Our whole conception and acknowledgement of personality – both scientific and quotidian – is based on the notion of difference. A personality is precisely that which distinguishes one individual from ...another. These differences have consequences for behavior, health, and well-being, but we are mostly ignorant of their evolutionary roots. For humans and other primates, evidence is coalescing around a common structure that describes personality differences usefully categorizable in terms of shared versus derived traits and consistent with known species differences (Gosling and John 1999; Weiss et al.2006). Although functional and genomic studies begin to hint at the proximate genetic and environmental factors that mix to produce differences in personality, we are still left with this wondrous puzzle: Why do these basic differences persist over evolutionary time scales as primates have speciated and evolved?
Perioperative neurocognitive disorders (PND) are common complications in older adults associated with increased 1-year mortality and long-term cognitive decline. One risk factor for worsened ...long-term postoperative cognitive trajectory is the Alzheimer's disease (AD) genetic risk factor APOE4. APOE4 is thought to elevate AD risk partly by increasing neuroinflammation, which is also a theorized mechanism for PND. Yet, it is unclear whether modulating apoE4 protein signaling in older surgical patients would reduce PND risk or severity.
MARBLE is a randomized, blinded, placebo-controlled phase II sequential dose escalation trial designed to evaluate perioperative administration of an apoE mimetic peptide drug, CN-105, in older adults (age≥60 years). The primary aim is evaluating the safety of CN-105 administration, as measured by adverse event rates in CN-105 versus placebo-treated patients. Secondary aims include assessing perioperative CN-105 administration feasibility and its efficacy for reducing postoperative neuroinflammation and PND severity.
201 patients undergoing non-cardiac, non-neurological surgery will be randomized to control or CN-105 treatment groups and receive placebo or drug before and every six hours after surgery, for up to three days after surgery. Chart reviews, pre- and postoperative cognitive testing, delirium screening, and blood and CSF analyses will be performed to examine effects of CN-105 on perioperative adverse event rates, cognition, and neuroinflammation. Trial results will be disseminated by presentations at conferences and peer-reviewed publications.
MARBLE is a transdisciplinary study designed to measure CN-105 safety and efficacy for preventing PND in older adults and to provide insight into the pathogenesis of these geriatric syndromes.
What does it mean to study Paul the Apostle as Jew, Greek, and Roman? The framing of the question exposes the fact that the distinctions themselves involve a complex of ethnic, social, and cultural ...designations. Paul is both a complicated individual of the ancient world, because he combines in his one personage features of life in each of these cultural-ethnic (and even religious) areas of the ancient world, and one of many people of that world who evidenced such complexity. This volume, Paul: Jew, Greek, and Roman, explores a number of the important and diverse cultural, ethnic, and religious dimensions of the multi-faceted background of Paul the Apostle. Some of the treatments are focused and specific, while others range over the broad issues that go to making up the world of the Apostle.
Significance Colorectal cancer is a leading cause of cancer-related deaths world-wide. African Americans exhibit the highest colon cancer incidence and mortality among all ethnic groups in the United ...States. Despite this finding, there is a dearth of knowledge on the genetic mechanisms underlying colon carcinogenesis in African Americans. We thus initiated this study to characterize the mutational landscapes of African American colon cancers. We identified new genes that are significantly mutated in colon cancer and that are highly preferentially targeted for mutations in colon cancers arising in African Americans as compared with Caucasians. These findings suggest differences in routes of colon carcinogenesis between the different ethnic groups and also may have implications for the ethnicity associated differences in tumor incidence and outcome.
We used whole-exome and targeted sequencing to characterize somatic mutations in 103 colorectal cancers (CRC) from African Americans, identifying 20 new genes as significantly mutated in CRC. Resequencing 129 Caucasian derived CRCs confirmed a 15-gene set as a preferential target for mutations in African American CRCs. Two predominant genes, ephrin type A receptor 6 ( EPHA6 ) and folliculin ( FLCN ), with mutations exclusive to African American CRCs, are by genetic and biological criteria highly likely African American CRC driver genes. These previously unsuspected differences in the mutational landscapes of CRCs arising among individuals of different ethnicities have potential to impact on broader disparities in cancer behaviors.
Group B streptococcal (GBS) infection remains the most common cause of neonatal early-onset sepsis and a significant cause of late-onset sepsis among young infants. Administration of intrapartum ...antibiotic prophylaxis is the only currently available effective strategy for the prevention of perinatal GBS early-onset disease, and there is no effective approach for the prevention of late-onset disease. The American Academy of Pediatrics joins with the American College of Obstetricians and Gynecologists to reaffirm the use of universal antenatal microbiologic-based testing for the detection of maternal GBS colonization to facilitate appropriate administration of intrapartum antibiotic prophylaxis. The purpose of this clinical report is to provide neonatal clinicians with updated information regarding the epidemiology of GBS disease as well current recommendations for the evaluation of newborn infants at risk for GBS disease and for treatment of those with confirmed GBS infection. This clinical report is endorsed by the American College of Obstetricians and Gynecologists (ACOG), July 2019, and should be construed as ACOG clinical guidance.
