Targeting Endogenous Mechanisms of Brain Resilience for the Treatment and Prevention of Alzheimer's Disease.

Alzheimer's disease is a neurodegenerative disorder which contributes to millions of cases of dementia worldwide. The dominant theoretical models of Alzheimer's disease propose that the brain passively succumbs to disruptions in proteostasis, neuronal dysfunction, inflammatory and other processes, ultimately leading to neurodegeneration and dementia. However, an emerging body of evidence suggests that the adult brain is endowed with endogenous mechanisms of resilience which may enable individuals to remain cognitively intact for years despite underlying pathology. In this brief review, we discuss evidence from basic neuroscience and clinical research which demonstrates the existence of endogenous molecular signaling pathways that can promote resilience to neurodegeneration. The p75 neurotrophin receptor provides one such pathway of resilience due to its role as a fundamental signaling switch which determines neuronal survival or degeneration. We highlight a series of preclinical studies targeting the p75 neurotrophin receptor in mouse models which demonstrate resilience to amyloid. We briefly discuss the design and goals of a recent clinical trial of p75 neurotrophin receptor modulation in patients with mild to moderate Alzheimer's disease. Unique challenges for developing therapeutics and biomarkers which are optimized for targeting and detecting endogenous mechanisms of resilience are also discussed. Altogether, this review motivates further trial work of therapeutics modulating the p75 neurotrophin receptor and other deep biology targets.

Ex vivo biomechanical evaluation of 2.4 mm LCP plate rod constructs versus 2.7 mm LCP applied to the feline tibia.

OBJECTIVE: To compare the stiffness and strength of three plate and rod fixation constructs applied to a feline tibial gap model. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Thirty-three unpaired tibiae obtained from skeletally mature cats. METHODS: The tibiae were randomly divided into three groups. The following implants were then applied to the feline tibiae prior to the creation of a 10 mm diaphyseal gap. Group 1: 2.4 mm locking compression plate (LCP) and 1.0 mm intramedullary pin (IMP). Group 2: 2.4 mm LCP and 1.6 mm IMP. Group 3: 2.7 mm LCP. Subsequently, each specimen was tested for torsion, axial compression, and axial load until construct failure. Student's t-tests were used to compare the torsional and axial stiffness, yield load, and maximum axial force. RESULTS: Group 2 had higher axial stiffness than group 3 (p = .013). Group 1 showed a lower maximum axial force and yield point than groups 2 and 3 (p < .01; p < .05, respectively). There were no among-group differences in torsional stiffness. CONCLUSION: Constructs with a 2.4 mm LCP and 1.6 mm IMP provided the strongest and most rigid constructs in a feline tibia gap model. CLINICAL SIGNIFICANCE: A plate-rod construct combining a 2.4 mm LCP and a 1.6 mm IMP is appropriate for achieving high implant stiffness and resisting maximum axial force in treatment of tibial fractures in cats.

S-1 maintenance therapy in Caucasian patients with metastatic esophagogastric adenocarcinoma-final results of the randomized AIO MATEO phase II trial.

PURPOSE: Platinum-fluoropyrimidine combinations are standard of care for treatment of metastatic esophagogastric adenocarcinoma. The optimal duration of first-line chemotherapy is unknown, however, and maintenance strategies have not yet been established. DESIGN: MATEO is an international randomized phase II trial exploring efficacy and safety of S-1 maintenance therapy in human epidermal growth factor receptor 2 (HER2)-negative advanced esophagogastric adenocarcinoma. After 3 months of first-line platinum-fluoropyrimidine-based induction therapy, patients without progression were randomized in a 2 : 1 allocation to receive S-1 monotherapy (arm A) or to continue combination chemotherapy (arm B). The primary objective was to show non-inferiority of overall survival in the S-1 maintenance group. Progression-free survival, adverse events, and quality of life were secondary endpoints. RESULTS: From 2014 to 2019, 110 and 55 patients were randomized in arm A and arm B, respectively (recruitment closed prematurely). Median overall survival from randomization was 13.4 months for arm A and 11.4 months for arm B [hazard ratio 0.97 (80% confidence interval 0.76-1.23), P = 0.86]. Median progression-free survival from randomization was 4.3 and 6.1 months for arm A versus arm B, respectively [hazard ratio 1.10 (80% confidence interval 0.86-1.39), P = 0.62]. Patients in arm A had numerically fewer treatment-related adverse events (84.9% versus 93.9%) and significantly less peripheral sensory polyneuropathy ≥grade 2 (9.4% versus 36.7%). CONCLUSIONS: S-1 maintenance following platinum-based induction therapy leads to non-inferior survival outcomes compared with the continuation of platinum-based combination. Toxicity patterns favor a fluoropyrimidine maintenance strategy. These data challenge the continued use of platinum combination chemotherapy after response to 3 months induction therapy in patients with advanced human epidermal growth factor receptor 2-negative esophagogastric adenocarcinoma.

