Does radiological evaluation of endobutton positioning in the sagittal plane affect clinical functional results in single-bundle anterior cruciate ligament reconstruction?

INTRODUCTION: Sports injuries are increasing today due to the increased interest in sports. The most common injured knee ligament is the anterior cruciate ligament (ACL) in sport injuries. Accordingly, surgical treatment of the ACL is performed frequently. In this study, it was aimed to retrospectively evaluate whether the location of an endobutton on lateral knee radiography was effective on knee functional scores in patients who underwent ACL reconstruction. MATERIALS AND METHODS: One hundred thirty patients who underwent ACL reconstruction between January 2015 and February 2019 were identified. The patients were divided into three groups according to the location of the endobutton on lateral radiographs taken in the postoperative period. Group 1 patients were classified as anterior, group 2 as middle, and group 3 as posterior according to the location of the endobutton. Functional scoring, physical examination tests, comparative thigh diameter measurements, and single-leg hop tests were compared between the groups. It was evaluated as to whether there was a statistically significant difference between the groups. RESULTS: There were 38 patients in group 1, 63 patients in group 2, and 29 patients in group 3. The mean age was 29.1 in group 1, 29.1 in group 2, and 29.7 in group 3. The mean follow-up period of the patients was 18.4 months in group 1, 19.1 months in group 2, and 21.4 months in group 3. The average Lysholm score was 92.9 in group 1, 93.3 in group 2, and 91.7 in group 3. The mean modified Cincinnati scores were 27.0, 27.1, and 26.6, respectively, in the groups. The mean IKDC score of the subjective knee assessments was 92.5, 92.8, and 91, respectively, according to the groups. The average thigh atrophy value was 1 cm, 1 cm, and 1.2 cm, respectively, in the groups. In the single-leg hop test, 34 patients in group 1 jump to over 85% of the distance compared with the intact side, while 58 patients in group 2, and 23 patients in group 3 were successfully able to jump this distance. The effect of the placement of the endobutton in the anterior, middle or posterior was not statistically significant on functional scores and physical examination results. In patients with endobuttons in the middle, functional scores were found better than in those with anterior or posterior placement. CONCLUSIONS: No statistically significant differences were found in clinical functional results when comparing patients' endobutton location on femur. For this reason, surgical time should not be extended using unnecessary extra effort to change the orientation of the exit hole during surgery.

Phosphoproteomics of primary AML patient samples reveals rationale for AKT combination therapy and p53 context to overcome selinexor resistance.

Acute myeloid leukemia (AML) is a heterogeneous disease with variable patient responses to therapy. Selinexor, an inhibitor of nuclear export, has shown promising clinical activity for AML. To identify the molecular context for monotherapy sensitivity as well as rational drug combinations, we profile selinexor signaling responses using phosphoproteomics in primary AML patient samples and cell lines. Functional phosphosite scoring reveals that p53 function is required for selinexor sensitivity consistent with enhanced efficacy of selinexor in combination with the MDM2 inhibitor nutlin-3a. Moreover, combining selinexor with the AKT inhibitor MK-2206 overcomes dysregulated AKT-FOXO3 signaling in resistant cells, resulting in synergistic anti-proliferative effects. Using high-throughput spatial proteomics to profile subcellular compartments, we measure global proteome and phospho-proteome dynamics, providing direct evidence of nuclear translocation of FOXO3 upon combination treatment. Our data demonstrate the potential of phosphoproteomics and functional phosphorylation site scoring to successfully pinpoint key targetable signaling hubs for rational drug combinations.

Significance of Tip Apex Distance in Intertrochanteric Fracture femur managed with Proximal femoral nailing.

