Selective Dorsal Scapular Nerve and Long Thoracic Nerve Blocks for Rescue Analgesia in Scapulothoracic Arthrodesis Surgery: A Case Report.

Scapulothoracic arthrodesis (STA) surgery is performed to stabilize the scapula in patients with facioscapulohumeral dystrophy (FSHD). Postoperative pain could be a major problem even while using erector spinae plane block (ESPB). We performed a preoperative ESPB with an intraoperative ESPB catheter, but rescue analgesia was needed for pain in the periscapular area in the postoperative period. The patient's pain score was reduced by applying an ultrasound-guided dorsal scapular nerve (DSN) and long thoracic nerve (LTN) block. Selective DSN and LTN blocks can be effective in enhancing postoperative analgesia in STA surgery.

In silico analysis of rib force distribution in postscapulothoracic arthrodesis model.

Scapulothoracic arthrodesis (STA) is carried out by fixing the scapula to thoracic ribs which in turn allows the patient suffering from Facioscapulohumeral Muscular Dystrophy to carry out shoulder-joint dependent activities of daily living. A biomechanical analysis of this procedure has not been conducted in the literature and, for the first time, this study investigates the finite element calculated glenohumeral-applied load distributions on ribs by creating a post-STA model. Three loading directions on the glenohumeral joint are designated: anterior-posterior, superior-inferior, and lateral-medial. Reaction forces on the ribs are calculated based on the glenoid force percent. Simulations are repeated by removing a singular rib contact to observe the change in force distributions in the case of missing levels or failed bonding as well as the impact of clavicle osteotomy. Total load distribution is observed highest at T2 followed by T3 and T6. In the T2 missing scenario, total loads on T3 and T4 increase. In the T4 missing case, the most affected level is T3. In the T6 missing scenario, total loads on T5 and T7 increase. In the clavicular osteotomy scenario, all levels' loads increase; the highest is recorded in T7 by 460%, followed by T5, T4, T2, T6, and T3. While all levels contribute to fixation strength, T2 is subjected to the highest loads, and, in the missing level scenarios, the loads are tolerated sufficiently by the remaining levels. Missing T4 scenario has the least effect on the system, which is interpreted as potentially the only skippable level of fixation. Clavicular osteotomy has the highest effect on the arthrodesis site.

Intraoperative fluoroscopic safety assessment of femoral head implants with 3-dimensional risk parameters to minimize cut-out.

OBJECTIVE: This study aimed to introduce a method to extract the 3-dimensional spatial position of the femoral head implant from 2-dimensional fluoroscopic projections, allowing surgeons to assess fixation much more accurately and prevent cut-out complications in proximal femoral nailing. METHODS: To define a safety region for the tip in the femoral head, a novel 3-dimensional distance-based risk parameter called TSD3D was introduced. An intersection algorithm was developed that solely takes the fluoroscopic anteroposterior and lateral distances to reveal the 3-dimensional location of the screw or Kirschner wire tip, enabling the utilization of the 3-dimensional parameter. Orthogonal per- spectives of 6 femur proximal bone substitutes with randomly inserted Kirschner wires were imaged under fluoroscopy. The developed algorithm was used to calculate the implant tip location in 3-dimensional from 2-dimensional images for each case. Algorithm accuracy was validated with the computed tomography-obtained 3-dimensional models of the same femur substitutes. RESULTS: The newly introduced risk parameter successfully visualizes 3-dimensional safety regions. Utilizing the 2-dimensional fluoro- scopic distances as inputs to the algorithm, the 3-dimensional position of the implanted Kirschner wire tip is calculated with a maximum of 9.8% error for a single Cartesian-coordinate measurement comparison. CONCLUSION: By incorporating the newly introduced 3-dimensional risk parameter, surgeons can more precisely evaluate the position of the implant and avoid cut-out complications, instead of relying solely on misleading 2-dimensional fluoroscopic projections of the femoral head.

Functional outcomes of pediatric true and equivalent Monteggia fractures - Review of the literature.

