Anteromedial knee osteoarthritis (AMOA) evaluated with magnetic resonance imaging (MRI): a cohort study of 100 patients.

INTRODUCTION: Magnetic resonance imaging (MRI) scans are increasingly used for knee osteoarthritis evaluation and preoperative planning before unicompartmental knee arthroplasty (UKA), and often patients already have MRI scans before their initial surgeon consultation. This highlights the need for surgeons to understand anteromedial osteoarthritis (AMOA) patterns on MRI. Hence, we aim to describe MRI findings in patients with AMOA meeting current indications for medial UKA. MATERIALS AND METHODS: We analysed MRI scans from 100 knees evaluated for UKA between 2006 and 2013. Inclusion criteria comprised full-thickness medial compartment loss and intact lateral compartment joint space on preoperative radiographs. Assessment included cartilage lesions, osteophytes, meniscal damage, and anterior-cruciate ligament (ACL) status on tibial and femoral surfaces. Final decision to proceed with UKA relied on intraoperative findings, independent of MRI. RESULTS: Complete anteromedial tibial and femoral cartilage loss preserved posterior cartilage rims was evident in all cases. Cartilage thinning occurred in the lateral compartment in 34% of cases. While 62% displayed lateral osteophytes, only 6 exhibited small areas of full-thickness cartilage loss. ACL abnormalities varied: 27% normal, 3% ruptured, and 70% had intrasubstance high signal. Larger osteophytes in the medial (p = 0.012) and lateral (p = 0.002) intercondylar notch correlated significantly with ACL damage. All underwent medial UKA, with no evidence of areas with full lateral compartment cartilage loss intraoperatively. CONCLUSIONS: The MRI findings confirmed the radiographic diagnosis of bone-on-bone medial disease but highlights a range of findings in the ACL, lateral compartment, and patellofemoral joint compartment for patients who met the current x-ray and intraoperative indication for UKA. Further research is required to understand if these MRI changes will affect long-term outcomes.

International Multicenter Validation of an Intermediate Risk Subclassification of Prostate Cancer Managed with Radical Treatment without Hormone Therapy.

PURPOSE: The NCCN Guidelines® recently endorsed a subclassification of intermediate risk prostate cancer into favorable and unfavorable subgroups. However, this subclassification was developed in a treatment heterogeneous cohort. Thus, to our knowledge the natural history of androgen deprivation treatment naïve favorable and unfavorable intermediate risk prostate cancer cases remains unknown. MATERIALS AND METHODS: Groups at 3 academic centers pooled data on patients with intermediate risk prostate cancer treated with radical monotherapy (dose escalated external beam radiotherapy, brachytherapy or radical prostatectomy) without combined androgen deprivation treatment. We used the cumulative incidence with competing risk analysis to estimate biochemical recurrence, distant metastasis and prostate cancer specific mortality. RESULTS: A total of 2,550 men at intermediate risk were included in study, of whom 1,063 and 1,487 were at favorable and unfavorable risk, respectively. Of the men 1,149 underwent radical prostatectomy, 1,143 underwent dose escalated external beam radiotherapy and 258 underwent brachytherapy. Median followup after the different treatments ranged from 60.4 to 107.4 months. The 10-year cumulative incidence of distant metastasis in the favorable vs unfavorable risk groups was 0.2% (95% CI 0.2-0.2) vs 11.6% (95% CI 7.7-15.5) for radical prostatectomy (p <0.001), 2.8% (95% CI 0.8-4.8) vs 13.5% (95% CI 9.6-17.4) for dose escalated external beam radiotherapy (p <0.001) and 3.5% (95% CI 0-7.4) vs 10.2% (95% CI 4.3-16.1) for brachytherapy (p = 0.063). The 10-year rate of prostate cancer specific mortality in the favorable vs unfavorable risk groups was 0% (95% CI 0-0) vs 3.7% (95% CI 1.7-5.7) for radical prostatectomy (p = 0.016), 0.5% (95% CI 0.5-0.5) vs 5.6% (95% CI 3.6-7.6) for dose escalated external beam radiotherapy (p = 0.015) and 0% (95% CI 0-0) vs 2.5% (95% CI 0.5-4.5) for brachytherapy (p = 0.028). CONCLUSIONS: This multicenter international effort independently validates the prognostic value of the intermediate risk prostate cancer subclassification in androgen deprivation treatment naïve cases across all radical treatment modalities. It is unlikely that treatment intensification would meaningfully improve oncologic outcomes in men at favorable intermediate risk.

