Nonoperative Treatment as an Option for Isolated Anterior Cruciate Ligament Injury: A Systematic Review and Meta-analysis.

Background: An anterior cruciate ligament (ACL) tear is a risk factor for early osteoarthritis (OA) onset. Generally, ACL reconstruction (ACLR) is associated with better outcomes. However, there is a lack of evidence regarding the effect of operative versus nonoperative treatment for preventing premature knee OA in isolated ACL tears while achieving good functional outcomes. Purpose/Hypothesis: The purpose of the study was to compare the outcomes of ACLR to primarily nonoperative management of isolated ACL tears. It was hypothesized that the outcomes between treatment types would be similar. Study Design: Systematic review; Level of evidence, 3. Methods: This systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (registration No. CRD42021285901) and was conducted according to the Cochrane Handbook guidelines. We systematically searched for randomized and nonrandomized studies that compared ACLR with nonoperative treatments in isolated ACL tears in 3 databases until October 25, 2021. The risk of bias and quality of evidence of the included studies was assessed in accordance with the Cochrane guidelines. The primary outcome was radiologic signs of OA, and the secondary outcomes were functional parameters. Using the common effects model, we calculated pooled mean differences (MDs) and odds ratios (ORs) with 95% CIs. Results: Five studies-2 randomized controlled trials (RCTs) and 3 retrospective non-RCTs-were included. There was a moderate risk of bias in 2 studies and a serious risk of bias in 1 study. The quality of evidence was rated low because of the higher risk of bias and inconsistency. Nonoperatively treated knees showed a trend toward lower odds of developing radiological signs of OA (OR, 1.84 [95% CI, 0.90 to 3.75]); however, surgically reconstructed knees had significantly better stability (MD, -2.44 [95% CI, -3.21 to -1.66 ]) and a trend toward better but clinically not meaningful Lysholm scores (MD, 2.88 [95% CI, -1.09 to 6.85]). The qualitative synthesis showed that surgical reconstruction was protective against subsequent injuries but not superior when returning to previous activity levels or various functional tests. Conclusion: Findings indicated that there is no certain evidence that ACLR for an isolated ACL tear is superior to nonoperative treatment. Clinicians should consider nonoperative treatments with a well-designed rehabilitative program as a primary option. However, these findings must be interpreted with caution because of low study quality and high risk of bias.

The effect of sterilization and storage on the viscoelastic properties of human tendon allografts - Continued: Storage for 0 to 4 months.

The role of donor-derived tendons, also known as allografts, in anterior cruciate ligament replacement surgeries is steadily increasing. Before surgery, temporary storage and, in most cases, sterilization are essential. It is, thus, crucial to determine how these procedures alter the grafts' biomechanical properties. The purpose of this research was to analyze the effect of different sterilization methods (native, frozen, frozen + 21 kGy gamma irradiation, frozen + 21 kGy electron beam irradiation) and storage durations (0 to 4 months) on the deformation and creep of two tendon types (tibialis anterior, peroneus longus). 80 tibialis anterior and 83 peroneus longus tendons from 51 human cadavers were included. The samples were removed, placed in a radio-cryoprotectant solution, then slowly cooled, sterilized and stored at -80 °C. All groups were subject to 60 s static creep test with 250 N load. Deformation during the loading phase, creep during static loading, and the ratio of these two were evaluated. Deformation at the end of the loading phase and creep consistently exhibited significantly smaller values in the tibialis anterior compared to the peroneus longus type, as well as in electron beam-sterilized grafts as opposed to gamma beam-sterilized ones. Prolonged storage periods (within 0 to 4 months) resulted in a notable increase in these values, particularly in deformation. Based on the experimental data, the tibialis anterior tendon type and sterilization by gamma beam irradiation are better choices for anterior cruciate ligament reconstruction than the peroneus longus and sterilization by electron beam. Increased storage time affects negatively the evaluated mechanical properties.

Unique, Specific CART Receptor-Independent Regulatory Mechanism of CART(55-102) Peptide in Spinal Nociceptive Transmission and Its Relation to Dipeptidyl-Peptidase 4 (DDP4).