BACKGROUND: This study aims to describe the functional outcome of true and equivalent Monteggia fracture-dislocations in the pediatric population. We also provided a review of the literature about the treatment options. METHODS: Five surgically and three conservatively treated patients were identified who were treated in 2009-2021. The study pop-ulation consisted of six female and two male patients. The mean age at the time of treatment was 7. The mean follow-up time was 55 months (range, 12-128). The Mayo Elbow Performance Score and the Oxford Elbow Score were used for outcome evaluation. Range of motion and grip strengths were also evaluated. RESULTS: There were two Bado type 1 and six Monteggia equivalent injuries. Closed reduction and casting were utilized for the two Bado type 1 injuries as the initial treatment. However, one had a radial head re-dislocation and had to be treated operatively. This patient had a radial head re-dislocation after the surgery and was followed up conservatively. Three Monteggia equivalent injuries were treated with closed reduction and casting, with no complications. One patient had a radial head anterior dislocation with plastic deformation of the ulna, and this patient was managed with CORA-based corrective ulnar osteotomy. For Monteggia injuries, the main treatment objective is to restore the ulnar length. Bilateral computed tomography imaging with 3D reconstruction can be utilized in preoperative planning of Monteggia fracture-dislocations to customize the treatment. Close observation is essential to detect radial head subluxation, which needs early intervention before irreversible changes occur. CONCLUSION: The true/equivalent Monteggia fractures' main treatment goal is to restore the ulnar length. Conservative treatment, with a close follow-up, is the first option if closed reduction can be achieved. If closed reduction is not possible, careful preop-erative planning and early rehabilitation are key to success for management of Monteggia fractures.

Erector Spinae Plane Block for Scapulothoracic Arthrodesis for Facioscapulohumeral Dystrophy Patients: A Case Series.

Facioscapulohumeral dystrophy (FSHD) typically affects the periscapular muscles, resulting in scapular winging. Scapulothoracic arthrodesis (STA) stabilizes the scapula to provide better movement for these patients. Analgesia regimen for FSHD patients who received a single-shot erector spinae plane block (ESPB) and a catheter at the area were retrospectively analyzed in this study. Patients were asked to rate their pain postoperatively and only 5 of 10 patients needed rescue analgesic. No complications occurred. Our experience suggests that continuous ESPB may be helpful for providing analgesia in FSHD patients undergoing STA.

Cognitive functions in episodic vestibular disorders: Meniere's disease and vestibular migraine.

BACKGROUND: Cognitive deficits have been defined in patients with bilateral and unilateral vestibular loss. OBJECTIVE: To investigate cognitive functions in patients with episodic vestibular disorders. METHODS: Nineteen patients with Meniere's disease (MD), 19 patients with vestibular migraine (VM) and 21 age and education matched healthy controls were studied. Mini Mental State Examination assessing global mental status, Reading Span Test and the Stroop Test evaluating working memory, cognitive processing, reading comprehension and attention, Trail Making Test and Benton's Judgment of Line Orientation Test investigating visual processing, visuospatial skills, processing speed were used. Beck depression and anxiety inventories were given to evaluate the emotional status. RESULTS: Cognitive test results of the MD and VM patients were not significantly different from the healthy controls (p > 0.05) as well as Beck depression scores (p = 0.14). Beck anxiety scores showed significant difference (p = 0.003). VM patients had significantly higher scores than the healthy controls (p = 0.002) on pairwise comparisons. The scores of the MD patients did not reach statistical significance (p = 0.15). CONCLUSION: Episodic vestibular disorders like MD and VM without inter-ictal vestibular deficits do not seem to be associated with cognitive impairment. Patients with VM have significantly higher anxiety scores than the healthy controls and MD patients.

Comparison of anterior suprascapular nerve block versus interscalane nerve block in terms of diaphragm paralysis in arthroscopic shoulder surgery: a prospective randomized clinical study.

