Circulating triglycerides are associated with human adipose tissue DNA methylation of genes linked to metabolic disease.

Dysregulation of circulating lipids is a central element for the metabolic syndrome. However, it is not well established whether human subcutaneous adipose tissue is affected by or affect circulating lipids through epigenetic mechanisms. Hence, our aim was to investigate the association between circulating lipids and DNA methylation levels in human adipose tissue. DNA methylation and gene expression were analysed genome-wide in subcutaneous adipose tissue from two different cohorts, including 85 men and 93 women, respectively. Associations between DNA methylation and circulating levels of triglycerides, low-density lipoprotein, high-density lipoprotein and total cholesterol were analysed. Causal mediation analyses tested if adipose tissue DNA methylation mediates the effects of triglycerides on gene expression or insulin resistance. We found 115 novel associations between triglycerides and adipose tissue DNA methylation, e.g. in the promoter of RFS1, ARID2 and HOXA5 in the male cohort (P ≤ 1.1 × 10-7), and 63 associations, e.g. within the gene body of PTPRN2 and COL6A3 in the female cohort. We further connected these findings to altered mRNA expression levels in adipose tissue (e.g. HOXA5, IL11 and FAM45B). Interestingly, there was no overlap between methylation sites associated with triglycerides in men and the sites found in women, which points towards sex-specific effects of triglycerides on the epigenome. Finally, a causal mediation analysis provided support for adipose tissue DNA methylation as a partial mediating factor between circulating triglycerides and insulin resistance. This study identified novel epigenetic alterations in adipose tissue associated with circulating lipids. Identified epigenetic changes seem to mediate effects of triglycerides on insulin resistance.

The Addition of the Gracilis Tendon to a Semitendinosus Tendon Autograft Is Not Associated With Knee Muscle Strength, Subjective Knee Function, or Revision Surgery After Anterior Cruciate Ligament Reconstruction.

PURPOSE: To evaluate and compare isokinetic knee muscle (extension and flexion) strength, single-leg hop (SLH) test performance, anterior knee laxity, subjective knee function, and the 2-year revision surgery risk between patients who underwent anterior cruciate ligament reconstruction (ACLR) with semitendinosus tendon (ST) autografts and patients who underwent ACLR with ST and gracilis tendon (ST-G) autografts. METHODS: We identified patients aged 16 years or older who underwent primary ACLR with hamstring tendon autografts at our institution from January 2005 to December 2020 and had no associated ligament injuries. Isokinetic knee muscle strength and SLH test performance were assessed 6 months postoperatively. Anterior knee laxity (KT-1000 arthrometer, 134 N) was assessed preoperatively and 6 months postoperatively. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was collected preoperatively and 1 and 2 years postoperatively. Patients who underwent revision ACLR at any institution in Sweden within 2 years of primary surgery were identified through the Swedish National Knee Ligament Registry. RESULTS: A total of 6,974 patients (5,479 with ST and 1,495 with ST-G) were included. There were no significant differences in extension and flexion strength or SLH test performance between the groups. Preoperatively, there was no significant difference in knee laxity between the ST and ST-G groups. Postoperatively, the ST-G group had significantly increased mean side-to-side (STS) laxity (2.1 ± 2.3 mm vs 1.7 ± 2.2 mm, P < .001) and showed a trend toward increased STS laxity according to the International Knee Documentation Committee form, with significantly fewer patients with STS laxity of 2 mm or less (58.4% vs 65.8%) and significantly more patients with STS laxity between 3 and 5 mm (35.0% vs 29.9%) or greater than 5 mm (6.6% vs 4.3%) (P < .001). The only significant difference in subjective knee function was for the KOOS Quality of Life subscale score in favor of the ST group preoperatively (37.3 ± 21.4 vs 35.1 ± 19.9, P = .001). No other significant differences between the groups were found preoperatively and 1 and 2 years postoperatively for any of the KOOS subscales. The overall revision ACLR rate within 2 years of primary surgery was 2.0% (138 of 6,974 patients). The revision ACLR risk in the ST-G group (1.7%, 25 of 1,495 patients) was not significantly different from that in the ST group (2.1%, 113 of 5,479 patients) (hazard ratio, 0.80; 95% confidence interval, 0.50-1.24; P = .32). CONCLUSIONS: The addition of the gracilis tendon to an ST autograft was not associated with knee muscle strength, SLH test performance, subjective knee function, or the risk of revision surgery after ACLR. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Tips and tricks for how to become a good reviewer.

