Evaluation of posterior tibial slope relationship with common knee pathologies in pediatric and adolescent age groups in the Turkish population.

Anterior cruciate ligament rupture (ACLR), tibial eminence fracture (TEF), and Osgood-Schlatter disease (OSD) have been linked to a steep posterior tibial slope (PTS) in children and adolescents. This study aims to examine and compare these associations. 418 patients aged 8-18, 237 males and 181 females with knee pain between 2010 and 2019 were included and the patients belonged to the Turkish population. They consisted of ACLR (n = 47), TEF (n = 22), OSD (n = 51), and a control group (n = 298). The study and control groups were compared for PTS, sex, and age, with ACLR, TEF, OSD, retrospectively. The ACLR, OSD, and TEF groups had higher PTS values than the control group (P < 0.001). There was no significant difference in ACLR-OSD, ACLR-TEF, and OSD-TEF comparisons (P = 0.22, P = 0.99, and P = 0.99, respectively). PTS increase was linked to ACLR, TEF, and OSD in the multinomial regression analysis, (P < 0.001). Increase in PTS was associated with ACLR, TEF, and OSD for both males and females (independently of other factors; ACLR: P < 0.001, P < 0.001, OR: 1.59, OR: 2.63, TEF: P = 0.001, P < 0.001, OR: 1.98, OR: 1.44; OSD: P = 0.001, P < 0.001, OR: 1.49, OR: 1.28 for males and females respectively). ACLR, TEF, and OSD are associated with increased PTS in the pediatric and adolescent age groups, and there are differences between these pathologies in terms of the amount of PTS increase, age, and sex. Consideration of age and gender in pediatric and adolescent patients with increased PTS may be useful in predicting pathologies associated with increased PTS. Level of evidence: III retrospective comparative study.

Effectiveness of gonarthrosis treatment via intra-articular injections of linear vs. cross-linked hyaluronic acids.

OBJECTIVES: The study aimed to compare the outcomes of single-dose cross-linked hyaluronic acid and the linear regimen of three doses of HA knee injections among patients with gonarthrosis. PATIENTS AND METHODS: This single-center, retrospective study was conducted with 60 patients (47 females, 13 males; mean age: 57.9±4.29 years; range, 50 to 65 years) with Kellgren-Lawrence Grade 2 or 3 gonarthrosis between February 2020 and February 2022. Patients were either subjected to intra-articular cross-linked hyaluronic acid (n=30) or linear hyaluronic acid (n=30) injection treatments. Comprehensive assessments of the patients were conducted prior to the injections, as well as at three and six months after injection. The two injection groups were compared regarding the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Oxford Knee Score. RESULTS: Both injections showed a statistically significant improvement from baseline in both WOMAC and Oxford Knee Score at three and six months (p<0.001). There was no notable distinction in the alteration of WOMAC knee scores between the two injection types. However, a notable discrepancy was observed in the elevation of Oxford Knee Score among patients who received cross-linked knee injections compared to those who underwent linear hyaluronic acid knee injections, signifying a significant increase in the former group (p<0.001). CONCLUSION: The advantage of a single-dose administration of cross-linked HA knee injections, as opposed to the three-dose regimen required for linear hyaluronic acid, translates into reduced time and cost for the injection process. Moreover, this approach minimizes injection-associated discomfort for patients due to the singular dose administration.

Mid-term results of autologous matrix-induced chondrogenesis surgery with or without scaffolds for arthroscopic treatment of deep talus osteochondral lesions: A comparative study.