OBJECTIVE: This prospective, randomized study aimed to compare anterior suprascapular nerve block versus interscalene block in terms of diaphragm paralysis in arthroscopic shoulder surgery. METHODS: Fifty-two patients undergoing shoulder arthroscopy surgery were prospectively randomly assigned to interscalene block (n=25) or anterior suprascapular nerve block groups (n=27) (each group receiving 5 mL, 0.5% bupivacaine). The ipsilateral diaphrag matic excursion was assessed in all patients using ultrasound imaging before (baseline), 30 minutes, and 24 hours after block completion. Pain scores were recorded 1 hour preoperative, 30-60 minutes in the postoperative recovery unit, and at 6 and 24 hours postoperatively. RESULTS: No complete paralysis was observed in either treatment group. The incidence of a partial decrease in diaphragm movements was significantly lower in the anterior suprascapular nerve block than in the interscalene block group (1 vs. 21 patients) (P < .01). Twenty-six patients in the anterior suprascapular nerve block and 4 in the interscalene block group had less than a 25% decrease in hemidiaphrag matic movements, 30 minutes after the blockade. Pain scores were similar in the 2 groups. However, mean pain scores at 24 hours post operatively were significantly higher in the interscalene block than in the anterior suprascapular nerve block group (P < .05). Time to first pain post-block was significantly longer in the anterior suprascapular nerve block compared to the interscalene block group (677.04 ± 52.17 minutes vs. 479.2 ± 99.74 minutes, P < .05). CONCLUSION: Anterior suprascapular nerve block and interscalene block both appear to be clinically effective in providing postoperative analgesia for patients undergoing arthroscopic shoulder surgery under general anesthesia. However, the time to first pain is significantly longer with anterior suprascapular nerve block. Pain scores at 24 hours postoperatively were significantly lower in the anterior supra scapular nerve block compared to the interscalene block group. Diaphragmatic movements after anterior suprascapular nerve block were also better preserved at both 30 minutes after the block and 24 hours after surgery. LEVEL OF EVIDENCE: Level I, Therapeutic Study.

Turkish version of the patient-based Constant-Murley Score: Its cross-cultural adaptation, validity, reliability and comparison with the clinician-based version.

Objectives: The aim of this study was to translate, cross-culturally adapt the patient-based Constant-Murley Score (p-CMS), assess its validity, reliability, and compare it with the clinician-based CMS (c-CMS). Patients and methods: This cross-sectional study included a total of 51 shoulders of 46 patients (22 males, 24 females; mean age: 49±10 years; range, 29 to 70 years) with shoulder pain between December 2015 and July 2016. After translation of p-CMS, each participant was asked to complete the final Turkish version of the p-CMS. The c-CMS was assessed by a physiatrist who was blinded to the p-CMS. Retest of the p-CMS was performed in patients (n=15) who did not receive any treatment between two visits (Days 3 to 5). Results: A total of 51 shoulders (n=5 bilateral shoulder pain) were tested. Strength, subjective, objective, and total scores were significantly different between the p-CMS and c-CMS (p<0.001). Pain scores of the c-CMS and p-CMS revealed similar results with 95% limits of agreement of -3.81 and 4.81. Weighted kappa statistics demonstrated that the levels of agreement ranged between 0.343 and 0.698 in subjective and between 0.379 and 0.515 in objective components. For test-retest reliability of the p-CMS, intraclass correlation coefficient values ranged between 0.838 and 0.995. Conclusion: The Turkish version of the p-CMS has internal consistency and test-retest reliability to evaluate shoulder function in Turkish patients with shoulder pathologies. Considering the differences in test protocols and scoring methods of c-CMS and p-CMS, their interchangeable use is not supported.

Management of scapular dysfunction in facioscapulohumeral muscular dystrophy: the biomechanics of winging, arthrodesis indications, techniques and outcomes.

Facioscapulohumeral muscular dystrophy (FSHD) is a common hereditary disorder which typically results in scapular winging due to wasting of the periscapular muscles affected by this condition. Scapulothoracic arthrodesis (STA) is the current surgical treatment for FSHD patients with severe winging and preserved deltoid muscle. There are several different techniques in the literature such as multifilament cables alone and cable or cerclage wires combined with single or multiple plates. We prefer cables without plates as it provides independent strong fixation points and strongly recommend utilization of autograft. The functional results of studies report that regardless of the technique used, shoulder elevation and thus quality of life is improved, as shown with outcome scores. There are several complications associated with STA. Pulmonary complications are common and usually resolve spontaneously. Meticulous surgical technique and effective postoperative analgesia may reduce the incidence. Scapular complications which are associated with the fixation may be encountered in the early or late period, which are related to the learning curve of the surgeon. In conclusion, STA is a reliable solution to a major problem in FSHD patients that helps them maintain their activities of daily living until a cure for the disease is found. A successful result is strongly dependent on patient selection, and a multidisciplinary team of neurologists, geneticists and orthopaedic surgeons is required to achieve good results.

