles. For paclitaxel, nanoparticle albumin–bound paclitaxel, and ixabepilone, simulations with the proposed dose‐adjustment algorithm resulted in 61%, 48%, and 35% fewer patients, respectively, with neuropathy score ≥8 after 6 cycles compared to no dose adjustment. We conclude that early patient‐reported outcome data on neuropathy can be used to guide dose adjustments in individual patients that reduce the severity of future neuropathy. Prospective validation of this approach should be undertaken in future studies.

Background: Periacetabular osteotomy (PAO) can be used for joint preservation in symptomatic developmental dysplasia of the hip (DDH) and femoroacetabular impingement (FAI). 1 of the most common procedures following PAO is hardware removal. The aims of this study were to determine the rate of hardware removal and patient characteristics associated with this outcome following PAO. Methods: Data from a prospectively-collected registry was retrospectively reviewed at one institution managing DDH or FAI patients with PAO from July 2008–December 2015. Patients who completed preoperative and postoperative patient reported outcome (PRO) questionnaires with minimum 1-year follow-up were evaluated, resulting in 221 patients followed for a mean of 2.8 years (range 1.0–7.7 years). There were 80% women, mean age was 25 years and mean body mass index (BMI) was 25 kg/m 2 . Fully-threaded 4.5-mm screws were used for internal fixation. Results: Hardware removal occurred in 30 patients (13.6%) at a mean of 1.0 years after PAO. Patients undergoing hardware removal were younger (mean age 20.4 vs. 26.3 years), thinner (mean BMI 22.2 vs. 25.1), had less severe dysplasia (DDH patients only: mean lateral centre-edge angle 21.0 vs. 16.2, mean Tönnis angle 12.9 vs. 16.8), and were more likely to have PAO for FAI (33% vs. 11%) compared to patients with retained hardware. At final follow-up, multivariable analysis demonstrated a trend toward inferior patient reported outcomes in the hardware removal group. Conclusions: This study defines the incidence and characteristics of patients undergoing hardware removal after PAO and demonstrates similar outcomes to patients who do not require hardware removal.

Purpose: To demonstrate the feasibility of a physician-modified endograft (PMEG) with inner branches for 2 mesenteric arteries as an alternative to fenestrations or directional branches. Technique: A symptomatic 60-year-old man presented with supraceliac para-anastomotic pseudoaneurysm involving an antegrade aorta to celiac artery and superior mesenteric artery bypass. Since an off-the-shelf multibranched endograft was inappropriate, a Zenith Alpha thoracic stent-graft was modified with 2 inner branches fashioned of 8-mm Viabahn endoprostheses with preloaded guidewires. The procedure was technically successful, and the patient had no postoperative complications. Conclusion: Inner branches might offer an alternative to fenestrations or directional branches in patients with narrow aortas.

Objective. Osteochondral allograft (OCA) transplantation has demonstrated good long-term outcomes in treatment of cartilage defects. Viability, a key factor in clinical success, decreases with peri-implantation storage at 4°C during pathogen testing, matching logistics, and transportation. Modern, physiologic storage conditions may improve viability and enhance outcomes. Design. Osteochondral specimens from total knee arthroplasty patients (6 males, 5 females, age 56.4 ± 2.2 years) were stored in media and incubated at normoxia (21% O 2 ) at 22°C or 37°C, and hypoxia (2% O 2 ) at 37°C. Histology, live-dead staining, and quantitative polymerase chain reaction (qPCR) was performed 24 hours after harvest and following 7 days of incubation. Tissue architecture, cell viability, and gene expression were analyzed. Results. No significant viability or gene expression deterioration of cartilage was observed 1-week postincubation at 37°C, with or without hypoxia. Baseline viable cell density (VCD) was 94.0% ± 2.7% at day 1. At day 7, VCD was 95.1% (37°C) with normoxic storage and 92.2% (37°C) with hypoxic storage ( P ≥ 0.27). Day 7 VCD (22°C) incubation was significantly lower than both the baseline and 37°C storage values (65.6%; P < 0.01). COL1A1, COL1A2, and ACAN qPCR expression was unchanged from baseline ( P < 0.05) for all storage conditions at day 7, while CD163 expression, indicative of inflammatory macrophages and monocytes, was significantly lower in the 37°C groups ( P < 0.01). Conclusion. Physiologic storage at 37°C demonstrates improved chondrocyte viability and metabolism, and maintained collagen expression compared with storage at 22°C. These novel findings guide development of a method to optimize short-term fresh OCA storage, which may lead to improved clinical results.

Objective: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0–38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×10 3 cells/μL emerged as independent predictors for thrombus formation or embolism. Conclusions: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01947621.

AbstractIntroductionThe Advancing Research and Treatment in Frontotemporal Lobar Degeneration and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects longitudinal studies were designed to describe the natural history of familial‐frontotemporal lobar degeneration due to autosomal dominant mutations.MethodsWe examined cognitive performance, behavioral ratings, and brain volumes from the first time point in 320 MAPT, GRN, and C9orf72 family members, including 102 non–mutation carriers, 103 asymptomatic carriers, 43 mildly/questionably symptomatic carriers, and 72 carriers with dementia.ResultsAsymptomatic carriers showed similar scores on all clinical measures compared with noncarriers but reduced frontal and temporal volumes. Those with mild/questionable impairment showed decreased verbal recall, fluency, and Trail Making Test performance and impaired mood and self‐monitoring. Dementia was associated with impairment in all measures. All MAPT carriers with dementia showed temporal atrophy, but otherwise, there was no single cognitive test or brain region that was abnormal in all subjects.DiscussionImaging changes appear to precede clinical changes in familial‐frontotemporal lobar degeneration, but specific early clinical and imaging changes vary across individuals.

AbstractBackgroundLocal recurrence (LR) of sacral chordoma is a difficult problem and the mortality risk associated with LR remains poorly described. The purpose of this study was to evaluate the risk of mortality in patients with LR and determine if patient age is associated with mortality.MethodsA total of 218 patients (144 male, 69 female; mean age 59 ± 15 years) with sacrococcygeal chordomas were reviewed. Cumulative incidence functions and competing risks for death due to disease and nondisease mortality were employed to analyze mortality trends following LR.ResultsThe 10‐year overall survival (OS) was 55%. Patients with LR had 44% 10‐year OS, similar to patients without (59%; P = .38). The 10‐year OS between those less than 55 compared with ≥55 years were similar (69% vs 48%; P = .52). The 10‐year death due to disease was worse in patients with LR compared with those without (44% vs 84%; P < .001). In patients without LR, patients ≥55 years were 1.6‐fold more likely to experience death due to other causes.ConclusionsPatients with an LR are more likely to die due to disease. Advanced patient age was associated with higher all‐cause mortality following resection of sacral chordoma. LR of chordoma was associated with increased disease‐specific mortality, regardless of age.