Dual mobility (DM) articulation total hip arthroplasty (THA) is used increasingly to reduce dislocation risk. We investigated cup fixation, polyethylene (PE) wear, serum chromium and cobalt ions, and ...their correlation to physical activity in patients with DM cups at 6-year follow-up.
In a patient-blinded RCT, 60 patients with hip osteoarthritis at a median age of 74 years (70-82) were randomly allocated to cemented (n = 30) or cementless hydroxyapatite-coated (n = 30) fixation of Avantage DM THA with a highly-crosslinked vitamin-E PE liner. Cup migration and PE wear were measured with radiostereometric analysis (RSA), chromium and cobalt ions were measured in serum, and physical activity was measured with accelerometers.
At 6-year follow-up, proximal cup migration was similar: 0.14 mm (95% CI 0.01-0.28) for cemented cups and 0.21 mm (0.02-0.39) for cementless cups. The PE wear rate from 1- to 6-year follow-up was also similar: 0.06 mm/year (0.04-0.09) for cemented cups and 0.07 mm/year (0.04-0.11) for cementless cups. Serum metal ion levels were undetectable or very low. Physical activity was mainly low intensity and did not correlate to PE wear rate or cup migration.
Cemented and cementless DM cups with highly crosslinked vitamin-E infused liners have similar cup migration and PE wear when used for primary THA surgery.
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DOBA, FSPLJ, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Background and purpose - Mortality after primary total hip and knee arthroplasty (THA and TKA) has declined, and the proportion of THA and TKA patients with comorbid conditions has increased. We ...therefore wanted to examine changes in comorbidity burden over time and the impact of comorbid on mortality following primary total hip and knee arthroplasty in patients with osteoarthritis.
Patients and methods - We used the Danish arthroplasty registers to identify THA and TKA patients from 1996 through 2013. From administrative databases, we collected data on pre-surgery hospital history for all patients, which were used to calculate the Charlson comorbidity index (CCI). Patients were divided into 4 groups: CCI-none, CCI-low, CCI-moderate, and CCI-high. We calculated the relative risk (RR) of mortality within 90 days after surgery with a 95% confidence interval (CI), with stratification according to CCI group and year of surgery.
Results - 99,962 THAs and 63,718 TKAs were included. The proportion of THAs with comorbidity increased by 3-4% in CCI-low, CCI-moderate, and CCI-high patients, from 1996-1999 to 2010-2013. The overall 90-day mortality risk declined for both procedures. Compared to CCI-none, THA patients with low, moderate, and high comorbidity burdens had an RR of 90-day mortality of 1.9 (95% CI: 1.6-2.4), 1.9 (CI: 1.5-2.5), and 3.3 (CI: 2.6-4.2), respectively. Similar increases in proportions and RRs were observed in TKAs.
Interpretation - Despite the fact that the proportion of THA and TKA patients with comorbidities has increased over the past 18 years, the overall mortality has declined. The mortality risk depended on the comorbidity burden and did not decline during the study period for THA and TKA patients with a moderate or high comorbidity burden at the time of surgery.
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DOBA, FSPLJ, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
BACKGROUND:Hydroxyethyl starch (HES) is commonly used as plasma expander during surgery but may be nephrotoxic as seen in studies in patients with sepsis. The authors hypothesized that the possible ...nephrotoxicity of 6% HES 130/0.4 could be revealed by measurements of urinary excretion of neutrophil gelatinase–associated lipocalin (u-NGAL) in patients with normal renal function during hip arthroplasty.
METHODS:In this randomized, double-blinded, placebo-controlled study, 40 patients referred for hip arthroplasty received either 6% HES 130/0.4 or isotonic saline 0.9%; 7.5 ml/kg during the first hour of surgery and 5 ml/kg during the following hours; 38 patients completed the study. U-NGAL, urine albumin, blood pressure, and plasma concentrations of creatinine, renin, NGAL, albumin, angiotensin-II, and aldosterone were measured before, during, and after surgery. U-NGAL was defined as primary outcome.
RESULTS:There were no significant differences in U-NGAL (mean difference and 95% CI), plasma creatinine, and urine albumin during the study. U-NGAL and urine albumin increased significantly in both groups the morning after surgery but was normalized at follow-up after 10 to 12 days. Mean arterial pressure was significantly higher during the recovery period in the HES group compared with that in the control group (91 13 and 83 6 mmHg, mean SD, P < 0.03). Plasma renin and angiotensin-II were nonsignificantly different in both groups, whereas plasma aldosterone was significantly lower in the HES group. Plasma albumin was reduced in both groups, but to a significantly lower level in the HES group.