Corticosteroid-Refractory Myositis After Dual BRAF and MEK Inhibition in a Patient with BRAF V600E-Mutant Metastatic Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma is a rare malignancy, which is rich in actionable alterations. Genomic aberrations in the mitogen-activated protein kinase (MAPK) pathway are common, and BRAF exon 15 p.V600E mutations are present in 5-7% of biliary tract cancers (BTC). Dual inhibition of BRAF and MEK has been established for BRAF-mutated melanoma and lung cancer, and recent basket trials have shown efficacy of this combination in BRAF V600E-mutant BTCs. Here, we report on a patient with BRAF exon 15 p.V600E mutant metastatic intrahepatic cholangiocarcinoma who was started on BRAF and MEK inhibition with vemurafenib and combimetinib. Shortly thereafter, he developed debilitating myositis, which was refractory to corticosteroids, requiring therapeutic plasma exchange and intravenous immunoglobulin. We also review BRAF as a target in BTCs, relevant clinical trials, and adverse events associated with BRAF and MEK inhibition.

Intraosseous calcific tendinitis of the rotator cuff yields similar outcomes to those of intratendinous lesions despite worse preoperative scores.

PURPOSE: To evaluate the surgical outcomes of arthroscopic removal of intraosseous deposits in patients with intraosseous calcific tendinitis of the rotator cuff. METHODS: This study involved a retrospective review of 96 patients operated on from 2004 to 2019. Patients were divided into two groups according to the location of calcific deposits. Group I had pure tendinous involvement (n = 71), and Group II had tendinous and intraosseous involvement (n = 25). The mean follow-up time was 6.4 ± 3.9 years. There were 71 patients (46 women, 25 men) in Group I, and the mean age was 49.3 ± 8.2 years (range 30-65 years). In group II, there were 25 patients (18 women, 7 men); the mean age was 47.3 ± 11.2 years (range 28-70 years). RESULTS: The mean preoperative VAS pain score was 8.8 ± 1.4 in Group I compared to 9.5 ± 0.5 in group II (p = 0.017). The median preoperative Constant and Oxford scores were 42 (20-65) and 22 (8-34) in Group I and 25.5 (22-46) and 10 (8-16) in group II, respectively (p < 0.001). There was no difference in postoperative pain scores (Group I: 0.7 ± 1.6 and group II: 0.5 ± 0.6, p = 0.926), Constant scores [Group I: 100 (80-100) and group II: 100 (90-100), (n.s).] and Oxford scores [Group I: 48 (28-48) and group II: 46.5 (4-48), (n.s.)] between the two groups. The number of preoperative injections was higher in Group II (p = 0.05). There was no correlation between the size of the soft tissue calcific deposit and the preoperative pain, Constant, and Oxford scores (n.s.). CONCLUSION: Arthroscopic debridement of calcific tendinitis with intraosseous involvement is a safe and effective treatment method similar to that of pure tendinous involvement. LEVEL OF EVIDENCE: III.

A novel lower bound for tip-apex distance.

PURPOSE: The cut-out of the cephalomedullary nail is among the most common post-surgery complications for intertrochanteric fractures. As a risk predictor, a tip-apex distance (TAD) below 25 mm, observed from orthogonal fluoroscopic views, is recommended in the literature. This study aims to demonstrate that TAD < 25 mm is a mathematically insufficient risk definition and to complement the TAD upper bound with an appropriate lower bound, with the introduction of a novel distance parameter, TADX, based on the orthogonal projection of the nail tip on the central femoral midline. METHOD: Through a mathematical simulation software, all the possible points that lie inside the AP and lateral views of the proximal femoral hemisphere are utilized to create a 3D grid that is sorted into geometrically safe and risk-bearing regions. Extending this methodology, TAD < 25 mm, 10 mm < TAD < 25 mm, and the ideal tip position volumes are simulated. Finally, intersection volumes are created by a combination of different candidate lower TADX bounds and TAD < 25 mm upper bound to determine satisfactory TADX limits. RESULTS: Simulation of TAD-bound zones exposed that TAD is only a mathematically suitable parameter for defining the upper boundary but not the lower boundary for the optimal region. However, using a TADX lower limit creates a 3D volume that is much closer to the optimal tip region volumetrically and can still be as quickly calculated from 2D AP and lateral views. CONCLUSIONS: According to the mathematical simulations, the use of a TADX lower bound of 9 mm for small, 7.5 mm for medium, and 7 mm for large femoral heads in conjunction with a TAD upper bound of 25 mm is suggested.