Peer review is an essential process to ensure that scientific articles meet high standards of methodology, ethics and quality. The peer-review process is a part of the academic mission for physicians in the university setting. The work of reviewers is of great value for authors, as it gives constructive criticism and improves manuscript quality before publication. Often, however, reviews are of suboptimal quality. Usually, reviewers do not receive formal training either on how to perform a review or on the peer-review process. In addition, it is generally believed that experienced authors are great reviewers, but this may not always be true. The overarching goal of a review is to make the manuscript better; to help the authors. The purpose of this article is to offer relevant suggestions and provide a checklist on how to perform a useful review.

Management of anterior cruciate ligament revision in adults: the 2022 ESSKA consensus part I-diagnostics and preoperative planning.

PURPOSE: The aim of this ESSKA consensus is to give recommendations based on evidence and expert opinion to improve diagnosis, preoperative planning, indication and surgical strategy in ACL revision. METHODS: The European expert surgeons and scientists were divided into four groups to participate in this consensus. A "literature group" (four surgeons); "steering group" (14 surgeons and scientists); "rating group" (19 surgeons) and finally "peer review group" (51 representatives of the ESSKA-affiliated national societies from 27 countries). The steering group prepared eighteen question-answer sets. The quality of the answers received grades of recommendation ranging from A (high-level scientific support), to B (scientific presumption), C (low level scientific support) or D (expert opinion). These question-answer sets were then evaluated by the rating group. All answers were scored from 1 to 9. The comments of the rating group were incorporated by the steering group and the consensus was submitted to the rating group a second time. Once a general consensus was reached between the steering and rating groups, the question-answer sets were submitted to the peer review group. A final combined meeting of all the members of the consensus was held to ratify the document. RESULTS: The literature review for the diagnosis and preoperative planning of ACL revision revealed a rather low scientific quality. None of the 18 questions was graded A and six received a grade B. The mean rating of all the questions by the rating group was 8.4 ± 0.3. The questions and recommendations are listed below. CONCLUSION: ACL revision surgery is a widely debated subject with many different opinions and techniques. The literature reveals a poor level of standardisation. Therefore, this international consensus project is of great importance. LEVEL OF EVIDENCE: II.

Management of anterior cruciate ligament revision in adults: the 2022 ESSKA consensus: part II-surgical strategy.

PURPOSE: The aim of this ESSKA consensus is to give recommendations based on scientific evidence and expert opinion to improve the diagnosis, preoperative planning, indication and surgical strategy in Anterior Cruciate Ligament revision. METHODS: Part 2, presented herein, followed exactly the same methodology as Part 1: the so-called ESSKA formal consensus derived from the Delphi method. Eighteen questions were ultimately asked. The quality of the answers received the following grades of recommendation: Grade A (high level scientific support), Grade B (scientific presumption), Grade C (low level scientific support) or Grade D (expert opinion). All answers were scored from 1 to 9 by the raters. Once a general consensus had been reached between the steering and rating groups, the question-answer sets were submitted to the peer-review group. A final combined meeting of all the members of the consensus was then held to ratify the document. RESULTS: The review of the literature revealed a rather low scientific quality of studies examining the surgical strategy in cases of ACL reconstruction failure. Of the 18 questions, only 1 received a Grade A rating; 5, a Grade B rating; and 9, grades of C or D. The three remaining complex questions received further evaluations for each portion of the question and were looked at in more detail for the following grades: B and D; A, C and D; or A, B, C and D. The mean rating of all questions by the rating group was 8.0 + - 1.1. The questions and recommendations are listed in the article. CONCLUSION: ACL revision surgery, especially the surgical strategy, is a widely debated subject with many different opinions and techniques. The literature reveals a poor level of standardization. Therefore, this international European consensus project is of great importance and clinical relevance for guiding the management of ACL revision in adults. LEVEL OF EVIDENCE: Level II.