Cocaine- and amphetamine-regulated transcript (CART) peptides are involved in several physiological and pathological processes, but their mechanism of action is unrevealed due to the lack of identified receptor(s). We provided evidence for the antihyperalgesic effect of CART(55-102) by inhibiting dipeptidyl-peptidase 4 (DPP4) in astrocytes and consequently reducing neuroinflammation in the rat spinal dorsal horn in a carrageenan-evoked inflammation model. Both naturally occurring CART(55-102) and CART(62-102) peptides are present in the spinal cord. CART(55-102) is not involved in acute nociception but regulates spinal pain transmission during peripheral inflammation. While the full-length peptide with a globular motif contributes to hyperalgesia, its N-terminal inhibits this process. Although the anti-hyperalgesic effects of CART(55-102), CART(55-76), and CART(62-76) are blocked by opioid receptor antagonists in our inflammatory models, but not in neuropathic Seltzer model, none of them bind to any opioid or G-protein coupled receptors. DPP4 interacts with Toll-like receptor 4 (TLR4) signalling in spinal astrocytes and enhances the TLR4-induced expression of interleukin-6 and tumour necrosis factor alpha contributing to inflammatory pain. Depending on the state of inflammation, CART(55-102) is processed in the spinal cord, resulting in the generation of biologically active isoleucine-proline-isoleucine (IPI) tripeptide, which inhibits DPP4, leading to significantly decreased glia-derived cytokine production and hyperalgesia.

Nonlinear fiber-bundle-cells-based phenomenological modeling of human tissue samples.

Certain assemblies of fibers, called fiber bundles, play a crucial role in the statistical macroscale properties of fibrous structures like natural or artificial materials. Based on the concept of using idealized statistical fiber bundle cells (FBCs) as model elements, the software named FiberSpace was developed by us earlier for the phenomenological modeling of the tensile test process of real fibrous structures. The model fibers of these FBCs had been considered linear elastic, which was suitable for modeling certain textiles and composites. However, the biological tissues are multilevel structures with fiber-like building elements on every structural level where the fiber elements on the dominant level are statistical bundles of elementary fibers. Hence, their modeling required us to introduce model fibers of nonlinear mechanical behavior and derive the proper mathematical formulas for the calculation of the expected tensile force processes of the FBCs. Accordingly, we developed a new version of FiberSpace. The proposed nonlinear FBCs-based modeling method is essentially phenomenological that decomposes the measured and averaged stress-strain curve into the weighted sum of the responses of different idealized nonlinear FBCs. However, this decomposition can give certain information about the fibrous structure and some details of its damage and failure sub-processes. A special application of nonlinear E-bundles, where the measured stress-strain curve is expanded into a product-function series, may give another type of description for the failure process and can be applied to single measurements of structured failure process containing significant peaks and drops as well. The fitted phenomenological FBC models provide a decomposition of the measured force-strain curve, which enables to construct informative damage and failure maps. The applicability of the phenomenological modeling method and the fitting procedure is demonstrated with the tensile test data of some human and animal tissues, such as facial nerves and tendons.

The effect of sterilization and storage on the viscoelastic properties of human tendon allografts.

Allografts have become increasingly preferred for anterior cruciate ligament replacement purposes. The risk of infections necessitates thorough sterilization procedures, and the allografts usually need to be stored prior to surgery. Classical mechanical tests have been performed with various types of tendons, however, tibialis anterior and peroneus longus tend to suffer the least biomechanical changes after irradiation. Only few results are available of the strain and creep behaviour of tendons, even though this information is necessary to provide suitable allografts. The aim of the present study is to analyze the effect of different tendon types (T-tibialis anterior, P-peroneus longus), sterilization methods (G-gamma irradiation of 21 kGy, E-electron beam irradiation of 21 kGy) and storage times (5 and 6 months) on the creep behavior, which is characterized by the strain at the end of the loading phase and creep deformation after static loading. Static creep tests were performed with 250 N load during 60 s. Deformation at the end of the loading phase of both tendons was significantly smaller after 5 months long storage than that after 6 months long storage. TE5 showed significantly less creep than group TE6, and TE6 significantly greater than PE6. The creep of TE5 was significantly lower than that of TG5. Based on the data, the peroneus longus sterilized by electron beam and stored deep frozen for 5 months is a better choice for anterior cruciate ligament reconstruction than tibialis anterior sterilized by gamma irradiation stored for 6 months.