Translation, cross-cultural adaptation, reliability, and validity of Turkish version of the university of California Los Angeles (UCLA) shoulder scale into Turkish.

PURPOSE: To translate and culturally adapt the University of California Los Angeles (UCLA) shoulder scale into Turkish (T-UCLA) and determine its psychometric properties. MATERIAL AND METHODS: The UCLA scale was translated into Turkish using Beaton guidelines. Ninety-one patients (46 male; mean age: 46.0 ± 13.7 years) with shoulder disorders completed T-UCLA and American Shoulder and Elbow Score (ASES), Simple Shoulder Test (SST) and 36-Item Short Form (SF-36). Test-retest reliability was tested in 50 patients at a mean of 5.2 ± 2.2 days after initial assessment. Validity was evaluated in 91 patients, and correlations between ASES, SST and SF-36 were analyzed. Responsiveness was assessed in 33 patients who underwent arthroscopic rotator cuff repair with a mean follow-up of 12.8 ± 0.5 months. RESULTS: Test-retest reliability of overall T-UCLA, pain and function subscales were 0.96, 0.94 and 0.86, respectively. The correlation coefficients between T-UCLA and SST and ASES were r = 0.752 and r = 0.783, respectively (p < 0.001). The highest correlations between T-UCLA and SF-36 were observed in physical functioning (r = 0.64) and bodily pain subscales (r = 0.66). No ceiling or floor effect observed. Overall and subscales of T-UCLA were highly responsive (ES = 3.22-4.31). CONCLUSION: T-UCLA has sufficient reliability and validity similar to original and translated versions. T-UCLA is responsive in patients who underwent rotator cuff repair.Implications for rehabilitationIn this study, Turkish version of the UCLA was found to be a reliable and valid outcome measure in patients with various shoulder pathologies.Turkish version of the UCLA is a very responsive tool in patients with who underwent arthroscopic repair of rotator cuff tears.

Patients without re-dislocation in the short term after arthroscopic knotless Bankart repair for anterior shoulder instability may show residual apprehension and recurrence in the long term after 5 years.

HYPOTHESIS: The aim of this study was to report the long-term results, residual instability, and recurrence rate of arthroscopic Bankart repair surgery without a re-dislocation event in the first 5 years. METHODS: We performed a retrospective analysis of Bankart repairs performed in a single center, by a single surgeon, with a minimum of 5 years' follow-up. Patients without a re-dislocation in the first 5 years of surgery were included. Patients who underwent open repair, those who underwent revision surgery, and those with critical glenoid bone loss were excluded. A total of 68 shoulders in 66 patients (51 male and 15 female patients) were included. Patients were analyzed in 2 domains: (1) failures defined as re-dislocation and (2) failures defined as apprehension and re-dislocation combined (residual instability). Clinical outcomes were assessed using shoulder range of motion, the American Shoulder and Elbow Surgeons score, and the Western Ontario Shoulder Instability Index (WOSI) score. Pain, residual apprehension, re-dislocations, and additional surgical procedures were recorded. RESULTS: The mean age of patients was 31.16 (range, 16-60 years), and the mean follow-up duration was 8.42 ± 2.1 years. The median number of dislocations was 3 (range, 1-20), and the median time from first dislocation to surgery was 16 months (interquartile range, 3-100.5 months). Five patients reported re-dislocations (7.4%) with a mean period of 6.54 ± 2.5 years (range, 5-10.8 years). Seven patients without re-dislocations and 2 patients with re-dislocations reported residual apprehension. Mean shoulder elevation and mean external rotation were 161.3° ± 12.4° and 39.2° ± 11°, respectively. The mean visual analog scale, American Shoulder and Elbow Surgeons, and WOSI scores were 0.5 ± 1.4, 91 ± 11.9, and 88 ± 12.1, respectively. Age was similar in patients with stable shoulders and those with shoulders with re-dislocation or residual instability. The WOSI score was lower in patients with re-dislocation and residual instability (P = .030 and P = .049, respectively). CONCLUSIONS: Arthroscopic Bankart repair is a successful surgical option for anterior shoulder instability. The 7.4% re-dislocation rate after 5 years indicates there may be a deterioration of capsulolabral repair in certain patients. The long-term failure pattern may be underestimated in short- to mid-term projections.