Background:
Studies examining the clinical outcomes of revision total ankle arthroplasty (TAA) are sparse. Revision TAA surgery has become more common with availability of revision implants and ...refinement of bone-conserving primary implants. In this study, patient-reported results and clinical outcomes were analyzed for a cohort of patients who underwent both primary and revision TAA at a single high-volume institution.
Methods:
We retrospectively reviewed prospectively collected data on 29 patients with failed primary total ankle arthroplasty. Cases of isolated polyethylene exchange, infection, or extra-articular realignment procedures were excluded. Patient-reported outcome (PRO) measures and clinical results were reviewed in this longitudinal study.
Results:
Fifteen patients (51.7%) underwent revision of just the talar and polyethylene components while 13 patients (44.8%) underwent revision of all components. The most common cause was talar subsidence (51.7%). The average time to revision was 3.9 years with a follow-up of 3.2 years after revision, and 3 (10.3%) revision arthroplasties required further surgery; 2 required conversion to arthrodesis and 1 required second revision TAA. Improvements in PROs were better after primary than revision TAA.
Conclusions:
Clinical and patient-reported results of revision ankle arthroplasty after metal component failure improved significantly but never reached the improvements seen after primary ankle arthroplasty. In our series, 10.3% of revision TAAs required a second revision TAA or arthrodesis surgery.
Levels of Evidence:
Therapeutic Level III, comparative series.
Background Conversion of ankle arthrodesis to total ankle arthroplasty remains controversial. Although satisfactory outcomes have been published, not all foot and ankle surgeons performing total ...ankle arthroplasty have embraced this modality. Methods Twenty-three total ankle arthroplasties were performed in patients who had undergone a prior or an attempted ankle arthrodesis. The mean age at surgery was fifty-nine years (range, forty-one to eighty years), and the mean duration of follow-up was 33.1 months (minimum, twelve months). Indications for the procedure were symptomatic adjacent hindfoot arthritis (twelve patients) or symptomatic tibiotalar or subtalar nonunion (eleven) after tibiotalocalcaneal arthrodesis. We performed concomitant surgical procedures in eighteen ankles (78%), with the most common procedure being prophylactic malleolar fixation (70%). We prospectively evaluated clinical outcomes using the Short Form-36 (SF-36), Short Musculoskeletal Function Assessment (SMFA), and visual analog scale (VAS) for pain and assessed initial weight-bearing radiographs and those made at the most recent follow-up evaluation. Results The mean VAS pain score (and standard deviation) improved from 65.7 ± 21.8 preoperatively to 18.3 ± 17.6 at the most recent follow-up evaluation (p < 0.001), with five patients being pain-free (VAS score = 0). The mean SMFA bother and function indexes improved from 55 ± 22.9 and 46.7 ± 12.6 preoperatively to 30.6 ± 22.7 and 25.4 ± 17.4 at the most recent follow-up visit (p = 0.001 and p < 0.001, respectively). The mean SF-36 total score improved from 37.7 ± 19.3 to 56.4 ± 23.1 (p = 0.002). The implant survival rate was 87%. Four (20%) of the tibial components and fourteen (70%) of the talar components that were not revised exhibited initial settling and then were seen to be stabilized radiographically without further change in implant position. Three total ankle replacements (13%) showed progressive talar subsidence, prompting revision. Ten patients (43%) had minor complications not requiring repeat surgery. Conclusions Short-term follow-up after conversion of ankle arthrodesis to total ankle arthroplasty demonstrated pain relief and improved function in a majority of patients. Patients who undergo this surgery frequently require concomitant procedures; we recommend prophylactic malleolar fixation when performing conversion total ankle arthroplasty. The rate of complications, particularly talar component settling and migration, is cause for concern. We do not recommend the procedure for ankle arthrodeses that included distal fibulectomy. Level of Evidence Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.
Background:
Outcomes of total ankle replacement for the treatment of end-stage ankle arthritis continue to improve. Debate continues whether a mobile-bearing total ankle replacement (MB-TAR) or a ...fixed-bearing total ankle replacement (FB-TAR) is superior, with successful outcomes reported long term for MB-TAR and at intermediate- to long-term follow-up for newer generation FB-TAR. Although comparisons between the 2 total ankle designs have been reported, to our knowledge, no investigation has compared the 2 designs with a high level of evidence. This prospective, randomized controlled trial conducted at a single institution compares patient satisfaction, functional outcomes, and radiographic results of the mobile-bearing STAR and the fixed-bearing Salto-Talaris in the treatment of end-stage ankle arthritis.