INTRODUCTION: Tip Apex distance (TAD) is well established method of prediction of outcome in intertrochanteric fractures managed by Dynamic Hip Screw. This retrospective study was done to assess the significance of Tip Apex Distance in the management of the intertrochanteric fractures by Proximal femoral nail. MATERIAL AND METHODS: The study was done in a tertiary care centre where 174 follow-up patients operated for intertrochanteric fractures with proximal femoral nail were included in the study. The radiological outcome of patients was assessed using the neck shaft angle, neck length and the offset whereas the functional status was assessed using the Harris hip score and the Lower extremity functional scoring system. These functional and radiological outcomes were compared with the TAD for any significant findings. RESULTS: The tip apex distance on the postoperative X-ray was found to be 22.93+3.88mm. The Lower Extremity Functional Score was found to be 70.71+8.153. The Harris Hip Score was found to be 85.408+9.586. Change in the neck length as compared to the uninjured hip was found to be 1.46+1.705. Change in the offset and neck shaft angle was 1.38+1.567 and -2.61+1.27 respectively. There were 8 cases of screw cut out and 8 cases of superficial infection. DISCUSSION: The Harris hip score and the LEFS increased with decreasing values of the Tip Apex distance. The Neck shaft angle, Neck length and the offset all decreased with the increase in the Tip Apex Distance. The Harris hip score and the LEFS decreased with the decrease in the Neck shaft angle, Neck length and the offset. On examining the 2 groups one with TAD <25mm and the other with TAD >25mm it was seen that both functionally and radiologically, the outcome was better in the group having TAD<25mm. CONCLUSION: This study indicates that the Tip Apex Distance can be used as a useful predictor of the outcome of the proximal femoral nail in intertrochanteric fractures. LEVEL OF EVIDENCE: IV.

Factors Influencing the Results in Matrix-Associated Autologous Chondrocyte Implantation: A 2 - 5 Year Follow-Up Study.

BACKGROUND: This study aimed to investigate the outcomes of matrix-associated autologous chondrocyte implantation (MACI) on the treatment of osteochondral lesions in the knee joint and to determine the factors affecting the functional results. METHODS: The study included 34 patients with a cartilage defect in the knee joint who were applied MACI® (GenzymeBiosurgery, Cambridge, Massachusetts, USA) technique between the years 2010 - 2015. The defect localizations and sizes, past surgeries were recorded. The clinical results were measured with Cincinnati and Lysholm scores. RESULTS: As a result of the repeated measures at postoperatively, it was found that the patients had increased Lysholm and Cincinnati functional scores in all follow-up periods (P = 0.0001). When the mean value of Lysholm and Cincinnati functional scores were assessed according to BMI group, no statistically significant difference was determined (P = 0.941 and P = 0.779). The measurements at 6 and 12 months of the follow-up indicated that the mean scores of the group with no concomitant pathologies were significantly higher than those of the group with concomitant pathologies. CONCLUSIONS: The MACI application provides good and stable outcomes for focal cartilage damage in young patients. In order to obtain significant results after autologous chondrocyte implantation, the selection of appropriate patients without concomitant pathologies is required.

Does anterolateral ligament rupture affect functional outcomes in patients who underwent an anterior cruciate ligament reconstruction?

BACKGROUND: Studies have shown that the anterolateral ligament contributes to knee stability. This study aims to compare the results of postoperative physical examinations, knee joint stability tests, and functional assessment tests of patients with intact anterolateral (AL) ligaments and patients with ruptured anterolateral (AL) ligaments. MATERIAL AND METHOD: This study consisted of 101 patients, with at least a 12-month follow-up period, who underwent an anterior cruciate ligament reconstruction between 2010 and 2016, and whose AL ligaments were evaluated by the radiologist with the preoperative and postoperative magnetic resonance images (MRI). Of these patients, 41 had intact AL ligament (Group 1) in MRI and other 60 had ruptured AL ligament (Group 2). Groups were compared according to postoperative physical examinations, knee joint stability tests, and functional assessment tests. RESULTS: The average Lysholm score of Group 1 was 94.9 (range: 81-100), and the score of Group 2 was 87.2 (range: 74-100). The modified Cincinnati score of Group 1 was 28.7 (24-30), while the score of Group 2 was 25.6 (21-30). The average IKDC subjective knee evaluation score of Group 1 was 91.9 (range: 83-100), and the score of Group 2 was 86.6 (range: 75-100). The average thigh atrophy value was 1.5 centimeters (cm) in Group 1 and 2.4 cm in Group 2. Thirty-three patients in Group 1 were able to jump over 85% of the distance in single-legged hop test compared to the intact side, while 16 patients in Group 2 were able to jump over this distance successfully. As a result of the analysis, it was determined that the Lysholm activity scoring results, the Modified Cincinnati scoring results, IKDC subjective knee evaluation results, two-cycle IKDC activity scale results, comparison of thigh diameters and the single-legged hop tests of two groups showed a statistically significant difference, and the results of the patients with intact AL ligaments who underwent an ACL reconstruction were found to be better (p < 0.05). No significant difference was found in other examinations and tests. CONCLUSION: Since the rupture of the AL ligament has negative effects on functional outcomes, we think that the reconstruction of the AL ligament in the same session with the ACL reconstruction or later will have a positive effect on functional outcomes.