OBJECTIVES: This study aims to investigate the effectiveness of arthroscopic autologous matrix-induced chondrogenesis (AMIC) procedure with or without polyglycolic acid-hyaluronic acid (PGA-HA)-based cell-free scaffold (CFS) in Bristol Stage 4 and Stage 5 osteochondral lesion of the talus (OLT) ranging between 1.5 and 3 cm2 . PATIENTS AND METHODS: Between March 2018 and March 2021, a total of 47 patients with OLTs (29 males, 18 females; mean age: 22.8±2.3 years; range, 18 to 65 years) were retrospectively analyzed. The patients were divided into two groups based on the procedures applied. Patients in the first group (Group 1, n=23) underwent the AMIC procedure alone (curettage, microfracture, and grafting), while patients in the second group (Group 2, n=24) underwent AMIC procedure with PGA-HA-based CFS. The localization of the lesions was evaluated. All OLTs were diagnosed with preoperative radiography and magnetic resonance imaging (MRI). During the preoperative period, lesion stages were evaluated based on the Bristol staging system, and the postoperative results were evaluated based on the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring system. RESULTS: The mean follow-up was 36.2±5.6 months. In the early period, the three-month functional scores were comparable between the groups. While a significant increase was observed in the American Orthopaedic Foot and Ankle Society (AOFAS) scores from the mean preoperative of 62.71±4.44 points to the postoperative of 86.00±6.58 points in Group 1, a significant increase in the AOFAS score was observed from 65.28±7.91 points to 95.42±4.41 points in Group 2 at 12-month follow-up (p=0.016, p=0.011, respectively). The functional scores tended to progress after 12 months. Radiologically, a complete defect filling was observed in a mean of 10.5±2.7 months. No graft hypertrophy was recorded in any patients. The AOFAS and MOCART scores in Group 2 were found to be statistically significantly higher than that in Group 1 (p=0.034 for AOFAS 1/AOFAS 2 and p=0.006 for MOCART 1/MOCART 2). Overall, there was a positive, but weak, significant correlation between the final AOFAS scores and MOCART scores (r=0.347, p<0.001). CONCLUSION: Arthroscopic AMIC procedure in deep OLTs between 1.5 cm2 and 3 cm2 can yield a statistically significant improvement both clinically and radiologically; however, the use of a PGA-HA-based CFS in addition to this procedure can improve the clinical and radiological recovery.

First case of medullary osteogenic sarcoma of the pelvis: 12-year follow-up of reconstruction with hemipelvis allograft after resection.

A 45-year-old male patient with low-grade central osteosarcoma (LGCO) in the periacetabular region underwent wide resection, fresh frozen hemipelvis allograft reconstruction, and total hip prosthesis. To the best of our knowledge, this case is the first example of low-grade osteogenic sarcoma in flat bones. Aseptic loosening of the acetabular cup was observed 44 months after the operation, and it was revised with a constrained acetabular cup. Recurrent subluxation due to constraint ring failure and cup malposition was observed at 89 months after the revision surgery. Revision operation was performed with cage + non-constrained cup. Twelve years after the first operation, he is in exceptionally functional and disease-free condition. He can walk unlimited distances without pain. Radiographs show complete union at the junction of the allograft and disease-free bone.

The initial analysis of pediatric fractures according to the AO/OTA fracture classification and mechanisms of injuries.

BACKGROUND: The epidemiology of pediatric fractures has been changing timely, in a multifactorial fashion. The aim of this study was to put forward a recent 5-year epidemiological analysis of pediatric fractures, according to the current AO/OTA fracture classification, in the current decade of action for road safety. METHODS: A total of 3261 pediatric patients who were diagnosed with at least one fracture related with orthopedics and traumatology in a level-one trauma center were included in this retrospective and epidemiological descriptive study. The patients were grouped according to their ages as follows; <2, 2-5.9, 6-9.9, and 10-17.9. The fractures were examined according to the AO/OTA classification. RESULTS: A total of 3396 fractures were present in 3261 patients. The mean age of the patients was 9.8±4.6 (1-17). The number of patients according to the age groups was as follows; 28 (0.008%), 735 (22.53%), 863 (26.47%), and 1635 (50.99%), respectively. The most frequent three fractures according to the AO/OTA fracture classification were; 23 (radius/ulna distal 22.9%), 13 (humerus distal, 13.3%), and 7 (hand/carpal, 12%). About 68.8% and 31.2% of the patients were treated non-surgically and surgically, respectively. Overall mortality rate was 0.1%. CONCLUSION: To the best of our knowledge, this study represents the first analysis of pediatric fractures according to the AO/OTA classification, over a 5-year period. As a future prospect, further multicentric epidemiological studies are warranted to constitute a sustainable action plan for the prevention of major traumas.

Is there a predictive value of the preoperative neutrophil-lymphocyte ratio in terms of intensive care need in geriatric patients who underwent pertrochanteric fracture surgery?