Effectiveness and safety of tocilizumab in patients with systemic sclerosis: a propensity score matched controlled observational study of the EUSTAR cohort.

OBJECTIVES: Tocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database. METHODS: Patients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months. RESULTS: Ninety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference -1.0, 95% CI -3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (-6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles. CONCLUSION: Although this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population.

Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study.

BACKGROUND: Lurbinectedin, a selective inhibitor of oncogenic transcription, has shown preclinical antitumor activity against homologous recombination repair-deficient models and preliminary clinical activity in BRCA1/2 breast cancer. PATIENTS AND METHODS: This phase II basket multitumor trial (NCT02454972) evaluated lurbinectedin 3.2 mg/m2 1-h intravenous infusion every 3 weeks in a cohort of 21 patients with pretreated germline BRCA1/2 breast cancer. Patients with any hormone receptor and human epidermal growth factor receptor 2 status were enrolled. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Confirmed partial response (PR) was observed in six patients [ORR = 28.6%; 95% confidence interval (CI) 11.3% to 52.2%] who had received a median of two prior advanced chemotherapy lines. Lurbinectedin was active in both BRCA mutations: four PRs in 11 patients (36.4%) with BRCA2 and two PRs in 10 patients (20.0%) with BRCA1. Median DoR was 8.6 months, median PFS was 4.1 months and median OS was 16.1 months. Stable disease (SD) was observed in 10 patients (47.6%), including 3 with unconfirmed response in a subsequent tumor assessment [ORR unconfirmed = 42.9% (95% CI 21.8% to 66.0%)]. Clinical benefit rate (PR + SD ≥ 4 months) was 76.2% (95% CI 52.8% to 91.8%). No objective response was observed among patients who had received prior poly (ADP-ribose) polymerase inhibitors. The most common treatment-related adverse events (AEs) were nausea (61.9%), fatigue (38.1%) and vomiting (23.8%). These AEs were mostly grade 1/2. The most common grade 3/4 toxicity was neutropenia (42.9%: grade 4, 23.8%: with no febrile neutropenia). CONCLUSIONS: This phase II study met its primary endpoint and showed activity of lurbinectedin in germline BRCA1/2 breast cancer. Lurbinectedin showed a predictable and manageable safety profile. Considering the exploratory aim of this trial as well as previous results in other phase II studies, further development of lurbinectedin in this indication is warranted.

Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study.

BACKGROUND: Pembrolizumab demonstrated durable antitumor activity in 233 patients with previously treated advanced microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) advanced solid tumors in the phase II multicohort KEYNOTE-158 (NCT02628067) study. Herein, we report safety and efficacy outcomes with longer follow-up for more patients with previously treated advanced MSI-H/dMMR noncolorectal cancers who were included in cohort K of the KEYNOTE-158 (NCT02628067) study. PATIENTS AND METHODS: Eligible patients with previously treated advanced noncolorectal MSI-H/dMMR solid tumors, measurable disease as per RECIST v1.1, and Eastern Cooperative Oncology Group performance status of 0 or 1 received pembrolizumab 200 mg Q3W for 35 cycles or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) as per RECIST v1.1 by independent central radiologic review. RESULTS: Three hundred and fifty-one patients with various tumor types were enrolled in KEYNOTE-158 cohort K. The most common tumor types were endometrial (22.5%), gastric (14.5%), and small intestine (7.4%). Median time from first dose to database cut-off (5 October 2020) was 37.5 months (range, 0.2-55.6 months). ORR among 321 patients in the efficacy population (patients who received ≥1 dose of pembrolizumab enrolled ≥6 months before the data cut-off date) was 30.8% [95% confidence interval (CI) 25.8% to 36.2%]. Median duration of response was 47.5 months (range, 2.1+ to 51.1+ months; '+' indicates no progressive disease by the time of last disease assessment). Median progression-free survival was 3.5 months (95% CI 2.3-4.2 months) and median overall survival was 20.1 months (95% CI 14.1-27.1 months). Treatment-related adverse events (AEs) occurred in 227 patients (64.7%). Grade 3-4 treatment-related AEs occurred in 39 patients (11.1%); 3 (0.9%) had grade 5 treatment-related AEs (myocarditis, pneumonia, and Guillain-Barre syndrome, n = 1 each). CONCLUSIONS: Pembrolizumab demonstrated clinically meaningful and durable benefit, with a high ORR of 30.8%, long median duration of response of 47.5 months, and manageable safety across a range of heavily pretreated, advanced MSI-H/dMMR noncolorectal cancers, providing support for use of pembrolizumab in this setting.