High degree of consensus amongst an expert panel regarding focal resurfacing of chondral and osteochondral lesions of the femur with mini-implants.

INTRODUCTION: The rationale for the use of mini-implants for partial resurfacing in the treatment of femoral chondral and osteochondral lesions is still under debate. The evidence supporting best practise guidelines is based on studies with low-level evidence. A consensus group of experts was convened to collaboratively advance towards consensus opinions regarding the best available evidence. The purpose of this article is to report the resulting consensus statements. METHODS: Twenty-five experts participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted via an online survey of two rounds, for initial agreement and comments on the proposed statements. An in-person meeting between the panellists was organised during the 2022 ESSKA congress to further discuss and debate each of the statements. A final agreement was made via a final online survey a few days later. The strength of consensus was characterised as: consensus, 51-74% agreement; strong consensus, 75-99% agreement; unanimous, 100% agreement. RESULTS: Statements were developed in the fields of patient assessment and indications, surgical considerations and postoperative care. Between the 25 statements that were discussed by this working group, 18 achieved unanimous, whilst 7 strong consensus. CONCLUSION: The consensus statements, derived from experts in the field, represent guidelines to assist clinicians in decision-making for the appropriate use of mini-implants for partial resurfacing in the treatment of femoral chondral and osteochondral lesions. LEVEL OF EVIDENCE: Level V.

Autologous semitendinosus tendon graft could function as a meniscal transplant.

PURPOSE: Meniscectomy results in poor knee function and increased risk for osteoarthritis. Meniscal allograft transplantation is not widely used due to costs and availability. The semitendinosus tendon (ST) has the potential to remodel and revascularize in an intraarticular environment, such as ACL reconstruction. The objective for this pilot study was to investigate whether the ST graft could function as a meniscal transplant. METHODS: The ST was doubled and sutured with running sutures and pull-out sutures in each end. Bone tunnels were used for root anchorage and the graft was sutured with allinside, inside-out and outside-in technique. The pull-out sutures were fixed over a button. Partial weight bearing was allowed with limited range of motion in a brace for the first 6 weeks. Evaluation was assessed using clinical examination, radiology and patient reported outcome. RESULTS: A total of seven patients have been included between January 2018 and June 2020. Six medial transplants and one lateral transplant were performed. Mean age was 29 years. Four patients had completed the 12-month follow-up. Improvements were noted for IKDC Global Score, KOOS pain subscale and Lysholm. MRI indicated that the transplant become more wedge-like with visible roots and minor protrusion. CONCLUSIONS: Even though this is primarily a technical report the follow-up data indicate that the transplant survives and adapts in shape and capabilities to an original meniscus. There were no adverse events and the patients seem to improve in terms of pain and quality of life.

Failed meniscal repair increases the risk for osteoarthritis and poor knee function at an average of 9 years follow-up.

PURPOSE: The purpose of this study was to determine the effect of meniscal repair on OA in the knee joint and patient-related outcomes. METHODS: Three-hundred and sixteen meniscal repairs performed between 1999 and 2011 were analysed. Patient-related outcome measures were assessed through mailed questionnaires including KOOS, Lysholm score and Tegner activity level. Patients answering the questionnaires were encouraged to perform a radiographic evaluation with Rosenberg views, assessed according to Kellgren-Lawrence (KL) classification. The primary endpoint was to determine the effect of meniscal repair on the development of radiographic OA defined as a KL grade 2 or more. RESULTS: Mean follow-up time was 9.3 years (SD 3.6), 162 (51%) patients answered the questionnaires, and 86 patients completed the X-ray. The odds ratio for OA with a failed meniscus repair was 5.1 (p = 0.007) adjusted for gender and age at time of follow-up. KOOS showed a clinically important difference in the sport and recreation subscale (p = 0.041). CONCLUSIONS: There was an increased risk for OA in the affected compartment with a failed meniscus fixation. This supports the fact that the meniscus is an important protector of the cartilage in the knee. The meniscus injury affects the long-term health-related quality of life according to KOOS and in light of this study we recommend repair of a torn meniscus whenever possible. LEVEL OF EVIDENCE: III.