BACKGROUND: Pertrochanteric fractures are serious health problem with an ever-increasing prevalence in elderly population. Potential post-operative intensive care need leads to delays in the timing of surgery due to the referral of patients to better equipped hospitals as well as the inability to arrange a reserved intensive care bed. The purpose of this study is to investigate whether pre-op-erative neutrophillymphocyte ratio (NLR) has predictive value in terms of post-operative intensive care need in geriatric patients who underwent surgery following pertrochanteric fractures. METHODS: A total of 535 patients aged 65 years and above with hip fractures who presented to the emergency service between 2017 and 2020 were retrospectively screened. Out of 535 patients, 317 patients who met the inclusion and exclusion criteria were included in the study. The screened patient population was divided into two groups as those followed in the post-operative intensive care unit (ICU) and those followed in the orthopedic ward. RESULTS: There were 190 patients (59.9%) who were followed in the orthopedic ward postoperatively and 127 (40.1%) patients followed in the ICU postoperatively. While the mean pre-operative NLR value of all patients was 6.57, the mean pre-operative NLR of the patients who were followed up postoperatively in the orthopedic ward was 5.85, and the mean NLR of those who were followed up in the ICU was 7.65. It was found that the admission NLR values of the ICU group patients were significantly higher compared to those of the orthopedic ward group (p<0.001) and also the cutoff value of NLR was calculated as 6.14. CONCLUSION: We believe that this objective, simple, cost-effective, and rapid marker can be used in combination with other parameters to predict ICU need to prevent surgical delays due to the lack of a reserved intensive care bed in the ASA 3 geriatric patient group with pertrochanteric fractures, whose intensive care need cannot be clarified, thereby reducing mortality and morbidity.

Outcomes of Planned Marginal and Wide Resection of Sarcomas Associated with Major Vascular Structures in Extremities.

Bone and soft tissue sarcomas of lower and upper extremities may sometimes be in close contact with neurovascular structures. In such cases, it is controversial that whether en bloc resection and vascular reconstruction to reach wider surgical margins or planned marginal resection with the help of adjuvant therapies should be preferred. This study aimed to determine surgical and oncological outcomes of planned marginal and wide resection of extremity sarcomas that are associated with major vascular structures in the extremities. The collected database of 54 patients treated by the same orthopedic and vascular surgeon for primary or locally recurrent soft and bone tissue sarcoma of extremities was retrospectively reviewed. Eligible subjects for this study were patients diagnosed with upper and lower extremity soft and bone tissue sarcomas that encased a maximum of 50% of the circumference of the major vascular structures, requiring limb-sparing resection. When microscopic positive (19 patients, 33.9%) and negative cases' (35 patients, 66.1%) surgical margins were compared, local recurrence, metastasis, amputation, and tumor type (soft/bone) parameters showed no statistically significant difference. When metastatic and non-metastatic patients were compared, it was shown that bone tumors metastasized more than soft tissue tumors (p = 0.001). However, there was no difference between metastasis and amputation, histopathology, grade, nerve involvement, surgical margins, or local recurrences. The mean survival was 1460.6 ± 137.4 days, and the 6-year mortality was 87.5%. Anesthetic and surgical complication rates may be higher since en bloc resection surgeries of large tumors with vascular reconstructions take a very long time. Therefore, we suggest marginal resection with sub-adventitial dissection in those locations and wide resection at other areas according to the surgeon's experiences about safe margin with the contribution of radiotherapy.

Does the pre-operative neutrophil-lymphocyte ratio have a predictive value in detecting infection in type 3 open tibia diaphysis fractures?