The effect of chronic renal insufficiency by use of glomerular filtration rate versus serum creatinine level on late clinical outcome of carotid endarterectomy.

BACKGROUND: Several studies have reported mixed results after carotid endarterectomy (CEA) in patients with chronic renal insufficiency (CRI), and we previously reported the perioperative outcome in patients with CRI by use of serum creatinine (Cr) level and glomerular filtration rate (GFR). However, only a few of these studies used GFR by the Modification of Diet in Renal Disease equation in their analysis of long-term outcome. METHODS: During the study period, 1000 CEAs (926 patients) were analyzed; 940 of these CEAs had Cr levels and 925 had GFR data. Patients were classified into normal (GFR ≥60 mL/min/1.73 m(2) or Cr <1.5 mg/dL), moderate CRI (GFR ≥30-59 or Cr ≥1.5-2.9), and severe CRI (GFR <30 or Cr ≥3). RESULTS: At a mean follow-up of 34.5 months and a median of 34 months (range, 1-53 months), combined stroke and death rates for Cr levels (867 patients) were 9%, 18%, and 44% for Cr <1.5, ≥1.5 to 2.9, and ≥3 (P = .0001) in contrast to 8%, 14%, and 26% for GFR (854 patients) of >60, ≥30 to 59, and <30, respectively (P = .0003). Combined stroke and death rates for asymptomatic patients were 8%, 17%, and 44% (P = .0001) for patients with Cr levels of <1.5, ≥1.5 to 2.9, and ≥3, respectively, vs 7%, 13%, and 24% for a GFR of ≥60, ≥30 to 59, and <30 (P = .0063). By Kaplan-Meier analysis, stroke-free survival rates at 1 year, 2 years, and 3 years were 97%, 94%, and 92% for Cr <1.5; 92%, 85%, and 81% for Cr ≥1.5 to 2.9; and 56%, 56%, and 56% for Cr ≥3 (P < .0001); vs 98%, 95%, and 93% for a GFR ≥60; 93%, 90%, and 86% for a GFR of ≥30 to 59; and 86%, 77%, and 73% for a GFR <30 (P < .0001). These rates for asymptomatic patients at 1 year, 2 years, and 3 years were 97%, 95%, and 93% for Cr <1.5; 94%, 87%, and 82% for Cr ≥1.5 to 2.9; and 56%, 56%, and 56% for Cr ≥3 (P < .0001); vs 98%, 95%, and 94% for a GFR ≥60; 95%, 91%, and 86% for a GFR of ≥30 to 59; and 84%, 80%, and 75% for a GFR <30 (P = .0026). A univariate regression analysis for asymptomatic patients showed that the hazard ratio (HR) of stroke and death was 6.5 (P = .0003) for a Cr ≥3 and 3.1 for a GFR <30 (P = .0089). A multivariate analysis showed that Cr ≥3 had an HR of stroke and death of 4.7 (P = .008), and GFR <30 had an HR of 2.2 (P = .097). CONCLUSIONS: Patients with severe CRI had higher rates of combined stroke/death. Therefore, CEA for these patients (particularly in asymptomatic patients) must be considered with caution.

The value and economic analysis of routine postoperative carotid duplex ultrasound surveillance after carotid endarterectomy.