Age, time from injury to surgery and hop performance after primary ACLR affect the risk of contralateral ACLR.

PURPOSE: To evaluate factors affecting the risk of contralateral anterior cruciate ligament reconstruction (ACLR) within 5 years of primary ACLR. METHODS: Primary ACLRs performed at Capio Artro Clinic, Stockholm, Sweden, during the period 2005-2014, were reviewed. The outcome of the study was the occurrence of contralateral ACLR within 5 years of primary ACLR. Univariable and multivariable logistic regression analyses were employed to identify preoperative [age, gender, body mass index (BMI), time from injury to surgery, pre-injury Tegner activity level], intraoperative [graft type, medial meniscus (MM) and lateral meniscus (LM) resection or repair, cartilage injury] and postoperative [limb symmetry index (LSI) for quadriceps and hamstring strength and single-leg-hop test performance at 6 months] risk factors for contralateral ACLR. RESULTS: A total of 5393 patients who underwent primary ACLR were included. The incidence of contralateral ACLR within 5 years was 4.7%. Univariable analysis revealed that age ≥ 25 years, BMI ≥ 25 kg/m2, time from injury to surgery ≥ 12 months and the presence of a cartilage injury reduced the odds, whereas female gender, pre-injury Tegner activity level ≥ 6, quadriceps and hamstring strength and a single-leg-hop test LSI of ≥ 90% increased the odds of contralateral ACLR. Multivariable analysis showed that the risk of contralateral ACLR was significantly affected only from age ≥ 25 years (OR 0.40; 95% CI 0.28-0.58; P < 0.001), time from injury to surgery ≥ 12 months (OR 0.48; 95% CI 0.30-0.75; P = 0.001) and a single-leg-hop test LSI of ≥ 90% (OR 1.56; 95% CI 1.04-2.34; P = 0.03). CONCLUSION: Older age (≥ 25 years) and delayed primary ACLR (≥ 12 months) reduced the odds, whereas a symmetrical (LSI ≥ 90%) 6-month single-leg-hop test increased the odds of contralateral ACLR within 5 years of primary ACLR. Knowledge of the factors affecting the risk of contralateral ACLR is important when it comes to the appropriate counselling for primary ACLR. Patients should be advised regarding factors affecting the risk of contralateral ACLR. LEVEL OF EVIDENCE: Level III.

Minimal graft site morbidity using autogenous semitendinosus graft from the uninjured leg: a randomised controlled trial.

PURPOSE: To quantify the effect on strength of semitendinosus (ST) graft harvest by comparing isokinetic and isometric muscle strength. METHODS: A cohort of 140 patients underwent anterior cruciate ligament (ACL) reconstruction (ACLR) and were randomized to ipsilateral or contralateral ST graft harvest. Isokinetic and isometric muscle strength testing using a dynamometer were collected for the operated and non-operated leg. Patients were assessed pre-surgery and at 6, 12 and 24 months after reconstruction. RESULTS: ST graft harvest reduced isokinetic flexion muscle strength for 6 months. At 12 months follow up there was no significant difference between the two groups and they were all stronger than pre-injury. No other significant differences were found in any primary or secondary outcome measurements. CONCLUSION: Solitary ST graft harvest does not appear to result in a permanent reduced isometric or isokinetic quadriceps muscle strength on the side where the graft is harvested. A reduction in hamstring muscle strength of less than 10% can be seen at short-term follow-up with full recovery by 12 months. Most patients report little or no donor site pain. Given these findings, ST autograft is an alternative graft choice that could be used for various reconstructions in terms of donor site morbidity. LEVEL OF EVIDENCE: Level II.