BACKGROUND: This retrospective study was aimed to investigate whether the pre-operative neutrophil-lymphocyte (N/L) ratio has a predictive value in terms of evaluating the development of infection in patients with type 3 open fractures of the tibia diaphysis. METHODS: A total of 72 patients with type 3 open tibia fractures who consulted to the emergency service at the Necmettin Er-bakan University Meram Faculty of Medicine, during the period between 2015 and 2020 were retrospectively examined. A total of 39 patients who underwent external fixator in the first treatment were included in the study. The information pertaining to the patients such as the patient demographic data, type of injury, wound cultures, and N/L rates during the pre-operative period were recorded. Patients were divided into two groups based on the presence of infection: Group 1 (12 patients) consisted of patients who had infec-tion, and Group 2 (27 patients) consisted of patients who had no infection. RESULTS: 34 (87.2%) of the patients were male and 5 (12.8%) were women. The mean age of these patients was 43.18±18.67 (19-80). Infection was detected in 12 (30.8%) out of 39 patients. Of these patients, 9 (75%) were monomicrobial, and 3 (25%) were polymicrobial. The most common mechanism of the injury was gunshot injury in 16 (41%) of all patients. However, there was no sig-nificant difference between the groups in terms of mechanism of injury (p=0.445). When all patients were examined in terms of N/L rates and presence of infection, there was no significant difference between Group 1 and Group 2 (p=0.976). CONCLUSION: Although N/L ratio of the blood in the pre-operative period has a predictive value for chronic diseases, we believe that it has no predictive value for detecting infection in patients with type 3 acute open tibia fractures.

Mid-term outcomes of hemipelvic allograft reconstruction after pelvic bone tumor resections.

OBJECTIVES: This study aims to evaluate survival of patients and implants, functions, and morbidity of surgical technique of reconstruction with a fresh-frozen massive pelvic allograft following a pelvic resection. PATIENTS AND METHODS: Between January 2009 and December 2016, a total of 19 patients (12 males, 7 females; mean age: 35.8±14.4 years; range, 10 to 53 years) who underwent reconstruction with fresh-frozen massive allograft after internal hemipelvectomy were retrospectively analyzed. Patients̓ age, sex, resection types, histopathology and grades, surgical margins, operative times, intraoperative blood loss, complications experienced during their treatment (infection, dislocation, implant failure, nonunion, local recurrence and metastasis), neoadjuvant and adjuvant therapies they received, and functional scores were revealed and analyzed in 10 years period. RESULTS: According to the Enneking and Dunham classification, two (10%) patients had type I resection only, six (32%) had type I-II, one (5%) had a type II resection, one (5%) had type II-III resection, three (16%) had type I-II-III resection, one (5%) had type I-IV resection, and five (26%) had type I-II-IV resection. The resection involved the acetabulum (type II) in all, but three patients. Several complications were seen in 12 patients, although seven patients had no complication. Pelvic resections had a high mortality rate in patients with malignant tumors and reconstruction with massive allograft had a high morbidity rate with susceptibility to many complications. Prolonged surgical time was found to be directly related to blood loss. Deep infection significantly worsened functional results. CONCLUSION: Despite the high complication rates seen in pelvic resections, massive pelvic allografts represent a valid option for reconstruction after resection of pelvic tumors, but due to the associated morbidity, patients should be carefully selected.

Discovery of Insulin Receptor Partial Agonists MK-5160 and MK-1092 as Novel Basal Insulins with Potential to Improve Therapeutic Index.

We have identified a series of novel insulin receptor partial agonists (IRPAs) with a potential to mitigate the risk of hypoglycemia associated with the use of insulin as an antidiabetic treatment. These molecules were designed as dimers of native insulin connected via chemical linkers of variable lengths with optional capping groups at the N-terminals of insulin chains. Depending on the structure, the maximal activation level (%Max) varied in the range of ∼20-70% of native insulin, and EC50 values remained in sub-nM range. Studies in minipig and dog demonstrated that IRPAs had sufficient efficacy to normalize plasma glucose levels in diabetes, while providing reduction of hypoglycemia risk. IRPAs had a prolonged duration of action, potentially making them suitable for once-daily dosing. Two lead compounds with %Max values of 30 and 40% relative to native insulin were selected for follow up studies in the clinic.

Functionally selective signaling and broad metabolic benefits by novel insulin receptor partial agonists.