A comparison of SanatMetal Sanat Swing and Zimmer NexGen® total knee implants: 10-year postoperative follow-up results.

OBJECTIVES: In this study, we present our 10-year postoperative follow-up results of Sanat Swing® and NexGen® total knee implants. PATIENTS AND METHODS: A total of 189 patients (93 males, 96 females; mean age: 68 years; range, 48 to 86 years) who underwent total knee replacement between January 2008 and September 2010 were retrospectively analyzed. A total of 105 patients (Group A) were implanted a cemented Sanat Swing knee prosthesis and 84 patients (Group B) were implanted a cemented NexGen knee prosthesis. Operation time, range of motion (ROM), pain level, Knee Society Score (KSS), distance of painless walking, and the ability to climb stairs were evaluated between the groups. RESULTS: The mean follow-up was 10.8 (range, 9.8 to 12.3) years. No significant difference was observed in the survival of the prostheses, ROM, pain level, KSS, walking distance, and in the ability to climb stairs between the two groups at 10 years. With an experienced team, the operation time was about 4 to 5 min shorter in the Sanat Swing implantation group. In selected cases, Sanat Swing was superior to the NexGen system; however, there was no statistically significant difference. Complication rates were also low and comparable between both groups. CONCLUSION: Based on the 10 years of follow-up evaluation, Sanat Swing total knee replacement system seems to yield comparable clinical results with the NexGen. Experiences with the operative technique and comparative evaluation, the Sanat Swing system is a safe and reliable alternative for total knee replacement, providing a user-friendly operative technique and shorter operation time.

Screening for preeclampsia in the first trimester of pregnancy in routine clinical practice in Hungary.

We aimed to evaluate the contribution of different factors in the Fetal Medicine Foundation algorithms for preeclampsia (PE) risk calculation during first-trimester screening in Hungary. We selected subjects for the nested case-control study from a prospective cohort of 2545 low-risk pregnancies. Eighty-two patients with PE and 82 gestational age-matched controls were included. Individual PE risk was calculated using two risk-assessing softwares. Using Astraia 2.3.1, considering maternal characteristics and biophysical parameters only, detection rates (DR) were 63.6% for early-PE and 67.6% for late-PE. When we added placenta associated plasma protein A (PAPP-A) to the risk calculation, DRs decreased to 54.5% and 64.8% respectively. Using Astraia 2.8.2 with maternal characteristics and biophysical parameters resulted in the DRs of 63.6% (early-PE) and 56.3% (late-PE). If we added PAPP-A to the risk calculation, DRs improved to 72.7% and 54.9%. The addition of placental growth factor (PlGF) did not increase detection rates in either calculation. In conclusion, using maternal characteristics, biophysical parameters, and PAPP-A, an acceptable screening efficacy could be achieved for early-PE during first-trimester screening. Since PlGF did not improve efficacy in our study, we suggest setting new standard curves for PlGF in Eastern European pregnant women, and the evaluation of novel biochemical markers.

Evaluation of clinical outcomes of cemented vs uncemented knee prostheses covered with titanium plasma spray and hydroxyapatite: A minimum two years follow-up.