Methods:
Between November 2011 and November 2014, adult patients with end-stage ankle osteoarthritis failing nonoperative treatment were introduced to the study. With informed consent, 100 patients (31 male and 69 female, average age 65 years, range 35-85 years) were enrolled; a demographic comparison between the 2 cohorts was similar. Exclusion criteria included inflammatory arthropathy, neuropathy, weight exceeding 250 pounds, radiographic coronal plane deformity greater than 15 degrees, or extensive talar dome wear pattern (“flat-top talus”). Prospective patient-reported outcomes, physical examination, and standardized weightbearing ankle radiographs were obtained preoperatively, at 6 and 12 months postoperatively, and then at yearly intervals. Data collection included visual analog pain score, Short Form 36, Foot and Ankle Disability Index, Short Musculoskeletal Functional Assessment, and American Orthopaedic Foot & Ankle Society ankle-hindfoot score. Surgeries were performed by a nondesign team of orthopedic foot and ankle specialists with total ankle replacement expertise. Statistical analysis was performed by a qualified statistician. At average follow-up of 4.5 years (range, 2-6 years) complete clinical data and radiographs were available for 84 patients; 7 had incomplete data, 1 had died, 4 were withdrawn after enrolling but prior to surgery, and 4 were lost to follow-up.
Results:
In all outcome measures, the entire cohort demonstrated statistically significant improvements from preoperative evaluation to most recent follow-up with no statistically significant difference between the 2 groups. Radiographically, tibial lucency/cyst formation was 26.8% and 20.9% for MB-TAR and FB-TAR, respectively. Tibial settling/subsidence occurred in 7.3% of MB-TAR. Talar lucency/cyst formation occurred in 24.3% and 2.0% of MB-TAR and FB-TAR, respectively. Talar subsidence was observed in 21.9% and 2.0% of MB-TAR and FH-TAR, respectively. Reoperations were performed in 8 MB-TARs and 3 FH-TARs, with the majority of procedures being to relieve impingement or treat cysts and not to revise or remove metal implants.
Conclusion:
With a high level of evidence, our study found that patient-reported and clinical outcomes were favorable for both designs and that there was no significant difference in clinical improvement between the 2 implants. The incidence of lucency/cyst formation was similar for MB-TAR and FH-TAR for the tibial component, but the MB-TAR had greater talar lucency/cyst formation and tibial and talar subsidence. As has been suggested in previous studies, clinical outcomes do not necessarily correlate with radiographic findings. Reoperations were more common for MB-TAR and, in most cases, were to relieve impingement or treat cysts rather than revise or remove metal implants.
Level of Evidence:
Level I, prospective randomized study.
Background:
End-stage ankle arthritis is a debilitating condition often necessitating total ankle replacement (TAR). Tendo-Achilles lengthening (TAL) and gastrocnemius recession (GR) are commonly ...performed with TAR to improve ankle dorsiflexion (DF). No studies to date have radiographically analyzed tibiopedal motion to guide surgical management. The purpose of this study is to determine the effect of a TAL or GR during TAR on radiographic tibiopedal range of motion (ROM).
Methods:
A retrospective review of a prospectively maintained database was conducted followed by a propensity score–matched analysis of 110 patients who underwent TAL (n = 26), GR (n = 29), or no lengthening procedure (n = 55) with TAR. Minimum of 1-year ROM radiographic follow-up was required. Exclusion criteria included (1) calcaneal osteotomies, (2) simultaneous or previous hindfoot or midfoot arthrodesis, (3) prior ankle arthrodesis, or (4) revision TAR. Demographic data were extracted from the TAR database. Radiographic assessment included tibiopedal dorsiflexion (DF) and plantarflexion (PF).
Results:
DF improved by 2.8 degrees (P = .0286) and by 6.0 degrees (P < .0001) in the TAL and GR cohorts, respectively, with no difference in the control group (+0.7 degrees, P = .3764). PF was decreased by 4.5 degrees (P = .0152) and by 7.2 degrees (P = .0002) in the TAL and GR cohorts, respectively, with no difference in the control group (–0.2 degrees, P = .8546). Minimal differences were observed for total arc of motion for all 3 groups (control 0.5 degrees, GR –1.2 degrees, TAL –1.7 degrees), all of which were nonsignificant (all P > .05). There was no between-group difference in the change in overall arc of motion between the groups (P = .3599). GR resulted in a greater increase in DF (6.0 vs 2.8 degrees; P = .1074), with a reciprocal greater decrease in PF (7.2 vs 4.5 degrees; P = .2416) compared with the TAL cohort.
Conclusion:
Both TAL and GR increased postoperative DF; however, this was accompanied by a reciprocal loss in PF. Minimal differences were observed for total arc of motion. Patients should be counseled that concomitant procedures performed to increase DF will do so at the expense of PF.
Level of Evidence:
Level III, retrospective review of prospectively collected data.
PDF