Electrochemotherapy as palliative treatment in patients with recurrent and/or metastatic head and neck tumours: features analysis for an early determination of the partial responsive patients.

OBJECTIVE: The aim of this study was to identify features mainly involved in determining the partial response (PR) to the Electrochemotherapy (ECT) in patients with recurrent and/or metastatic head and neck (H&N) tumor; the identified features were also used in a decision chart in order to provide the clinician with a support tool in deciding further therapies. PATIENTS AND METHODS: 131 patients (186 treatment sessions) with recurrent and/or metastatic H&N neoplasm were subjected to ECT. Treatment response was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 two months after the ECT. The grade of bleeding and pain before, at the end and one week after ECT treatment were evaluated. Univariate and multivariate analysis were performed to identify features involved in determining the patient PR. RESULTS: In the context of the univariate analysis, tumor size significantly influenced the response to ECT, with higher PR rate of 58.3%: 28 among 48 patients with lesion size ≤ 3 centimeters (p-value < 0.001 at Chi-square test). Pain and bleeding pre-treatment were positively correlated to PR (p-value < 0.001 at Chi-square test). A difference in the current flowing in the tissue during treatment was also observed in partially responsive patients, where the median current value (6.6 A) was higher than that achieved in patients that did not show PR (3.3 A). In the context of the multivariate analysis, the best performances are achieved with the BART method (accuracy of 84%). The main clinical factors to predict the partial response, among investigated features, that have shown to be considered were the pain value felt before performing the treatment and the median current delivered during the ECT treatment. A decision-making support tool to predict the patient prognosis in terms of response rate could be represented by the decision tree obtained with CART algorithm, where a pain pre-treatment more than 5 and a median delivered current not less than 2.8 A led to the prediction a partial responsive patient with an accuracy of 75%. CONCLUSIONS: The study confirmed that ECT is an interesting antitumoral therapy in advanced chemo- and radio-refractory H&N neoplasms, able to reduce frequent symptoms and to improve the quality of life. Pain pre-treatment and delivered current are the most important variables when predicting the partial response of patients.

Synergies of THESEUS with the large facilities of the 2030s and guest observer opportunities.

The proposed THESEUS mission will vastly expand the capabilities to monitor the high-energy sky. It will specifically exploit large samples of gamma-ray bursts to probe the early universe back to the first generation of stars, and to advance multi-messenger astrophysics by detecting and localizing the counterparts of gravitational waves and cosmic neutrino sources. The combination and coordination of these activities with multi-wavelength, multi-messenger facilities expected to be operating in the 2030s will open new avenues of exploration in many areas of astrophysics, cosmology and fundamental physics, thus adding considerable strength to the overall scientific impact of THESEUS and these facilities. We discuss here a number of these powerful synergies and guest observer opportunities.

Feasibility and relevance of urine culture during stone fragmentation in patients undergoing percutaneous nephrolithotomy and retrograde intrarenal surgery: a prospective study.