OBJECTIVES: In this study, we introduce the SanatSwing cementless total knee prosthesis coated with a combination of titanium plasma spray and hydroxyapatite porous coating and compared its early results to the SanatSwing cemented knee prosthesis. PATIENTS AND METHODS: We compared 278 patients, who underwent total knee replacement between September 2012 and February 2017. A total of 142 patients (Group A; 78 male, 64 female, mean age 69±14) were implanted a cemented SanatSwing and 136 patients (Group B; 83 male, 53 female, mean age 59±10), a cementless SanatSwing knee prosthesis was implanted. Implant position and periprosthetic bone conditions were investigated over time on radiographs after a mean follow-up period of two years. Range of motion, pain level, distance of painless walk, and the ability to climb stairs were evaluated. RESULTS: Significant improvement was observed in both the cemented and uncemented groups when the preoperative scores were compared to the scores of their final visit, but we did not find any difference in measured scores between the cemented and uncemented group. Complication rates were low and almost similar in both groups without any significant difference. CONCLUSION: We used the combination of titanium plasma spray and the hydroxyapatite porous coating technique in cementless prostheses. Our results showed us that the novel SanatSwing cementless total knee prosthesis could be a great alternative to cemented total knee arthroplasty.

Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain.

Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) inhibitors induces strong antihyperalgesic effect during inflammatory pain. In this study we observed low level of DPP4 mRNA in the rat spinal dorsal horn in physiological conditions, which did not change significantly either in carrageenan-induced inflammatory or partial nerve ligation-generated neuropathic states. In naïve animals, microglia and astrocytes expressed DPP4 protein with one and two orders of magnitude higher than neurons, respectively. DPP4 significantly increased in astrocytes during inflammation and in microglia in neuropathy. Intrathecal application of two DPP4 inhibitors tripeptide isoleucin-prolin-isoleucin (IPI) and the antidiabetic drug vildagliptin resulted in robust opioid-dependent antihyperalgesic effect during inflammation, and milder but significant opioid-independent antihyperalgesic action in the neuropathic model. The opioid-mediated antihyperalgesic effect of IPI was exclusively related to mu-opioid receptors, while vildagliptin affected mainly delta-receptor activity, although mu- and kappa-receptors were also involved. None of the inhibitors influenced allodynia. Our results suggest pathology and glia-type specific changes of DPP4 activity in the spinal cord, which contribute to the development and maintenance of hyperalgesia and interact with endogenous opioid systems.

Does a different dose of gamma irradiation have the same effect on five different types of tendon allografts? - a biomechanical study.

INTRODUCTION: The goals of our study were to evaluate the biomechanical differences between five tendons and the changes in biomechanical properties caused by irradiation. METHODS: Achilles, quadriceps, semitendinosus + gracilis (STG), tibialis anterior (TA) and the peroneus longus (PL) were harvested from 30 donors. Group A contained 50 tendons without gamma irradiation. The groups were irradiated with a dose of 21 kGy (group B 50 tendons) and with a dose of 42 kGy (group C 50 tendons). The grafts were soaked in a radio-protectant solution and frozen at -80 °C. Cyclic loading tests were performed followed by load to failure tests. Young modulus of elasticity, maximum force, strain at tensile strength and strain at rupture were calculated. RESULTS: The Achilles tendons had significantly lower Young modulus than the TA (p = 0.0036) in group A. The Achilles showed significantly lower than PL (p = 0.000042) and TA (p = 0.00142) in group B and C. The quadriceps and the ST (p = 0.0037) provided poorer values than the TA (p = 0.0432) in group C. We found no difference in maximum loads among the tendons in group A. The maximum load of the Achilles and quadriceps showed better results than the PL (p = 0.0016), (p = 0.0018) and the STG (p = 0.0066), (p = 0.0019) in group C. The TA had similar results like the Achilles and quadriceps. DISCUSSION AND CONCLUSIONS: The vulnerability of gamma irradiation of TA was less than Achilles and quadriceps tendons.

Performance of a new HPV and biomarker assay in the management of hrHPV positive women: Subanalysis of the ongoing multicenter TRACE clinical trial (n > 6,000) to evaluate POU4F3 methylation as a potential biomarker of cervical precancer and cancer.