BACKGROUND: Several studies have reported on the role of postoperative duplex ultrasound surveillance after carotid endarterectomy (CEA) with varying results. Most of these studies had a small sample size or did not analyze cost-effectiveness. METHODS: We analyzed 489 of 501 CEA patients with patch closure. All patients had immediate postoperative duplex ultrasound examination and were routinely followed up both clinically and with duplex ultrasound at regular intervals of 1 month, 6 months, 12 months, and every 12 months thereafter. A Kaplan-Meier analysis was used to estimate the rate of ≥50% and ≥80% post-CEA restenosis over time and the time frame of progression from normal to ≥50% or ≥80% restenosis. The cost of post-CEA duplex surveillance was also estimated. RESULTS: Overall, 489 patients with a mean age of 68.5 years were analyzed. Ten of these had residual postoperative ≥50% stenosis, and 37 did not undergo a second duplex ultrasound examination and therefore were not included in the final analysis. The mean follow-up was 20.4 months (range, 1-63 months), with a mean number of duplex ultrasound examinations of 3.6 (range, 1-7). Eleven of 397 patients (2.8%) with a normal finding on immediate postoperative duplex ultrasound vs 4 of 45 (8.9%) with mild stenosis on immediate postoperative duplex ultrasound progressed to ≥50% restenosis (P = .055). Overall, 15 patients (3.1%) had ≥50% restenosis, 9 with 50% to <80% and 4 with 80% to 99% (2 of these had carotid artery stenting reintervention), and 2 had late carotid occlusion. All of these were asymptomatic, except for one who had a transient ischemic attack. The mean time to ≥50% to <80% restenosis was 14.7 months vs 19.8 months for ≥80% restenosis after the CEA. Freedom from restenosis rates were 98%, 96%, 94%, 94%, and 94% for ≥50% restenosis and 99%, 98%, 97%, 97%, and 97% for ≥80% restenosis at 1 year, 2 years, 3 years, 4 years, and 5 years, respectively. Freedom from myocardial infarction, stroke, and deaths was not significantly different between patients with and without restenosis (100%, 93%, 83%, and 83% vs 94%, 91%, 86%, and 79% at 1 year, 2 years, 3 years, and 4 years, respectively; P = .951). The estimated charge of this surveillance was 3.6 × 489 (number of CEAs) × $800 (charge for carotid duplex ultrasound), which equals $1,408,320, to detect only four patients with ≥80% to 99% restenosis who may have been potential candidates for reintervention. CONCLUSIONS: This study shows that the value of routine postoperative duplex ultrasound surveillance after CEA with patch closure may be limited, particularly if the finding on immediate postoperative duplex ultrasound is normal or shows minimal disease.

Bad blood: poverty, psychopathy and the politics of transgression in Kenya Colony, 1939-59.

This article examines the inter-relationship between psychiatry and sex, both fertile fields within the recent historiography of colonialism and empire. Using a series of case files pertaining to European patients admitted to the Mathari Mental Hospital in Nairobi during the 1940s and 1950s, this article shows how sexual transgression among colonial Europeans precipitated, and was combined with, mental distress. Considering psychiatric treatment as a form of social control, the article investigates a number of cases in which a European patient had been perceived to have transgressed the normative sexual behaviour codes of settler society in Kenya. What these files suggest is that transgressive sexuality in Kenya was itself framed by indices, as insistent as they were uncertain, of gender, race and class. While psychiatry as social control has some degree of purchase here, more valuable is an attempt to discern the particular ways in which certain forms of sexual behaviour were understood in diagnostic terms. Men who had sex with Africans, we see, tended to be diagnosed as 'depressed' on arrival at the hospital but were judged to be mentally normal consequently. Women, by contrast, were liable to be diagnosed as psychopathic, a diagnosis, I argue, that helped to explain the uniquely transgressive status of impoverished European women living alone in the margins of white society. Unlike white men, moreover, women did not have to have sex with non-Europeans to transgress sexual codes: this is because female poverty was a sexual problem in a way that male poverty decidedly was not. Poor white women were marked by uncertainty over their sexual behaviour­and dubious racial identity in its turn­and the problem of social contamination was described by reference both to the polluted racial ancestry of an individual and to the prospective contamination of healthy racial stocks. This article aims to address current historical debates around sex and empire, 'white subalternity' and the social history of psychiatry and mental health. All names have been changed to protect patient anonymity.

Experimental and Computational Study of the Gas-Phase Acidities of Acidic Di- and Tripeptides.

Gas-phase acidities (GA or Δ Gacid) of acidic di- and tripeptides are determined for the first time. The peptides studied are composed of inert alanine (A) residues and one X residue of either aspartic acid (D) or glutamic acid (E): AX, XA, AAX, AXA, and XAA. Experimental GAs were measured by the thermokinetic method of deprotonation ion/molecule reactions in a Fourier transform ion cyclotron resonance mass spectrometer. Calculated GAs were obtained by composite correlated molecular orbital theory at the G3(MP2) level for deprotonation of carboxylic acid groups both at the C-terminus and at the side chain. Excellent agreement was found between experimental and calculated GA values. There is a slight preference for peptides with D being more acidic than analogous peptides with E, which agrees with the GAs of the corresponding amino acids. Experiments showed that peptides are more acidic (lower numerical GA values) when the acidic residue is located at the C-terminus (i.e., AX or AAX). The lowest energy form of deprotonated AAE has a unique structure where the longer side chain of E allows the two carboxylates, which are in close proximity, to share the proton. The tripeptides are less acidic (higher GA value) by 3-7 kcal/mol when the acidic residue is in the center. The tripeptides are more acidic (by 2-10 kcal/mol) than dipeptides containing the same acidic residue at the same location.