PURPOSE: We evaluated if, during lithotripsy, bacteria may be detected in the irrigation fluid of percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS). The concordance between urine culture from stone fragmentation (SFUC), bladder (BUC), renal pelvic (RPUC) and stone (SC) was analyzed. We also assessed the correlation between variables and cultures and their association with systemic inflammatory response syndrome (SIRS) and of a positive SC. METHODS: We included 107 patients who underwent PCNL (n = 53) and RIRS (n = 54) from January 2017 to May 2018. Samples for RPUC were obtained by renal catheterization. Stone fragments and irrigation fluid sample were sent for culture. RESULTS: SFUC was positive in 17 (15.9%), BUC in 22 (20.6%), RPUC in 26 (24.3%) and SC in 30 patients (28%). The concordance between SFUC and SC was the highest among all cultures: 94.1%. SFUC and SC grew identical microorganisms in 15/17 (88.2%) patients. Out of 17 (15.9%) patients with SIRS, 8 (7.5%) had sepsis. SFUC had the highest PPV and specificity to detect positive SC and SIRS. Previous urinary tract infection, a preoperative nephrostomy, stone diameter and composition, staghorn calculi, PCNL, positive BUC, RPUC and SFUC were predictors of infected stone. Variables that indicate complex stones, complex PCNL and an infection of the upper tract were associated with SIRS. CONCLUSION: SFUC is technically feasible, easy to retrieve and to analyze. The spectrum of SFUC potential application in clinical practice is when is not possible to perform a SC, e.g. complete dusting or during micro-PCNL.

Impact of COVID-19 epidemic on maxillofacial surgery in Italy.

Maxillofacial departments in 23 surgical units in Italy have been increasingly involved in facing the COVID-19 emergency. Elective surgeries have been progressively postponed to free up beds and offer human and material resources to those infected. We compiled an inventory of 32 questions to evaluate the impact of the SARS-COV2 epidemic on maxillofacial surgery in 23 selected Italian maxillofacial departments. The questionnaire focused on three different aspects: the variation of the workload, showing both a reduction of the number of team members (-16% among specialists, -11% among residents) due to reallocation or contamination and a consistent reduction of elective activities (the number of outpatient visits cancelled during the first month of the COVID-19 epidemic was about 10 000 all over Italy), while only tumour surgery and trauma surgery has been widely guaranteed; the screening procedures on patients and physicians (22% of maxillofacial units found infected surgeons, which is 4% of all maxillofacial surgeons); and the availability of Personal Protective Equipment, is only considered to be partial in 48% of Maxillofacial departments. This emergency has forced those of us in the Italian health system to change the way we work, but only time will prove if these changes have been effective.

Non-Amyloid Approaches to Disease Modification for Alzheimer's Disease: An EU/US CTAD Task Force Report.

While amyloid-targeting therapies continue to predominate in the Alzheimer's disease (AD) drug development pipeline, there is increasing recognition that to effectively treat the disease it may be necessary to target other mechanisms and pathways as well. In December 2019, The EU/US CTAD Task Force discussed these alternative approaches to disease modification in AD, focusing on tau-targeting therapies, neurotrophin receptor modulation, anti-microbial strategies, and the innate immune response; as well as vascular approaches, aging, and non-pharmacological approaches such as lifestyle intervention strategies, photobiomodulation and neurostimulation. The Task Force proposed a general strategy to accelerate the development of alternative treatment approaches, which would include increased partnerships and collaborations, improved trial designs, and further exploration of combination therapy strategies.

Atypical presentation of acute pancreatitis: a single center case-match analysis of clinical outcomes.

OBJECTIVE: Acute pancreatitis (AP) may present an aspecific clinical picture without abdominal symptoms (atypical AP). We compared clinical outcomes between typical and atypical AP. PATIENTS AND METHODS: Thirty out of 1163 patients (2.6%) presented an atypical AP. Demographic, clinical data, laboratory and radiological findings, management type, length of hospital stay (LOS) and mortality rate were retrospectively reviewed. A case match analysis 2:1 was performed. The final groups comprised 50 typical APs (TAP group) and 25 atypical APs (AAP group). RESULTS: The AAP patients presented fever (36%), syncope (32%) and dyspnea (16%) as the most frequent symptoms. Laboratory values showed similarity between the two groups. We noted a comparable edematous AP rate in both groups (p=0.36). Ten (20%) TAP and 3 (12%) AAP patients needed ERCP, respectively (p=0.38). Cholecystectomy was similarly performed in both cohorts (p=0.81). One TAP patient underwent a percutaneous drainage and subsequent surgical necrosectomy compared to none in the AAP cohort (p=0.47). LOS and mortality rate were comparable (p=0.76 and 0.3, respectively). CONCLUSIONS: Similar outcomes have been reached in the two groups. Routine evaluation of the serum amylase values fundamentally contributed to early diagnosis and appropriate treatment.