The ongoing Triage and Risk Assessment of Cervical Precancer by Epigenetic Biomarker (TRACE) prospective, multicenter study aimed to provide a clinical evaluation of the CONFIDENCE™ assay, which comprises a human papillomavirus (HPV) DNA and a human epigenetic biomarker test. Between 2013 and 2015 over 6,000 women aged 18 or older were recruited in Hungary. Liquid-based cytology (LBC), high-risk HPV (hrHPV) DNA detection and single target host gene methylation test of the promoter sequence of the POU4F3 gene by quantitative methylation-specific polymerase chain reaction (PCR) were performed from the same liquid-based cytology sample. The current analysis is focused on the baseline cross-sectional clinical results of 5,384 LBC samples collected from subjects aged 25 years or older. The performance of the CONFIDENCE HPV™ test was found to be comparable to the cobas® HPV test with good agreement. When applying the CONFIDENCE Marker™ test alone in hrHPV positives, it showed significantly higher sensitivity with matching specificity compared to LBC-based triage. For CIN3+ histological endpoint in the age group of 25-65 and 30-65, the methylation test of POU4F3 achieved relative sensitivities of 1.74 (95% CI: 1.25-2.33) and 1.64 (95% CI: 1.08-2.27), respectively, after verification bias adjustment. On the basis of our findings, POU4F3 methylation as a triage test of hrHPV positives appears to be a noteworthy method. We can reasonably assume that its quantitative nature offers the potential for a more objective and discriminative risk assessment tool in the prevention and diagnostics of high-grade cervical intraepithelial neoplasia (CIN) lesions and cervical cancer.

[The use of structural proximal tibial allografts coated with human albumin in treating extensive periprosthetic knee-joint bone deficiency and averting late complications. Case report]. / Humán albuminnal kezelt strukturális proximalis tibialis allograft alkalmazása kiterjedt térdízületi periprotetikus csonthiány esetén és a késoi szövodmény elhárítása.

The authors report the history of a 74-year-old patient who underwent surgical treatment for segmental knee-joint periprosthetic bone loss using structural proximal tibial allografts coated with serum albumin. Successful treatment of late complications which occurred in the postoperative period is also described. The authors emphasize that bone replacement with allografts is a physiological process that enables the stable positioning of the implant and the reconstruction of the soft tissues, the replacement of extensive bone loss, and also it is a less expensive operation. It has been already confirmed that treatment of lyophilised allografts with albumin improves the ability of bone marrow-derived mesenchymal stem cells to adhere and proliferate the surface of the allografts, penetrate the pores and reach deeper layers of the graft. Earlier studies have shown osteoblast activity on the surface and interior of the graft.

A rabbit model for studying degeneration and regeneration properties of young striated muscle at different distraction rates.

The present study evaluated the histological changes in the muscle tissue after limb lengthening in skeletally immature rabbits and assessed the effect of different lengthening rates on the regeneration and degeneration properties of striated muscle. Thirteen different lengthening protocols were applied on a total of 16 male domestic white rabbits divided into four groups. The histopathological changes were analysed by a semiquantitative method according to the scoring system of Lee et al. (1993). After evaluation of the five main degenerative parameters (muscle atrophy, internalisation of muscle nuclei, degeneration of the muscle fibre, perimysial and endomysial fibrosis, haematomas), it is evident that rabbits subjected to limb lengthening at a rate of 3.2 mm/day showed more degenerative changes than those limb-lengthened at 0.8 or 1.6 mm/day. Our study showed that the regenerative mechanisms were not endless. If the daily lengthening rate reached the 3.2 mm/day limit, the regenerating ability of the muscle decreased, and signs of degeneration increased significantly.

Structural changes in the lengthened rabbit muscle.

This study evaluated the histological changes in muscle tissue after limb lengthening in skeletally mature and immature rabbits and assessed the most vulnerable level of striated muscle. Twenty-three male domestic white rabbits, divided into six groups, were operated on and different lengthening protocols were used in the mature and immature rabbits. The histopathological changes were analysed by a semi-quantitative method according to the scoring system of Lee et al. (Acta Orthop Scand 64(6):688-692, 1993). After the evaluation of the five main degenerative parameters (muscle atrophy, muscle nuclei internalisation, degeneration of the muscle fibre, perimysial and endomysial fibrosis, haematomas), it is evident that the adults lengthened at a rate of 1.6 mm/day showed more degenerative changes than those lengthened at 0.8 mm/day. The adult 1.6 mm/day lengthened group presented significantly higher damage in the muscle and lower regenerative signs compared with the young 1.6 mm/day lengthened group, according to the summarised degenerative scores.