CONCLUSION:The study showed no evidence of a harmful effect of intraoperative infusion of 6% HES 130/0.4 on renal function in patients during hip arthroplasty.
ObjectivesTo evaluate if higher cumulative occupational hand force requirements are associated with higher risks of surgery for trapeziometacarpal osteoarthritis and with surgery earlier in ...life.MethodsThe study was based on Danish national registers. Among all persons born in Denmark 1931 to 1990, we included those who had been employed for at least 5 years since 1991 by the end of 2000, or later when this employment criterion was reached, up until the end of 2016. Cumulative exposure estimates for 10-year time windows (force-years) were assessed by combining individual year-by-year information on occupational codes with an expert based hand-arm job exposure matrix. First-time events of surgery for trapeziometacarpal osteoarthritis 2001 to 2017 constituted the outcome. Surgery rates were analysed by a logistic regression technique equivalent to discrete survival analysis using a 1-year lag. We also calculated rate advancement periods.ResultsA total of 2 860 448 persons contributed with around 48 million person-years of follow-up, during which 3977 cases appeared (821 among men and 3156 among women). Compared with <5 force-years, the adjusted OR (ORadj) for ≥5 to <10 force-years was 1.39 (95% CI 1.14 to 1.68) and for ≥10 to 30 force-years 1.47 (95% CI 1.26 to 1.71) among men and 1.64 (95% CI 1.50 to 1.78) and 1.29 (95% CI 1.16 to 1.43) among women. The sex combined ORadj were 1.59 (95% CI 1.47 to 1.72) and 1.36 (95% CI 1.25 to 1.48). Among the exposed, surgery was advanced by 3 to 7 years.ConclusionMedium/high cumulative hand force requirements were associated with elevated hazard rates of surgery for trapeziometacarpal osteoarthritis and advanced the time of surgery by several years.
Tumor budding as a prognostic marker in colorectal cancer has not previously been investigated in a cohort of screened stage II colon cancer patients. We assessed the prognostic significance of tumor ...budding in a thoroughly characterized stage II colon cancer population comprising surgically resected patients in the Region of Southern Denmark from 2014 to 2016. Tumors were re-staged according to the 8th edition of UICC TNM Classification, undergoing detailed histopathological evaluation and tumor budding assessment following guidelines from the International Tumor Budding Consensus Conference. Prognostic evaluation utilized Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models for time to recurrence (TTR), recurrence-free survival (RFS), and overall survival (OS).
Out of 497 patients, 20% were diagnosed through the national colorectal cancer screening program. High-grade tumor budding (Bd3) was found in 19% of tumors and was associated with glandular subtype, perineural invasion, mismatch repair proficient tumors, and tumor recurrence (p < 0.001, p < 0.001, p = 0.045, and p = 0.007 respectively). In multivariable Cox regression, high-grade budding was a significant prognostic factor for TTR compared to low-grade (Bd3 HR 2.617; p = 0.007). An association between tumor budding groups and RFS was observed, and the difference was significant in univariable analysis for high-grade compared to low-grade tumor budding (Bd3 HR 1.461; p = 0.041). No significant differences were observed between tumor budding groups and OS.
High-grade tumor budding is a predictor of recurrence in a screened population of patients with stage II colon cancer and should be considered a high-risk factor in a shared decision-making process when stratifying patients to adjuvant chemotherapy.
•Tumor budding evaluation in a screened stage II colon cancer cohort.•Minimal adjustment set identified from causal directed acyclic graph.•Tumor budding a predictor of recurrence in patients with stage II colon cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Rectal cancer is a common disease with high mortality rates and limited therapeutic options. Here we combined the gene expression signatures of rectal cancer patients with the reverse drug-induced ...gene-expression profiles to identify drug repositioning candidates for cancer therapy. Among the predicted repurposable drugs, topoisomerase II inhibitors (doxorubicin, teniposide, idarubicin, mitoxantrone, and epirubicin) presented a high potential to reverse rectal cancer gene expression signatures. We showed that these drugs effectively reduced the growth of colorectal cancer cell lines closely representing rectal cancer signatures. We also found a clear correlation between topoisomerase 2A (TOP2A) gene copy number or expression levels with the sensitivity to topoisomerase II inhibitors. Furthermore, CRISPR-Cas9 and shRNA screenings confirmed that loss-of-function of the TOP2A has the highest efficacy in reducing cellular proliferation. Finally, we observed significant TOP2A copy number gains and increased expression in independent cohorts of rectal cancer patients. These findings can be translated into clinical practice to evaluate TOP2A status for targeted and personalized therapies based on topoisomerase II inhibitors in rectal cancer patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Risk stratification in Stage II and III colorectal cancer (CRC) patients is critical, as it allows patient selection for adjuvant chemotherapy. In view of the inadequacy of current ...clinicopathological features for risk‐stratification, we undertook a systematic and comprehensive biomarker discovery effort to develop a risk‐assessment signature in CRC patients. The biomarker discovery phase examined 853 CRC patients, and identified a gene signature for predicting recurrence‐free survival (RFS). This signature was validated in a meta‐analysis of 1212 patients from nine independent datasets, and its performance was compared against established prognostic signatures and consensus molecular subtypes (CMS). In addition, a risk‐prediction model was trained (n = 142), and subsequently validated in an independent clinical cohort (n = 286). As a result, this mesenchymal‐associated transcriptomic signature (MATS) identified high‐risk CRC patients with poor RFS in the discovery (hazard ratio HR: 1.79), and nine validation cohorts (HR: 1.86). In multivariate analysis, MATS was the most significant predictor of RFS compared to established prognostic signatures and CMS subtypes. Intriguingly, MATS robustly identified CMS4‐subtype in multiple CRC cohorts (AUC = 0.92‐0.99). In the two clinical cohorts, MATS stratified low and high‐risk groups with a 5‐year RFS in the training (HR: 4.11) and validation cohorts (HR: 2.55), as well as predicted response to adjuvant therapy in Stage II and III CRC patients. We report a novel prognostic and predictive biomarker signature in CRC, which is superior to currently used approaches and have the potential for clinical translation in near future.
