BACKGROUND:There is controversy about optimal limb alignment following knee replacement. An aim of using Oxford medial unicompartmental knee replacement (UKR) implants is to accurately restore normal ...ligament tension in the knee, thereby restoring normal kinematics. This return to normal tension typically results in a return to prearthritic alignment, which is frequently varus. The aim of this study was to investigate the relationship between postoperative limb alignment and postoperative patient-reported outcome and implant revision rate.
METHODS:We used a consecutive cohort of 891 knees with cemented Oxford medial UKR implants with a mean 10-year follow-up and recorded alignment. We grouped knees according to postoperative mechanical alignment as marked varus (estimated at 10°), mild varus (estimated at 5°), neutral, and valgus. The mean Oxford Knee Score (OKS) was calculated at 5 and 10 years postoperatively. Revision risk was assessed by survival analysis and component-time incidence rates.
RESULTS:Postoperatively, 67 (8%) of the 891 knees were in marked varus; 308 (35%), in mild varus; 508 (57%), in neutral; and 8 (1%), in valgus. The valgus group (8 knees) was too small for further analysis. The mean OKS (and standard deviation SD) at 10 years postoperatively was 41.7 ± 7 for marked varus, 40.5 ± 8 for mild varus, and 39.4 ± 9 for neutral alignment (p = 0.28). At 10 years, 92%, 85%, and 76% achieved a good or excellent OKS outcome, respectively (p = 0.02). Twelve-year survival rates were 93.3% for marked varus, 93.2% for mild varus, and 93.6% for neutral alignment, respectively (p = 0.53). Revision incidence rates per 100 component-years were 0.49 (95% confidence interval CI, 0.2 to 1.5), 0.36 (95% CI, 0.2 to 0.7), and 0.54 (95% CI, 0.4 to 0.8), respectively, and were not significantly different (p = 0.53).
CONCLUSIONS:Marked postoperative varus mechanical alignment of an estimated 10° was present in 8%, and mild varus of about 5° was present in 35%. Increasing varus alignment was associated with an increasing percentage of good or excellent OKS outcomes, but otherwise there were no significant differences between alignment groups in patient-reported outcome or revision rate. These data support the standard operative technique for the Oxford UKR, which aims to restore ligament tension and therefore prearthritic alignment rather than neutral mechanical alignment.
LEVEL OF EVIDENCE:Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Alcohol intake is a strong and well established risk factor for oesophageal squamous cell carcinoma (OSCC), but the association with oesophageal adenocarcinoma (OA) or adjacent tumours of the ...oesophagogastric junction (OGJA), remains unclear. Therefore, the association of alcohol intake with OSCC, OA, and OGJA was determined in nine case-control studies and two cohort studies of the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium (BEACON).
Information was collected on alcohol intake, age, sex, education, body mass index, gastro-oesophageal reflux, and tobacco smoking from each study. Along with 10,854 controls, 1821 OA, and 1837 OGJA, seven studies also collected OSCC cases (n=1016). Study specific ORs and 95% CIs were calculated from multivariate adjusted logistic regression models for alcohol intake in categories compared to non-drinkers. Summary risk estimates were obtained by random effects models. Results No increase was observed in the risk of OA or OGJA for increasing levels of any of the alcohol intake measures examined. ORs for the highest frequency category (≥ 7 drinks per day) were 0.97 (95% CI 0.68 to 1.36) for OA and 0.77 (95% CI = 0.54 to 1.10) for OGJA. Suggestive findings linked moderate intake (eg, 0.5 to <1 drink per day) to decreased risk of OA (OR 0.63, 95% CI 0.41 to 0.99) and OGJA (OR 0.78, 95% CI 0.62 to 0.99). In contrast, alcohol intake was strongly associated with increased risk of OSCC (OR for ≥ 7 drinks per day 9.62, 95% CI 4.26 to 21.71).
In contrast to OSCC, higher alcohol consumption was not associated with increased risk of either OA or OGJA. The apparent inverse association observed with moderate alcohol intake should be evaluated in future prospective studies.
Background
Evaluating the impact of steroid or immunosuppressants (SI) therapy prior to colectomy in Crohn’s disease (CD) patients on postoperative septic and colectomy-specific outcomes using the ...American College of Surgeons (ACS)–National Surgical Quality Improvement Program (NSQIP)-targeted colectomy database.
Methods
All CD patients undergoing colectomy were retrieved from the 2012–2013 NSQIP-targeted database. Thirty-day postoperative outcomes were compared for patients who were on steroids or immunosuppressants (SI) within the 30 days prior to colectomy to the others using univariable and multivariable analyses.
Results
Of 2208 CD patients, 1387 (63%) were on SI. Patients in the SI group were younger, and a greater proportion underwent laparoscopic surgery (
p
< 0.05). SI use was associated with a higher rate of sepsis (7.6 vs. 5.2%), anastomotic leak (5.6 vs. 3.5%), and return to operating room (6.8 vs. 3.3%). On multivariable analysis, SI was associated with sepsis, septic shock, and anastomotic leak odds ratio = 1.58, 95% confidence interval 1.09–2.27.