Compensation claims following anterior cruciate ligament injuries reported to the patient insurance company in Sweden in 2005-2014.

Background and purpose - Patients in the Swedish healthcare system are insured against avoidable adverse events via Landstingens Ömsesidiga Försäkringsbolag (LÖF). We assessed the reasons for compensation claims reported to LÖF following an ACL injury. Patients and methods - We searched the LÖF database for compensation claims related to ACL injuries reported in 2005-2014, and cross-matched claims with the Swedish National Knee Ligament Register. We then performed a review of the medical records. Results - We identified 530 eligible claims in 2005-2014. 352 (66%) claims were accepted by LÖF and 178 claims were rejected. Accepted claims corresponded to fewer than 1% of ACL surgeries performed in the same period. The most common reasons for an accepted claim were postoperative septic arthritis followed by suboptimal surgery and delay in diagnosis and treatment. Interpretation - There are different reasons for accepting a compensation claim following an ACL injury, which represents different treatment errors that can be avoided.

Quantitative proteomic analysis of human peripheral nerves from subjects with type 2 diabetes.

AIMS: Diabetic peripheral neuropathy (DPN) is a common and severe complication to type 2 diabetes. The pathogenesis of DPN is not fully known, but several pathways and gene polymorphisms contributing to DPN are described. DPN can be studied using nerve biopsies, but studies on the proteome of the nerve itself, and its surrounding tissue as a whole, are lacking. Studies on the posterior interosseous nerve (PIN) have proposed PIN a useful indicator of DPN. METHODS: A quantitative mass spectrometry-based proteomics analysis was made of peripheral nerves from age- and gender-matched living human male tissue donors; nine type 2 diabetes subjects, with decreased sural nerve action potentials indicating DPN, and six controls without type 2 diabetes, with normal electrophysiology results. RESULTS: A total of 2617 proteins were identified. Linear regression was used to discover which proteins were differentially expressed between type 2 diabetes and controls. Only soft signals were found. Therefore, clustering of the 500 most variable proteins was made to find clusters of similar proteins in type 2 diabetes subjects and healthy controls. CONCLUSIONS: This feasibility study shows, for the first time, that the use of quantitative mass spectrometry enables quantification of proteins from nerve biopsies from subjects with and without type 2 diabetes, which may aid in finding biomarkers of importance to DPN development.

Relationship between insulin sensitivity and gene expression in human skeletal muscle.

BACKGROUND: Insulin resistance (IR) in skeletal muscle is a key feature of the pre-diabetic state, hypertension, dyslipidemia, cardiovascular diseases and also predicts type 2 diabetes. However, the underlying molecular mechanisms are still poorly understood. METHODS: To explore these mechanisms, we related global skeletal muscle gene expression profiling of 38 non-diabetic men to a surrogate measure of insulin sensitivity, i.e. homeostatic model assessment of insulin resistance (HOMA-IR). RESULTS: We identified 70 genes positively and 110 genes inversely correlated with insulin sensitivity in human skeletal muscle, identifying autophagy-related genes as positively correlated with insulin sensitivity. Replication in an independent study of 9 non-diabetic men resulted in 10 overlapping genes that strongly correlated with insulin sensitivity, including SIRT2, involved in lipid metabolism, and FBXW5 that regulates mammalian target-of-rapamycin (mTOR) and autophagy. The expressions of SIRT2 and FBXW5 were also positively correlated with the expression of key genes promoting the phenotype of an insulin sensitive myocyte e.g. PPARGC1A. CONCLUSIONS: The muscle expression of 180 genes were correlated with insulin sensitivity. These data suggest that activation of genes involved in lipid metabolism, e.g. SIRT2, and genes regulating autophagy and mTOR signaling, e.g. FBXW5, are associated with increased insulin sensitivity in human skeletal muscle, reflecting a highly flexible nutrient sensing.