Cemented radial head arthroplasty: Does radiographic loosening have an effect on clinical and functional outcomes? Average 10 years' results.

PURPOSE: The aim of this study was to evaluate the possible effect of radiographic loosening on clinical and functional outcomes, while presenting the mid-term radiographic and functional outcomes of cemented, monopolar RHA applied to patients with comminuted radial head fractures. METHODS: We performed a retrospective study by evaluating the records of patients who were diagnosed in a single center with radial head fractures between 2001 and 2013. Twenty-six patients with comminuted radial head fractures with a mean age of 48.9 and a mean follow-up time of 132.2 months were included. The radiographic evaluation was performed by assessing peri-prosthetic radiolucent lines around the stem to evaluate loosening, while the clinical evaluation was performed by utilizing elbow range of motion (ROM), Mayo elbow performance score (MEPS), Oxford elbow score (OES) and quick-DASH scores. RESULTS: 13 patients (Group 1) with peri-prosthetic stem lucency were defined as radiographic loosening (50%), while the remaining 13 patients (Group 2) were not detected to have stem lucency. One patient in group 1 also had concomitant pain and underwent removal of the prosthesis, while 12 patients (92.3%) remained pain-free. On the latest follow-up visit, there was no significant difference between the groups regarding ROM, MEPS, OES and quick-DASH scores. CONCLUSIONS: Within ten years following surgery, half of the patients with radial head prostheses were noted to show radiographic signs of loosening which did not have any major negative effect in terms of clinical-functional outcomes and quality of life, except requiring the removal of the implant in one patient. LEVEL OF EVIDENCE: Level III.

Long-term outcomes after arthroscopic transosseous-equivalent repair: clinical and magnetic resonance imaging results of rotator cuff tears at a minimum follow-up of 10 years.

PURPOSE: The objective of this study was to evaluate the long-term functional outcomes and structural integrity of medium to massive rotator cuff tears at 10-12 years of follow-up after arthroscopic transosseous-equivalent (TOE) repair. METHODS: This was a retrospective study of a consecutive series of patients who underwent primary arthroscopic TOE repair of medium- to massive-sized degenerative rotator cuff tears performed by a single surgeon between January 2007 and August 2009. Patients were examined at a minimum follow-up of 10 years, and magnetic resonance imaging (MRI) was performed to assess tendon integrity. The Constant score (CS), American Shoulder and Elbow Surgeons score, and pain level documented using a visual analog scale were compared between intact repairs and recurrent defects. Univariate analysis was performed to identify factors related to recurrent defects. RESULTS: A total of 102 patients met the inclusion criteria, and 79 shoulders in 76 patients (74.5% of eligible patients) with a mean age at surgery of 55 ± 8 years (range, 40-72 years) were available for clinical evaluation at a mean follow-up time of 10.9 years (range, 10-12 years). The mean anteroposterior tear size was 3.1 ± 1.1 cm, and there were 41 medium (52%), 26 large (33%), and 12 massive (15%) tears. MRI was performed in 72 shoulders in 69 patients (91% of available shoulders) and revealed that 13 shoulders had recurrent defects (Sugaya stages 4 and 5). During the follow-up period, 3 patients underwent revision surgery, and the overall recurrent defect rate was 21.3%. A clinically meaningful improvement was observed in all outcome measures at the final follow-up regardless of tendon integrity. Patients with intact repairs showed superior outcomes compared with those with recurrent defects; however, only the overall CS met the threshold for clinical relevance. A significant linear correlation was observed between the Sugaya classification and all outcome scores except the CS pain subscale; however, the strength of correlation was weak. The presence of diabetes (odds ratio [OR], 8.6; 95% confidence interval [CI], 2.25-33.2; P = .002), tear size (OR, 2.08; 95% CI, 1.16-3.46; P = .012), and tear retraction (OR, 4.07; 95% CI, 1.11-14.83; P = .033) were associated with recurrent defects in the univariate analysis. CONCLUSION: Arthroscopic TOE repair of rotator cuff tears provided improved clinical outcomes with a recurrent defect rate of 21.3% at 10-12 years after surgery. Future research focusing on tendon healing is needed as repair integrity on MRI correlates with clinical outcomes.