Conclusions
These results suggest that SI use within 30 days of colectomy is associated with a higher rate of sepsis and septic shock and anastomotic leak in CD patients. Withholding SI prior to surgery, or the selective use of an ostomy to mitigate the consequences of a leak and hence sepsis need due consideration prior to surgery.
Mesenchymal cells expressing platelet-derived growth factor receptor beta (PDGFRβ) are known to be important in fibrosis of organs such as the liver and kidney. Here we show that PDGFRβ
cells ...contribute to skeletal muscle and cardiac fibrosis via a mechanism that depends on αv integrins. Mice in which αv integrin is depleted in PDGFRβ
cells are protected from cardiotoxin and laceration-induced skeletal muscle fibrosis and angiotensin II-induced cardiac fibrosis. In addition, a small-molecule inhibitor of αv integrins attenuates fibrosis, even when pre-established, in both skeletal and cardiac muscle, and improves skeletal muscle function. αv integrin blockade also reduces TGFβ activation in primary human skeletal muscle and cardiac PDGFRβ
cells, suggesting that αv integrin inhibitors may be effective for the treatment and prevention of a broad range of muscle fibroses.
Cognitive decline is a feared aspect of growing old. It is a major contributor to lower quality of life and loss of independence in old age. We investigated the genetic contribution to individual ...differences in nonpathological cognitive ageing in five cohorts of older adults. We undertook a genome-wide association analysis using 549 692 single-nucleotide polymorphisms (SNPs) in 3511 unrelated adults in the Cognitive Ageing Genetics in England and Scotland (CAGES) project. These individuals have detailed longitudinal cognitive data from which phenotypes measuring each individual's cognitive changes were constructed. One SNP--rs2075650, located in TOMM40 (translocase of the outer mitochondrial membrane 40 homolog)--had a genome-wide significant association with cognitive ageing (P=2.5 × 10(-8)). This result was replicated in a meta-analysis of three independent Swedish cohorts (P=2.41 × 10(-6)). An Apolipoprotein E (APOE) haplotype (adjacent to TOMM40), previously associated with cognitive ageing, had a significant effect on cognitive ageing in the CAGES sample (P=2.18 × 10(-8); females, P=1.66 × 10(-11); males, P=0.01). Fine SNP mapping of the TOMM40/APOE region identified both APOE (rs429358; P=3.66 × 10(-11)) and TOMM40 (rs11556505; P=2.45 × 10(-8)) as loci that were associated with cognitive ageing. Imputation and conditional analyses in the discovery and replication cohorts strongly suggest that this effect is due to APOE (rs429358). Functional genomic analysis indicated that SNPs in the TOMM40/APOE region have a functional, regulatory non-protein-coding effect. The APOE region is significantly associated with nonpathological cognitive ageing. The identity and mechanism of one or multiple causal variants remain unclear.
Recent studies indicate that brain-derived neurotrophic factor (BDNF) may be implicated in the clinical action of antidepressant drugs. Repeated (2–3 weeks) administration of antidepressant drugs ...increases BDNF gene expression. The onset of this response as well as concomitant effects on the corresponding BDNF protein is however, unclear. The present study investigated the effects of acute and chronic administration of the selective serotonin reuptake inhibitor, fluoxetine (10
mg/kg p.o.), upon regional rat brain levels of BDNF mRNA and protein expression. To improve the clinical significance of the study, fluoxetine was administered orally and mRNA and protein levels were determined ex vivo using the techniques of
in situ hybridisation histochemistry and immunocytochemistry respectively. Direct measurement of BDNF protein was also carried out using enzyme-linked immunosorbent assay (ELISA).
Four days of once daily oral administration of fluoxetine induced decreases in BDNF mRNA (hippocampus, medial habenular and paraventricular thalamic nuclei). Whilst 7 days of treatment showed a non-significant increase in BDNF mRNA, there were marked and region-specific increases following 14 days of treatment. BDNF protein levels remained unaltered until 21 days of fluoxetine treatment, when the numbers of BDNF immunoreactive cells were increased, reaching significance in the pyramidal cell layer of CA1 and CA3 regions of Ammon's horn (CA1 and CA3) but not in the other sub-regions of the hippocampus. Indicative of the highly regional change within the hippocampus, the ELISA method failed to demonstrate significant up-regulation at 21 days, measuring levels of BDNF protein in the whole hippocampus. In contrast to the detected time dependent and biphasic response of the BDNF gene, activity-regulated, cytoskeletal-associated protein (
Arc) mRNA showed a gradual increase during the 14-day course of treatment.
The results presented here show that BDNF is expressed differentially depending on length of fluoxetine administration, which could contribute in explaining the slow onset of antidepressant activity observed with selective serotonin reuptake inhibitors.
Purpose
The aim of this study was to evaluate clinical outcome, failures, implant survival, and complications encountered with cementless fixation in unicompartmental knee arthroplasty (UKA).