PINES: phenotype-informed tissue weighting improves prediction of pathogenic noncoding variants.

Functional characterization of the noncoding genome is essential for biological understanding of gene regulation and disease. Here, we introduce the computational framework PINES (Phenotype-Informed Noncoding Element Scoring), which predicts the functional impact of noncoding variants by integrating epigenetic annotations in a phenotype-dependent manner. PINES enables analyses to be customized towards genomic annotations from cell types of the highest relevance given the phenotype of interest. We illustrate that PINES identifies functional noncoding variation more accurately than methods that do not use phenotype-weighted knowledge, while at the same time being flexible and easy to use via a dedicated web portal.

Therapeutic potential of human embryonic stem cells in type 2 diabetes mellitus.

AIM: To evaluate the safety and efficacy of human embryonic stem cells (hESCs) for the management of type 2 diabetes mellitus (T2DM). METHODS: Patients with a previous history of diabetes and its associated complications were enrolled and injected with hESC lines as per the defined protocol. The patients were assessed using Nutech functional score (NFS), a numeric scoring scale to evaluate the patients for 11 diagnostic parameters. Patients were evaluated at baseline and at the end of treatment period 1 (T1). All the parameters were graded on the NFS scale from 1 to 5. Highest possible grade (HPG) of 5 was considered as the grade of best improvement. RESULTS: Overall, 94.8% of the patients showed improvement by at least one grade of NFS at the end of T1. For all the 11 parameters evaluated, 54% of patients achieved HPG after treatment. The four essential parameters (improvement in glycated hemoglobin (HbA1c) and insulin level, and fall in number of other oral hypoglycemic drugs with and without insulin) are presented in detail. For HbA1c, 72.6% of patients at the end of T1 met the World Health Organization cut off value, i.e., 6.5% of HbA1c. For insulin level, 65.9% of patients at the end of T1 were able to achieve HPG. After treatment, the improvement was seen in 16.3% of patients who required no more than two medications along with insulin. Similarly, 21.5% of patients were improved as their dosage regimen for using oral drugs was reduced to 1-2 from 5. CONCLUSION: hESC therapy is beneficial in patients with diabetes and helps in reducing their dependence on insulin and other medicines.

Objective assessment of CNS function within 6 hours of spinal cord ischemia in rabbits.

PURPOSE: To develop a neurologic scoring (NS) system to objectively assess CNS function shortly after spinal cord ischemia. METHODS: Spinal cord ischemia was induced by temporarily clamping the infrarenal aorta in 27 rabbits anesthetized with isoflurane/N2O/O2 without muscle relaxants. Animals were divided ito group I, normothermic ischemia [I-a, 11 min (n=8); I-b, 12 min (n=8)], and group II, 60 min hypothermic ischemia targeted to II-a, 29.5°C (n=5), and II-i, 30.0°C (n=6). Postischemic neurologic function was scored from 0 to 6. RESULTS: Seventy-five percent of each group I subgroup ended with paraplegia. Function in the I-b group tended to be worse than in I-a (NS=1.7vs 1.9P>0.05). Hypothermia of 29.9±0.1°C protected partially (NS=2.8), whereas 29.4±0.1°C resulted in significantly higher NS, starting at 150 min (P<0.05vs IIi) with total recovery 5.5 hours (P<0.0001) post re-perfusion. CONCLUSIONS: Protection of the spinal cord from ischemia can be objectively quantitated by our system. Protection strategies can be compared within 6 h of the ischemia-insult.

Outcome analysis of functional endoscopie sinonasal surgery for paediatric rhinosinusitis using the Lund-Mackay-Kennedy scoring system.

There are very few indications for surgical management of chronic rhinosinusitis in children. This has been partly due to the fact that the definition of what qualifies as racalcitrant sinusitis in children is still obscure. There is also significant evidence in literature that surgery, especially radical surgery, on the nose and sinuses in children would result in some interference with the growth of the facio-maxillary skeleton. The advent of Functional Endoscopie sino-nasal Surgery ( F. E. S. S. ) in recent years has changed the philosophy of surgery for paediatric rhinosinusitis and has proven to be an effective choice of management in difficult cases. We persent here our experience and preliminary results with the use of FESS in nine children with sinonasal disorders including cystic fibrosis. The usefulness of the recently described Lund- mackay and Kennedy Scoring System for chronic rhinosinusitis in terms of symptom score, radiological score, endoscopie score and surgical score has been demonstrated.