Insulin analogs have been developed to treat diabetes with focus primarily on improving the time action profile without affecting ligand-receptor interaction or functional selectivity. As a result, inherent liabilities (e.g. hypoglycemia) of injectable insulin continue to limit the true therapeutic potential of related agents. Insulin dimers were synthesized to investigate whether partial agonism of the insulin receptor (IR) tyrosine kinase is achievable, and to explore the potential for tissue-selective systemic insulin pharmacology. The insulin dimers induced distinct IR conformational changes compared to native monomeric insulin and substrate phosphorylation assays demonstrated partial agonism. Structurally distinct dimers with differences in conjugation sites and linkers were prepared to deliver desirable IR partial agonist (IRPA). Systemic infusions of a B29-B29 dimer in vivo revealed sharp differences compared to native insulin. Suppression of hepatic glucose production and lipolysis were like that attained with regular insulin, albeit with a distinctly shallower dose-response. In contrast, there was highly attenuated stimulation of glucose uptake into muscle. Mechanistic studies indicated that IRPAs exploit tissue differences in receptor density and have additional distinctions pertaining to drug clearance and distribution. The hepato-adipose selective action of IRPAs is a potentially safer approach for treatment of diabetes.

The epidemiology of adult fractures according to the AO/OTA fracture classification.

BACKGROUND: The epidemiology of adult fractures has been changing timely, in a multifactorial fashion. The aim of this study was to put forward a recent 5-year epidemiological analysis of adult fractures, according to the current AO/OTA fracture classification, in the current decade of action for road safety. METHODS: 5324 adult patients who were diagnosed with at least one fracture related with orthopedics and traumatology in a level-one trauma center were included in this retrospective, epidemiological descriptive study. The patients were grouped according to their ages as; 18-35, 36-55, 56-69, and ≥70. The fractures were examined according to the AO/OTA classification. RESULTS: 5865 fractures were present in 5324 patients. The mean age of the patients was 48.6±21.5. The number of patients according to the age groups was as follows; 1947 (36.6%), 1636 (30.7%), 881 (16.5%), and 860 (16.2%), respectively. The most frequent three fractures according to the AO/OTA fracture classification were; 7 (hand 19.6%), 23 (distal forearm, 12.1%), and 8 (foot, 11.8%). About 54.4% and 45.4% of the patients were treated non-surgically and surgically, respectively. About 0.2% of the patients preferred an alternative treatment. Overall mortality rate was 0.4%. CONCLUSION: To the best of our knowledge, this study represents the first analysis of adult fractures according to the AO/OTA classification, over a 5-year period. As a future prospect, further multi-centric epidemiological studies are warranted to constitute a sustainable action plan for the prevention of major traumas.

Adolescent pelvic chondrosarcoma, surgical treatment, and unusual reconstruction with pedestal conic cup (LUMiC®): A case report.

An 18-year-old male patient was diagnosed pelvic chondrosarcoma histopathologically. Hip joint involvement was detected. No metastasis or neurovascular invasion was seen. Type I+II pelvic resection and hip reconstruction were planned with pedestal cup (LUMiC®) and proximal femur tumor prosthesis. Surgery was performed in lateral decubitus position with extensive triradiate incision. Pelvic wide resection was performed. At the second year of follow-up, implant failure was detected and patient was revised with same pedestal cup. Axial stability was supported by a L5 screw and connector from L5 vertebrae to LUMiC® prosthesis. Except the implant failure, no oncological complication or infection was observed during the final 36th month follow-up.

In Situ Forming Injectable Thermoresponsive Hydrogels for Controlled Delivery of Biomacromolecules.