Giant mature teratoma in thymic tissue removed with uniportal vats approach.

INTRODUCTION: Teratomas are tumours composed by different tissues derived from one or more of the three primitive germ cell layers. The frequency of mediastinal teratomas ranged from 1 to 5 %, in most cases with localization in the anterior/superior mediastinum. PRESENTATION OF CASE: We report a case report of a 29 years old male who presented an occasional and asymptomatic mediastinal mass. Computer Tomography (CT) scan showed a 6.8 × 4.5 cm mass in the anterior mediastino, located below the left brachio-cephalic vein, next to aortic arch and left pulmonary artery. Complete excision of the mass "en block" with anterior mediastinal adipose tissue was achieved, using uniportal VATS approach. The postoperative course was regular, without air leak or other pulmonary complication. DISCUSSION: VATS technique is minimally invasive and, moreover, it is characterized by a shorter recovery period, a minor blood loss and a shorter hospital stay. VATS has been advocated since 2010 for pulmonary resections, but today it is also performed for mediastinal intervention and a series of reports have demonstrated that it is feasible and safe. CONCLUSION: The report aims at pointing out the possibility of undergoing this kind of surgery not only in case of pulmonary mass (on which the previous literature has focused) but also when mediastinum lesions occur, as in our case.

Differences in clinical manifestations and increased severity of systemic lupus erythematosus between two groups of Hispanics: European Caucasians versus Latin American mestizos (data from the RELESSER registry).

BACKGROUND: Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations. OBJECTIVES: This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences. METHODS: This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out. RESULTS: A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038-2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30-1.66)). CONCLUSION: SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.

Thyroid profile during the alternative Sunitinib dosing 2/1 schedule in metastatic renal cell carcinoma.

PURPOSE: Hypothyroidism is a common side effect of Sunitinib (SUN) treatment in metastatic renal cell carcinoma (mRCC) patients. We aimed to evaluate thyroid profile during the alternative 2/1 SUN treatment schedule and to assess the predictive value of hypothyroidism in terms of survival. METHODS: We performed a prospective observational study enrolling 42 consecutive mRCC patients starting first-line alternative SUN dosing 2/1 schedule. Thyroid function was assessed at baseline and during the first three SUN cycles (1 cycle = 6 weeks = 2 ON/1 OFF + 2 ON/1 OFF), and then after 6 and 12 months. Thyroid ultrasound was performed at baseline and after 3, 6, and 12 months. RESULTS: Subclinical hypothyroidism developed in 24% of patients during the first cycle; in other 24% in the second cycle and in 14% in the third cycle. The highest TSH values were reached during the second cycle, ON phase (6.58 ± 5.74 µI U/l). We observed a reduction in thyroid size, in echogenicity and in parenchymal perfusion in all patients. Progression-free survival (PFS) tended to be longer in patients with TSH ≥ 5 µI U/ml during the second cycle (p = 0.069). TSH level was an independent risk factor for PFS in men (p = 0.009) but not in women (p = 0.285). CONCLUSIONS: This is the first study investigating functional and morphological effects on thyroid during the alternative 2/1 SUN schedule in mRCC patients. We detected an early onset of subclinical hypothyroidism, observing the association between TSH ≥ 5 µI U/ml and: (i) longer PFS in men; (ii) progressive decrease of thyroid size in absence of significant changes in autoimmune thyroid profile.

[Treatment of a hip and patella luxation in a toy dog]. / Behandlung einer Hüftgelenks- und Kniescheiben-Luxation bei einer Zwerghunderasse.

INTRODUCTION: The present case report describes the surgical treatment of a traumatic craniodorsal luxation of the hip and a concomitant medial congenital luxation of the patella (3rd grade) in an 11-year-old Yorkshire Terrier. First the hip luxation was corrected with a cemented hip prosthesis. The femoral stem was inserted in slight anteversion (15°) with respect to the preoperative condition (5°), this contributed contrasting the medial traction of the femoral quadriceps on the patella, improving patellar luxation from 3rd to 2nd grade. However, the persistent patellar luxation and intermittent lameness reduced limb function and made a second intervention necessary. Four weeks after prosthetic surgery, a femoral trocleoplasty and lateral transposition of the tibial crest were performed to definitively re-establish a correct replacement of the patella in the femoral trochlea. No perioperative complications were found. At the final examination the patient did not show any lameness or pain that could be evoked when manipulating the surgically corrected limb. The surgical treatment allowed a restoration of the hip function and the alignment of the extensor mechanism of the femoral quadriceps and ensured a complete return to normal motor activities.