Utilizing a contralateral hamstring autograft facilitates earlier isokinetic and isometric strength recovery after anterior cruciate ligament reconstruction: a randomised controlled trial.

PURPOSE: To compare muscle strength and patient reported outcomes following ACLR using a semitendinosus (ST) graft from the ipsilateral (IL) leg compared to a graft from the contralateral (CL) leg. METHODS: One-hundred and forty patients with an ACL injury were randomized to IL or CL ACLR. Patients were assessed at 6, 12 and 24 months with isokinetic and isometric muscle strength measured using Biodex. Patient-reported outcomes and manual stability measurements were also recorded. RESULTS: Patient-related outcomes improved over time for both groups with no significant differences between groups at any time point. No differences between groups in objective knee assessment scores or rerupture rates were found. The IL group was significantly weaker in knee flexion strength at all time points compared to the CL group, additionally the IL group did not recover flexor strength within 2 years. CONCLUSION: This study demonstrated that utilizing an ST graft harvested from the uninjured limb for ACLR facilitates early isokinetic and isometric strength recovery, with no significant adverse outcomes demonstrated in other measurements and therefore be performed to reduce the risk of long-term strength deficits in the injured leg LEVEL OF EVIDENCE: II.

Age, time from injury to surgery and quadriceps strength affect the risk of revision surgery after primary ACL reconstruction.

PURPOSE: To identify preoperative, intraoperative and postoperative factors associated with revision anterior cruciate ligament reconstruction (ACLR) within 2 years of primary ACLR. METHODS: Patients who underwent primary ACLR at our institution, from January 2005 to March 2017, were identified. The primary outcome was the occurrence of revision ACLR within 2 years of primary ACLR. Univariate and multivariate logistic regression analyses were used to evaluate preoperative [age, gender, body mass index (BMI), time from injury to surgery, pre-injury Tegner activity level], intraoperative [graft type, graft diameter, medial meniscus (MM) and lateral meniscus (LM) resection or repair, cartilage injury] and postoperative [side-to-side (STS) anterior laxity, limb symmetry index (LSI) for quadriceps and hamstring strength and single-leg-hop test performance at 6 months] risk factors for revision ACLR. RESULTS: A total of 6,510 primary ACLRs were included. The overall incidence of revision ACLR within 2 years was 2.5%. Univariate analysis showed that age < 25 years, BMI < 25 kg/m2, time from injury to surgery < 12 months, pre-injury Tegner activity level ≥ 6, LM repair, STS laxity > 5 mm, quadriceps strength and single-leg-hop test LSI of ≥ 90% increased the odds; whereas, MM resection and the presence of a cartilage injury reduced the odds of revision ACLR. Multivariate analysis revealed that revision ACLR was significantly related only to age < 25 years (OR 6.25; 95% CI 3.57-11.11; P < 0.001), time from injury to surgery < 12 months (OR 2.27; 95% CI 1.25-4.17; P = 0.007) and quadriceps strength LSI of ≥ 90% (OR 1.70; 95% CI 1.16-2.49; P = 0.006). CONCLUSION: Age < 25 years, time from injury to surgery < 12 months and 6-month quadriceps strength LSI of ≥ 90% increased the odds of revision ACLR within 2 years of primary ACLR. Understanding the risk factors for revision ACLR has important implications when it comes to the appropriate counseling for primary ACLR. In this study, a large spectrum of potential risk factors for revision ACLR was analyzed in a large cohort. Advising patients regarding the results of an ACLR should also include potential risk factors for revision surgery. LEVEL OF EVIDENCE: III.

Patient-specific metal implants for focal chondral and osteochondral lesions in the knee; excellent clinical results at 2 years.