What's new?
Numerous studies have tried to develop biomarkers or gene‐expression profiles to help predict which colorectal cancer (CRC) patients are most likely to benefit from adjuvant chemotherapies. In this study, the authors developed a “mesenchymal‐associated transcriptomic signature” (MATS) that was able to identify high‐risk CRC patients with poor recurrence‐free survival (RFS). In addition, the new MATS was able to predict the response of these patients to adjuvant therapy. Such biomarkers should lead to more appropriate risk stratification, and may improve survival outcomes in CRC patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We aimed to determine the prognosis after trapeziometacarpal total joint arthroplasty for basal thumb osteoarthritis with respect to sustainable return to work (RTW), pain, and disability. Our main ...hypothesis was that high occupational hand force requirements are related to slower RTW.
We conducted a 12-month follow-up study of patients who were treated with a trapeziometacarpal total joint arthroplasty in 2003 to 2015 and were active in the labor market at the time of surgery. We used registry information about RTW. Before surgery and at the 12-month follow-up, we obtained data on pain and disability. To obtain estimates of occupational hand force requirements for individual patients, we linked the patients’ self-reported job title to a job exposure matrix based on experts’ ratings. We used Cox regression models to analyze the time until sustainable RTW and logistic regression models to analyze pain and disability.
A total of 133 patients were included. Most patients returned to work within 12 months after surgery (86%). For those who returned to work within 12 months (n = 114), mean time until sustainable RTW was 14 weeks (SD, 9 weeks). Higher hand force requirements were associated with slower RTW (for medium- and high-force requirements, adjusted hazard ratios were 0.48 95% confidence interval, 0.30–0.78 and 0.41 95% confidence interval, 0.25-0.69). Occupational hand force requirements were not associated with pain and disability at follow-up.
High occupational hand force requirements were associated with slower RTW, but not with pain and disability 12 months after surgery.
Prognostic I.
Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis ...on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Limited data exists on the implementation process and safety of discharge on the day of surgery after primary hip and knee arthroplasty in a multicenter setting. We report our study protocol on the ...investigation of the feasibility, safety, and socioeconomic aspects following discharge on day of surgery after hip and knee arthroplasty across 8 fast-track centers.
This is a study protocol for a prospective cohort study on discharge on day of surgery from the Center for Fast-track Hip and Knee Replacement. The collaboration includes 8 centers covering 40% of the primary hip and knee arthroplasty procedures undertaken in Denmark. All patients scheduled for surgery are screened for eligibility using well-defined inclusion and exclusion criteria. Eligible patients fulfilling discharge criteria will be discharged on day of surgery. We expect to screen 9,000 patients annually. Duration and outcome: Patients will be enrolled over a 3-year period from September 2022 and reporting of results will run continuously until December 2025. We shall report the proportion of eligible patients and patients discharged on day of surgery as well as limiting factors. Readmissions and complications within 30 days are recorded with real-time follow-up by research staff. Furthermore, patient-reported information on willingness to repeat discharge on day of surgery, contacts with the healthcare system, complications, and workability is registered 30 days postoperatively. EQ-5D, Oxford Knee Score, and Oxford Hip Score are completed preoperatively and after 3 months and 1 year. Finally, outcome data will be used in the development of a prediction model for successful discharge on the day of surgery.
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DOBA, FSPLJ, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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