INTRODUCTION: Nous décrivons le traitement chirurgical d'une luxation traumatique cranio-dorsale de la hanche et d'une luxation patellaire de degré 3 concomitante chez un chien Yorkshire Terrier âgé de 11 ans. La luxation de la hanche a d'abord été traitée avec une prothèse totale cimentée. L'insertion de la tige fémorale en légère antéversion (15°) par rapport à l'état préopératoire (5°) contrecarrait la traction médiale des muscles quadriceps sur la rotule et réduisait la luxation patellaire du degré 3 au degré 2. Cependant la présence d'une boiterie intermittente due à la luxation patellaire de degré 2 persistante a réduit la fonction du membre et a rendu nécessaire une seconde intervention chirurgicale. Quatre semaines après le remplacement total de la hanche, une trochléoplastie fémorale et une transposition latérale de la crête tibiale ont été réalisées afin d'établir définitivement un alignement correct de la rotule dans la trochlée fémorale. Aucune complication périopératoire n'a été rencontrée. Lors de dernier contrôle, le patient ne présentait pas de boiterie ni de douleur lors de la manipulation du membre opéré Le traitement chirurgical a permis de rétablir la fonction de la hanche et d'aligner correctement le mécanisme extenseur des muscles quadriceps, tout en garantissant un retour complet du patient à une activité physique normale.

Three-dimensional computer-assisted corrective osteotomy with a patient-specific surgical guide for an antebrachial limb deformity in two dogs.

INTRODUCTION: We describe patient-specific surgical guide prototyping and surgical treatment of a complex antebrachial deformity in two skeletally mature dogs presented with chronic lameness. Computer-assisted surgery was elected to increase accuracy in the correction of the complex deformity. Radiographs and computed tomography (CT) scans revealed a biplane deformity with valgus, procurvatum and external torsion of the right radius in both cases. The pre-surgical planning started from the quantification of the angular deformity, followed by computer simulated correction and to end up with a rehearsal surgery on 3D printed bone models. During the surgery, the custom-made osteotomy guides closely fitted the bone, allowing for a precise corrective osteotomy, that was stabilized with two locking plates. Postoperative radiographs showed the successful correction of the deformity. Eight and 12 weeks postoperative follow up examinations showed improved lameness, weight-bearing and progression of bone healing in both dogs. Patient-specific surgical guides allowed for a satisfactory correction of the antebrachial deformity. Additional benefits of using customized surgical devices include standardization and reduced surgical time.

INTRODUCTION: Nous décrivons le prototypage d'une procédure chirurgicale spécifique au patient et le traitement chirurgical d'une déformation antébrachiale complexe chez deux chiens ayant atteint leur maturité squelettique et présentant une boiterie chronique. La chirurgie assistée par ordinateur a été choisie pour accroître la précision de la correction de la déformation complexe. Les radiographies et la tomodensitométrie (TDM) ont révélé une déformation dans deux plans avec valgus, procurvatum et torsion externe du radius droit dans les deux cas. La planification préopératoire a commencé par la quantification de la déformation angulaire, suivie par une correction simulée sur ordinateur et a abouti à une opération de répétition sur des modèles d'os imprimés en 3D. Pendant l'intervention, des guides d'ostéotomie sur mesure ont ajusté l'os de manière exacte, permettant ainsi une ostéotomie correctrice précise, stabilisée avec deux plaques de verrouillage. Les radiographies postopératoires ont montré la réussite de le correction de la déformation. Les examens de suivi postopératoires effectués à huit et douze semaines ont montré une amélioration de la boiterie et de la mise en charge ainsi que la progression de la cicatrisation des os chez les deux chiens. Les guides chirurgicaux spécifiques au patient ont ­permis une correction satisfaisante de la déformation antébrachiale. L'utilisation de matériel chirurgical personnalisé comporte d'autres avantages, tels que la standardisation et la réduction du temps de l'intervention chirurgicale.