PURPOSE: Surgical treatment options for the management of focal chondral and osteochondral lesions in the knee include biological solutions and focal metal implants. A treatment gap exists for patients with lesions not suitable for arthroplasty or biologic repair or who have failed prior cartilage repair surgery. This study reports on the early clinical and functional outcomes in patients undergoing treatment with an individualised mini-metal implant for an isolated focal chondral defect in the knee. METHODS: Open-label, multicentre, non-randomised, non-comparative retrospective observational analysis of prospectively collected clinical data in a consecutive series of 80 patients undergoing knee reconstruction with the Episealer® implant. Knee injury and Osteoarthritis Outcome Score (KOOS) and VAS scores, were recorded preoperatively and at 3 months, 1 year, and 2 years postoperatively. RESULTS: Seventy-five patients were evaluated at a minimum 24 months following implantation. Two patients had undergone revision (2.5%), 1 declined participation, and 2 had not completed the full data requirements, leaving 75 of the 80 with complete data for analysis. All 5 KOOS domain mean scores were significantly improved at 1 and 2 years (p < 0.001-0.002). Mean preoperative aggregated KOOS4 of 35 (95% CI 33.5-37.5) improved to 57 (95% CI 54.5-60.2) and 59 (95% CI 55.7-61.6) at 12 and 24 months respectively (p < 0.05). Mean VAS score improved from 63 (95% CI 56.0-68.1) preoperatively to 32 (95% CI 24.4-38.3) at 24 months. The improvement exceeded the minimal clinically important difference (MCID) and this improvement was maintained over time. Location of defect and history of previous cartilage repair did not significantly affect the outcome (p > 0.05). CONCLUSION: The study suggests that at 2 years, Episealer® implants are safe with a low failure rate of 2.5% and result in clinically significant improvement. Individualised mini-metal implants with appropriate accurate guides for implantation appear to have a place in the management of focal femoral chondral and osteochondral defects in the knee. LEVEL OF EVIDENCE: IV.

Evaluation of small nerve fiber dysfunction in type 2 diabetes.

OBJECTIVES: To assess potential correlations between intraepidermal nerve fiber densities (IENFD), graded with light microscopy, and clinical measures of peripheral neuropathy in elderly male subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM), respectively. MATERIALS AND METHODS: IENFD was assessed in thin sections of skin biopsies from distal leg in 86 men (71-77 years); 24 NGT, 15 IGT, and 47 T2DM. Biopsies were immunohistochemically stained for protein gene product (PGP) 9.5, and intraepidermal nerve fibers (IENF) were quantified manually by light microscopy. IENFD was compared between groups with different glucose tolerance and related to neurophysiological tests, including nerve conduction study (NCS; sural and peroneal nerve), quantitative sensory testing (QST), and clinical examination (Total Neuropathy Score; Neuropathy Symptom Score and Neuropathy Disability Score). RESULTS: Absent IENF was seen in subjects with T2DM (n = 10; 21%) and IGT (n = 1; 7%) but not in NGT. IENFD correlated weakly negatively with HbA1c (r = -.268, P = .013) and Total Neuropathy Score (r = -.219, P = .042). Positive correlations were found between IENFD and sural nerve amplitude (r = .371, P = .001) as well as conduction velocity of both the sural (r = .241, P = .029) and peroneal nerve (r = .258, P = .018). Proportions of abnormal sural nerve amplitude became significantly higher with decreasing IENFD. No correlation was found with QST. Inter-rater reliability of IENFD assessment was good (ICC = 0.887). CONCLUSIONS: Signs of neuropathy are becoming more prevalent with decreasing IENFD. IENFD can be meaningfully evaluated in thin histopathological sections using the presented technique to detect neuropathy.

Triclosan changes community composition and selects for specific bacterial taxa in marine periphyton biofilms in low nanomolar concentrations.