Due to their relatively large molecular sizes and delicate nature, biologic drugs such as peptides, proteins, and antibodies often require high and repeated dosing, which can cause undesired side effects and physical discomfort in patients and render many therapies inordinately expensive. To enhance the efficacy of biologic drugs, they could be encapsulated into polymeric hydrogel formulations to preserve their stability and help tune their release in the body to their most favorable profile of action for a given therapy. In this study, a series of injectable, thermoresponsive hydrogel formulations were evaluated as controlled delivery systems for various peptides and proteins, including insulin, Merck proprietary peptides (glucagon-like peptide analogue and modified insulin analogue), bovine serum albumin, and immunoglobulin G. These hydrogels were prepared using concentrated solutions of poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PLGA-PEG-PLGA), which can undergo temperature-induced sol-gel transitions and spontaneously solidify into hydrogels near the body temperature, serving as an in situ depot for sustained drug release. The thermoresponsiveness and gelation properties of these triblock copolymers were characterized by dynamic light scattering (DLS) and oscillatory rheology, respectively. The impact of different hydrogel-forming polymers on release kinetics was systematically investigated based on their hydrophobicity (LA/GA ratios), polymer concentrations (20, 25, and 30%), and phase stability. These hydrogels were able to release active peptides and proteins in a controlled manner from 4 to 35 days, depending on the polymer concentration, solubility nature, and molecular sizes of the cargoes. Biophysical studies via size exclusion chromatography (SEC) and circular dichroism (CD) indicated that the encapsulation and release did not adversely affect the protein conformation and stability. Finally, a selected PLGA-PEG-PLGA hydrogel system was further investigated by the encapsulation of a therapeutic glucagon-like peptide analogue and a modified insulin peptide analogue in diabetic mouse and minipig models for studies of glucose-lowering efficacy and pharmacokinetics, where superior sustained peptide release profiles and long-lasting glucose-lowering effects were observed in vivo without any significant tolerability issues compared to peptide solution controls. These results suggest the promise of developing injectable thermoresponsive hydrogel formulations for the tunable release of protein therapeutics to improve patient's comfort, convenience, and compliance.

Regenerative effects of hyperbaric oxygen therapy and platelet-rich plasma on the osteochondral defects of rats.

OBJECTIVES: This study aims to investigate the effects of hyperbaric oxygen (HBO) therapy and platelet-rich plasma (PRP) on the regeneration of osteochondral defects of the rats, and the synergistic effect of this combined treatment. MATERIALS AND METHODS: This randomized, controlled, and interventional animal study was conducted between May 2014 and August 2014 Osteochondral regeneration was evaluated in four treatment groups (control, PRP, HBO, and HBO+PRP groups) at the 30th day after iatrogenic injury. Thirty-two female Wistar albino rats (weighing 248-305 g) underwent arthrotomy and osteochondral surgery on left knees. The regenerations of defects were then examined histologically by the modified version of O'Driscoll score. RESULTS: Groups that were treated with either HBO or PRP alone regenerated significantly better than the control group (p=0.01), while no significant difference was found between the HBO- and PRP-treated groups (p>0.05). The defects in group 4 (treated with both HBO and PRP) regenerated significantly better than the control group, the HBO-treated group alone, and the PRP-treated group alone (p=0.01). CONCLUSION: The results of this study showed a synergistic effect of HBO and PRP on knee cartilage regeneration. However, the possible underlying mechanisms should be the subject of future researches. The aggregation and activation of growth factors released from platelets whose activation is increased in the hyperbaric environment may explain this effect. This may result in a better regeneration than the effect of PRP or HBO alone.

NMR Assessment of Therapeutic Peptides and Proteins: Correlations That Reveal Interactions and Motions.

NMR measurements of rotational and translational diffusion are used to characterize the solution behavior of a wide variety of therapeutic proteins and peptides. The timescales of motions sampled in these experiments reveal complicated intrinsic solution behavior such as flexibility, that is central to function, as well as self-interactions, stress-induced conformational changes and other critical attributes that can be discovery and development liabilities. Trends from proton transverse relaxation (R2 ) and hydrodynamic radius (Rh ) are correlated and used to identify and differentiate intermolecular from intramolecular interactions. In this study, peptide behavior is consistent with complicated multimer self-assembly, while multi-domain protein behavior is dominated by intramolecular interactions. These observations are supplemented by simulations that include effects from slow transient interactions and rapid internal motions. R2 -Rh correlations provide a means to profile protein motions as well as interactions. The approach is completely general and can be applied to therapeutic and target protein characterization.

Site-Selective Synthesis of Insulin Azides and Bioconjugates.

A synthetic method to access novel azido-insulin analogs directly from recombinant human insulin (RHI) was developed via diazo-transfer chemistry using imidazole-1-sulfonyl azide. Systematic optimization of reaction conditions led to site-selective azidation of amino acids B1-phenylalanine and B29-lysine present in RHI. Subsequently, the azido-insulin analogs were used in azide-alkyne [3 + 2] cycloaddition reactions to synthesize a diverse array of triazole-based RHI bioconjugates that were found to be potent human insulin receptor binders. The utility of this method was further demonstrated by the concise and controlled synthesis of a heterotrisubstituted insulin conjugate.