Effect of statins on early and late clinical outcomes of carotid endarterectomy and the rate of post-carotid endarterectomy restenosis.

BACKGROUND: This study analyzed the effect of statins on clinical outcomes after carotid endarterectomy (CEA) and the rate of restenosis. STUDY DESIGN: We performed a retrospective analysis of prospectively collected data on 500 consecutive CEAs followed at 1, 6, and 12 months and every year. RESULTS: There were 299 patients on statins vs 201 without. Combined perioperative MI/death rates were 2.7% vs 4% (p = 0.416) and MI/stroke/death rates were 4% vs 5% (p = 0.607) for statins vs no statins. At mean follow-up (27 months), MI, stroke, and death rates were: 9.7%, 2.3%, and 2.3% vs 9%, 2.5% and 4.5% (p = 0.18) for statins vs no statins, respectively. Diabetic patients not on statins had 4 times more deaths (8.5% vs 2.3%) and twice as many strokes/deaths (10.2% vs 5.3%). Patients with hypercholesterolemia who were not on statins had twice as many deaths (4.3% vs 2.2%). Rates of freedom from stroke/MI/death at 1, 2, 3, and 4 years were: 94%, 90%, 85% and 77% vs 94%, 89%, 85%, and 82% (p = 0.87) for statins vs no statins, respectively. Rates of freedom from death only for patients on statins vs no statins at 1, 2, 3, and 4 years were: 98%, 98%, 97.4% and 97.4% vs 98%, 96%, 94.8% and 94.8%, respectively (p = 0.191). For diabetic patients, rates of freedom from death at 1, 2, 3, and 4 years were 99%, 99%, 97%, and 97% for statins vs 97%, 90%, 90%, and 90% without statins, respectively (p = 0.048). Post-CEA restenosis rates ≥ 50% were not significantly different between statins vs no statins (p = 0.64). CONCLUSIONS: Statins significantly lowered death rates in patients with diabetes and tended to lower both death and stroke rates in diabetic patients and patients with hypercholesterolemia. Statins had no effect on post-CEA restenosis.

Targeted radiosensitization of ETS fusion-positive prostate cancer through PARP1 inhibition.

ETS gene fusions, which result in overexpression of an ETS transcription factor, are considered driving mutations in approximately half of all prostate cancers. Dysregulation of ETS transcription factors is also known to exist in Ewing's sarcoma, breast cancer, and acute lymphoblastic leukemia. We previously discovered that ERG, the predominant ETS family member in prostate cancer, interacts with the DNA damage response protein poly (ADP-ribose) polymerase 1 (PARP1) in human prostate cancer specimens. Therefore, we hypothesized that the ERG-PARP1 interaction may confer radiation resistance by increasing DNA repair efficiency and that this radio-resistance could be reversed through PARP1 inhibition. Using lentiviral approaches, we established isogenic models of ERG overexpression in PC3 and DU145 prostate cancer cell lines. In both cell lines, ERG overexpression increased clonogenic survival following radiation by 1.25 (±0.07) fold (mean ± SEM) and also resulted in increased PARP1 activity. PARP1 inhibition with olaparib preferentially radiosensitized ERG-positive cells by a factor of 1.52 (±0.03) relative to ERG-negative cells (P < .05). Neutral and alkaline COMET assays and immunofluorescence microscopy assessing γ-H2AX foci showed increased short- and long-term efficiencies of DNA repair, respectively, following radiation that was preferentially reversed by PARP1 inhibition. These findings were verified in an in vivo xenograft model. Our findings demonstrate that ERG overexpression confers radiation resistance through increased efficiency of DNA repair following radiation that can be reversed through inhibition of PARP1. These results motivate the use of PARP1 inhibitors as radiosensitizers in patients with localized ETS fusion-positive cancers.