The antibacterial agent Triclosan (TCS) is a ubiquitous environmental contaminant due to its widespread use. Sensitivity to TCS varies substantially among eu- and pro-karyotic species and its risk for the marine environment remains to be better elucidated. In particular, the effects that TCS causes on marine microbial communities are largely unknown. In this study we therefore used 16S amplicon rDNA sequencing to investigate TCS effects on the bacterial composition in marine periphyton communities that developed under long-term exposure to different TCS concentrations. Exposure to TCS resulted in clear changes in bacterial composition already at concentrations of 1 to 3.16 nM. We conclude that TCS affects the structure of the bacterial part of periphyton communities at concentrations that actually occur in the marine environment. Sensitive taxa, whose abundance decreased significantly with increasing TCS concentrations, include the Rhodobiaceae and Rhodobacteraceae families of Alphaproteobacteria, and unidentified members of the Candidate division Parcubacteria. Tolerant taxa, whose abundance increased significantly with higher TCS concentrations, include the families Erythrobacteraceae (Alphaproteobacteria), Flavobacteriaceae (Bacteroidetes), Bdellovibrionaceae (Deltaproteobacteria), several families of Gammaproteobacteria, and members of the Candidate phylum Gracilibacteria. Our results demonstrate the variability of TCS sensitivity among bacteria, and that TCS can change marine bacterial composition at concentrations that have been detected in the marine environment.

Acute ACL reconstruction shows superior clinical results and can be performed safely without an increased risk of developing arthrofibrosis.

PURPOSE: To compare acute ACL reconstruction (ACLR) within 8 days of injury with delayed reconstruction after normalized range of motion (ROM), 6-10 weeks after injury. It was hypothesized that acute ACL reconstruction with modern techniques is safe and can be beneficial in terms of patient-reported outcomes and range of motion. METHODS: The effect of acute and delayed ACLR was randomized studied on 70 patients with high recreational activity level, Tegner level 6 or more, between 2006 and 2013. Patient-reported outcomes, objective IKDC, KOOS, and manual stability measurements were documented during the 24-month follow-up period. RESULTS: The acute ACLR group did not result in increased stiffness and showed superior outcome regarding strength and how the patient felt their knee functioning at 24 months. In addition, the acute group was not inferior to the delayed group in any assessment. Regarding patient-related outcomes in KOOS, both groups showed significant improvements in all subscales, but no difference was found between the groups. Functional return (FR) rate was almost double compared to the Swedish knee ligament register and treatment failure (TF) rate was reduced by half, no significant difference between the groups. No difference regarding cyclops removal, re-injury of ACL or meniscus was found between the two surgical timing groups. CONCLUSION: Acute ACLR within 8 days of injury does not appear to adversely affect ROM or result in increased stiffness in the knee joint and was not inferior to the delayed group in any assessment when compared to delayed surgery. LEVEL OF EVIDENCE: I.

Acute reconstruction results in less sick-leave days and as such fewer indirect costs to the individual and society compared to delayed reconstruction for ACL injuries.

PURPOSE: To compare the total number of sick-leave days caused by the knee injury from the day of injury and over the first year between acute (within 8 days) and delayed (6-10 weeks) anterior cruciate ligament reconstruction (ACLR) and also assess other clinical outcomes during this period. METHODS: Seventy patients with an acute ACL injury and Tegner level of 6 or more were randomized to acute (within 8 days) or delayed (after 6-10 weeks) ACLR. Patient-reported outcomes; objective IKDC and manual stability measurements were assessed at 6 and 12 months. With data from the Swedish Social Insurance Agency (Försäkringskassan) information about the number of sick-leave days due to the knee injury over the following 12 months was collected and compared between the two groups. RESULTS: Seventy-one percent received compensation for sick leave (26 in the acute versus 23 in the delayed group). The mean number of sick-leave days for the acute group was significantly lower (M = 56.9, SD = 36.4) compared to the delayed group (M = 88.5, SD = 50.2), p < 0.05. The acute group was also significantly stronger in flexion in both slow and fast angle velocities according to Biodex®. No other differences were found between the groups in other clinical assessments or in terms of associated injuries. CONCLUSION: Acute and delayed ACLR provided comparable clinical outcomes after 12 months. Acute reconstruction resulted in less sick-leave days and as such fewer indirect costs to the individual and society. These findings suggest that if patients requiring ACLR can be identified early and ACLR can be performed in the acute phase, socioeconomic costs can potentially be reduced by minimizing time off work. LEVEL OF EVIDENCE: II.