Methods
...A systematic review of the literature on cementless fixation in UKA was performed according to the PRISMA guidelines. The following database was comprehensively searched: PubMed, Cochrane, Medline, CINAHL, Embase, and Google Scholar. The keywords “unicompartmental”, “unicondylar”, “partial knee arthroplasty”, and “UKA” were combined with each of the keyword “uncemented”, “cementless” and “survival”, “complications”, and “outcome”. The following data were extracted: demographics, clinical outcome, details of failures and revisions, cumulative survival, and complications encountered. The risk of bias of each study was estimated with the MINORS score and a further scoring system based on the presence of the primary outcomes.
Results
From a cohort of 63 studies identified using the above methodology, 10 papers (1199 knees) were included in the final review. The mean follow-up ranged from 2 to 11 years (median 5 years). The 5-year survival ranged from 90 to 99 % and the 10-year survival from 92 to 97 %. There were 48 revisions with an overall revision rate of 0.8 per 100 observed component-years. The most common cause of failure was progression of osteoarthritis in the retained compartment (0.9 %). The cumulative incidence of complications and revisions was comparable to that reported in similar studies on cemented UKAs. The advantages of cementless fixation include faster surgical time, avoidance of cementation errors, and lower incidence of radiolucent lines.
Conclusions
Cementless fixation is a safe and effective alternative to cementation in medial UKA. Clinical outcome, failures, reoperation rate, and survival are similar to those reported for cemented implants with lower incidence of radiolucent lines.
Level of evidence
IV.
Background. We describe antifungal therapy and management of complications due to Cryptococcus gattii infection in 86 Australian patients followed for at least 12 months. Methods. Patient data from ...culture-confirmed cases (2000–2007) were recorded at diagnosis, 6 weeks, 6 months, and 12 months. Clinical, laboratory, and treatment variables associated with raised intracranial pressure (ICP) and immune reconstitution inflammatory syndrome (IRIS) were determined. Results. Seven of 10 patients with lung infection received amphotericin B (AMB) induction therapy (6 with 5-flucytosine 5-FC for a median of 2 weeks); median duration of therapy including azole eradication therapy was 41 weeks, with a complete/partial clinical response in 78%. For neurologic disease, 88% of patients received AMB, 78% with 5-FC, for a median of 6 weeks. The median total course was 18 months. Nine patients receiving fluconazole induction therapy were reinduced with AMB plus 5-FC for clinical failure. Raised ICP (31 patients) was associated with initial abnormal neurology, and neurologic sequelae and/or death at 12 months (both P = .02); cerebrospinal fluid drains/shunts were placed in 58% of patients and in 64% of 22 patients with hydrocephalus. IRIS developed 2–12 months after starting antifungals in 8 patients, who presented with new/enlarging brain lesions. Risk factors included female sex, brain involvement at presentation, and higher median CD4 counts (all P < .05); corticosteroids reduced cryptococcoma-associated edema. Conclusions. Induction AMB plus 5-FC is indicated for C. gattii neurologic cryptococcosis (6 weeks) and when localized to lung (2 weeks). Shunting was often required to control raised ICP. IRIS presents with cerebral manifestations.
Objective
To assess whether women with a genetic predisposition to medical conditions known to increase pre‐eclampsia risk have an increased risk of pre‐eclampsia in pregnancy.
Design
Case–control ...study.
Setting and population
Pre‐eclampsia cases (n = 498) and controls (n = 1864) in women of European ancestry from five US sites genotyped on a cardiovascular gene‐centric array.
Methods
Significant single‐nucleotide polymorphisms (SNPs) from 21 traits in seven disease categories (cardiovascular, inflammatory/autoimmune, insulin resistance, liver, obesity, renal and thrombophilia) with published genome‐wide association studies (GWAS) were used to create a genetic instrument for each trait. Multivariable logistic regression was used to test the association of each continuous scaled genetic instrument with pre‐eclampsia. Odds of pre‐eclampsia were compared across quartiles of the genetic instrument and evaluated for significance.
Main outcome measures
Genetic predisposition to medical conditions and relationship with pre‐eclampsia.
Results
An increasing burden of risk alleles for elevated diastolic blood pressure (DBP) and increased body mass index (BMI) were associated with an increased risk of pre‐eclampsia (DBP, overall OR 1.11, 95% CI 1.01–1.21, P = 0.025; BMI, OR 1.10, 95% CI 1.00–1.20, P = 0.042), whereas alleles associated with elevated alkaline phosphatase (ALP) were protective (OR 0.89, 95% CI 0.82–0.97, P = 0.008), driven primarily by pleiotropic effects of variants in the FADS gene region. The effect of DBP genetic loci was even greater in early‐onset pre‐eclampsia cases (at <34 weeks of gestation, OR 1.30, 95% CI 1.08–1.56, P = 0.005). For other traits, there was no evidence of an association.
Conclusions
These results suggest that the underlying genetic architecture of pre‐eclampsia may be shared with other disorders, specifically hypertension and obesity.
Tweetable
A genetic predisposition to increased diastolic blood pressure and obesity increases the risk of pre‐eclampsia.
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A genetic predisposition to increased diastolic blood pressure and obesity increases the risk of pre‐eclampsia.
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