Combining Neratinib with CDK4/6, mTOR, and MEK Inhibitors in Models of HER2-positive Cancer.

PURPOSE: Neratinib is an irreversible, pan-HER tyrosine kinase inhibitor that is FDA approved for HER2-overexpressing/amplified (HER2+) breast cancer. In this preclinical study, we explored the efficacy of neratinib in combination with inhibitors of downstream signaling in HER2+ cancers in vitro and in vivo. EXPERIMENTAL DESIGN: Cell viability, colony formation assays, and Western blotting were used to determine the effect of neratinib in vitro. In vivo efficacy was assessed with patient-derived xenografts (PDX): two breast, two colorectal, and one esophageal cancer (with HER2 mutations). Four PDXs were derived from patients who received previous HER2-targeted therapy. Proteomics were assessed through reverse phase protein arrays and network-level adaptive responses were assessed through Target Score algorithm. RESULTS: In HER2+ breast cancer cells, neratinib was synergistic with multiple agents, including mTOR inhibitors everolimus and sapanisertib, MEK inhibitor trametinib, CDK4/6 inhibitor palbociclib, and PI3Kα inhibitor alpelisib. We tested efficacy of neratinib with everolimus, trametinib, or palbociclib in five HER2+ PDXs. Neratinib combined with everolimus or trametinib led to a 100% increase in median event-free survival (EFS; tumor doubling time) in 25% (1/4) and 60% (3/5) of models, respectively, while neratinib with palbociclib increased EFS in all five models. Network analysis of adaptive responses demonstrated upregulation of EGFR and HER2 signaling in response to CDK4/6, mTOR, and MEK inhibition, possibly providing an explanation for the observed synergies with neratinib. CONCLUSIONS: Taken together, our results provide strong preclinical evidence for combining neratinib with CDK4/6, mTOR, and MEK inhibitors for the treatment of HER2+ cancer.

The safety and accuracy of the fluoroscopic imaging during proximal femoral fixation: A computerized 3D reappraisal of the joint penetration risk.

BACKGROUND: To assess the success of proximal cephalomedullary nailing operations for treating trochanteric fractures, surgeons utilize 2D fluoroscopy to observe the relative positions of the femoral head and the implant. One distance-based risk parameter, observed from the AP and Lateral projections, is the Tip-Surface Distance(TSD) that dictates how close to the outer cortex should the implant tip be residing to avoid post-surgical complications such as cut-out or joint penetration. In this study, the safety and the accuracy of the orthogonal fluoroscopic imaging were evaluated. METHODS: A femoral head model was created and the risk zone was defined as a hemispherical shell of 5 mm thickness beneath the subchondral cortex, which should not be violated during screw insertion. The remaining hemisphere beneath the risk zone was designated as the safe zone. To assess the effect of head size, each simulation was conducted for 34, 47, and 60 mm diameter(Dfemur) femoral heads. The rate of safe zone violation was calculated for all possible screw endpoints with a TSD of at least 5 mm on fluoroscopic orthogonal views (TSDAP and TSDLat). RESULTS: The minimum risk of joint penetration was achieved when the TSDAP/TSDLat ratio was 1. For Dfemur of 34 mm there was a risk of 91.7% of the safe zone violation when each TSDAP and TSDLat were 5 mm and 0% for 9 mm. For Dfemur of 47 mm, the risk was 92.2% for 5 mm and 0% for 11 mm. For Dfemur of 60 mm, the risk was 92.3% for 5 mm and 0% for 13 mm. Safety maps were constructed for all possible TSD combinations for 34, 47, and 60 mm femoral heads. CONCLUSIONS: Depending solely on the orthogonal fluoroscopic images is not a safe and accurate technique for assessing joint penetration risk during proximal femoral fixation due to the spherical geometry of the femoral head. The screw tip can lie completely outside of the femoral head even when it appears inside, in both orthogonal fluoroscopic views. Evidently, when using TSD, more stringent distance limits should be chosen, contrary to the recommended 5 mm limit. Our safety maps for TSD combinations may be used to check the security of the implantation.