The humerus is the best place for bone lengthening.

The aim of this study was to examine the effectiveness of lengthening the humerus in children and young adults. Between 1984 and 2005, the Orthopaedic Department of Semmelweis University elongated 11 humeri (ten patients) for reasons of congenital hypoplasia (four cases), osteomyelitis (three cases), epiphyseolysis, growth plate closure after irradiation and obstetrical paralysis (one case each). The study cohort consisted of five females and five males, with an average age at the time of surgery of 17.8 years (range: 12-31 years). In every case, the lengthening was performed with a unilateral Wagner fixator. The lengthening protocol was 1 mm distraction daily (callotasis) after a 7-day latency period. The fixator was removed after total bone healing. Plate fixation or bone transplantation was not used. The average rate of lengthening was 6.2 cm (4.5-10.5 cm), and the achieved lengthening was 27% (range: 16-44%). The average healing index was 32 day/cm. One patient who suffered from temporary radial paresis, and temporary flexion contracture of the elbow was regarded as a complication following placement of the fixator. Based on our results, humeral shortening can effectively be treated with the unilateral Wagner fixator. The main difference between the original Wagner method and our approach is that we were able to leave the fixator in the humerus until total bony reconstruction so there was no need for plate fixation or bone transplantation.

The incidence of avascular necrosis of the healthy, contralateral femoral head at the end of the use of Pavlik harness in unilateral hip dysplasia.

We examined the incidence of avascular necrosis (AVN) of the healthy femoral head in unilateral hip dysplasia at the end of the use of the Pavlik harness. The evaluation of AVN was done with the help of standardised roentgenograms. Between 1974 and 1982, 1,064 dysplastic hips (869 children) were treated with the Pavlik harness at the Orthopaedic Department of Semmelweis University. Of these, 674 children who had unilateral hip dysplasia were chosen for this study. In the period of our investigation, ultrasonography was not yet used routinely, so in some cases the hip was mistakenly diagnosed as dysplastic. The average patient age was 3.2 months, and the average length of treatment was 4.9 months. We found no correlation between the appearance of AVN in the healthy hips at the end of treatment with the Pavlik harness and the age of the child at the start of treatment. On the other hand, there was a strong significant correlation between the appearance of AVN and the length of treatment.

Osteochondritis (Calvé's disease) of a vertebral body--a rare form of vertebra plana.

In 1925, Calvé described vertebra plana as an aseptic necrosis of bone involving a single vertebral body of the spinal column. This theory was set aside in 1954 by Compere, who concluded that vertebra plana is caused by eosinophilic granuloma and not by osteochondritis as suggested by Calvé. It has been well documented in literature that many factors other than eosinophilic granuloma can cause vertebra plana-like destruction of the vertebral body. However, the definition of the terms was not clear, and there was no consensus on whether to call these cases vertebra plana or not. Some authors did, some did not. Anyhow, no publication so far has reported on osteochondritis as a rare cause of vertebra plana. The case of a 12-year-old girl, presented here by the authors, suggests this explanation. Some important conclusions can be drawn from this regarding the nomenclature, the diagnosis, and the therapy.

Open adductor tenotomy in the prevention of hip subluxation in cerebral palsy.

We reviewed radiographs of 76 hips in 41 patients with cerebral palsy treated with open adductor tenotomy because of hip subluxation. The majority of patients suffered from spastic diplegia. The aim of our study was to evaluate the effect of adductor release on hip subluxation. We measured the centre-edge angle and migration percentage pre-operatively and 1 and 3 years post-operatively. We considered the results according to patients' age at time of surgery (younger or older than 4 years of age) and ability to walk. Children younger than 4 years of age had better results than children older than 4 years of age. In children without walking ability, more than half of the hips had further radiological subluxation. In children with walking ability, we observed stabilisation or improvement of femoral-head subluxation in more than three quarters of the cases.