Comparative analysis of the quality of life regarding patients who underwent hip replacement in public versus private hospitals in Hungary.

The study aimed to investigate the impact of hip replacement surgery on the quality of life and to compare the outcomes by sociodemographic and surgical data in Hungarian public and private hospitals. Patients were selected at the Department of Orthopaedics (Clinical Centre, University of Pécs) and at the Da Vinci Private Clinic in Pécs. Patients completed the SF-36 and Oxford Hip Score (OHS) questionnaires before the surgery, 6 weeks and 3 months later. We also evaluated socio-demographic data, disease and surgical conditions. The research involved 128 patients, 60 patients in public, 68 patients in private hospital. Despite the different sociodemographic characteristics and surgical outcomes of public and private healthcare patients, both groups had significantly improved the quality of life 3 months after hip replacement surgery measured by OHS and SF-36 physical health scores (p < 0.001). In the mental health score, only the patients of the private health sector showed a significant improvement (p < 0.001). The extent of improvement did not differ between the two healthcare sectors according to the OHS questionnaire (p = 0.985). While the SF-36 physical health score showed a higher improvement for public patients (p = 0.027), the mental health score showed a higher improvement for private patients (p = 0.015).

Effectiveness of Postoperative Single-shot and Continuous Transverse Abdominis Plane Block Compared to Conventional Analgesia in Hand-assisted Laparoscopic Live-donor Nephrectomy.

Background: Few studies have evaluated the efficacy of transverse abdominis plane (TAP) block in patients undergoing hand-assisted laparoscopic live-donor nephrectomy (HALN). We aimed to evaluate the analgesic effectiveness of TAP block as part of a multimodal pain management regimen in patients undergoing HALN. Methods: We retrospectively reviewed the medical records of living kidney donors at our center between June 2016 and February 2020. HALNs were performed via a transperitoneal approach through a suprapubic incision. Additional laparoscopic ports were used in the upper midabdomen. In consenting donors, TAP block was performed postoperatively under ultrasound guidance with either a single-shot or continuous infusion of long-acting local anesthetic (0.2%-0.5% ropivacaine). All the patients received postoperative around-the-clock ketorolac and acetaminophen. Results: Overall, 72 donors received the block (block group, 38 single-shot, 34 continuous), whereas 86 donors did not receive the block (control group). Baseline characteristics were comparable between the groups except for body weight (control: 71.8 ±â€…13.3 versus block: 77.8 ±â€…17.3 kg; P = 0.01) and intraoperative opioid dose (32.1 ±â€…9.6 versus 26.6 ±â€…10.7 morphine milligram equivalents; P < 0.001). After adjusting for baseline differences, postoperative opioid requirements were similar between the groups. When the baseline pain scale was adjusted for, there was no difference in the overall pain scale scores between the groups (P = 0.242). Subgroup analyses comparing single-shot or continuous TAP versus control did not show any differences. Conclusions: With the caveat of the retrospective nature of the study, the adjunctive effect of TAP block after transabdominal HALN was limited when other multimodal analgesia was used.

Prediction of High-Risk Donors for Kidney Discard and Nonrecovery Using Structured Donor Characteristics and Unstructured Donor Narratives.

Importance: Despite the unmet need, many deceased-donor kidneys are discarded or not recovered. Inefficient allocation and prolonged ischemia time are contributing factors, and early detection of high-risk donors may reduce organ loss. Objective: To evaluate the feasibility of machine learning (ML) and natural language processing (NLP) classification of donors with kidneys that are used vs not used for organ transplant. Design, Setting, and Participants: This retrospective cohort study used donor information (structured donor characteristics and unstructured donor narratives) from the United Network for Organ Sharing (UNOS). All donor offers to a single transplant center between January 2015 and December 2020 were used to train and validate ML models to predict donors who had at least 1 kidney transplanted (at our center or another center). The donor data from 2021 were used to test each model. Exposures: Donor information was provided by UNOS to the transplant centers with potential transplant candidates. Each center evaluated the donor and decided within an allotted time whether to accept the kidney for organ transplant. Main Outcomes and Measures: Outcome metrics of the test cohort included area under the receiver operating characteristic curve (AUROC), F1 score, accuracy, precision, and recall of each ML classifier. Feature importance and Shapley additive explanation (SHAP) summaries were assessed for model explainability. Results: The training/validation cohort included 9555 donors (median [IQR] age, 50 [36-58] years; 5571 male [58.3%]), and the test cohort included 2481 donors (median [IQR] age, 52 [40-59] years; 1496 male [60.3%]). Only 20% to 30% of potential donors had at least 1 kidney transplanted. The ML model with a single variable (Kidney Donor Profile Index) showed an AUROC of 0.69, F1 score of 0.42, and accuracy of 0.64. Multivariable ML models based on basic a priori structured donor data showed similar metrics (logistic regression: AUROC = 0.70; F1 score = 0.42; accuracy = 0.62; random forest classifier: AUROC = 0.69; F1 score = 0.42; accuracy = 0.64). The classic NLP model (bag-of-words model) showed its best metrics (AUROC = 0.60; F1 score = 0.35; accuracy = 0.59) by the logistic regression classifier. The advanced Bidirectional Encoder Representations From Transformers model showed comparable metrics (AUROC = 0.62; F1 score = 0.39; accuracy = 0.69) only after appending basic donor information. Feature importance and SHAP detected the variables (and words) that affected the models most. Conclusions and Relevance: Results of this cohort study suggest that models using ML can be applied to predict donors with high-risk kidneys not used for organ transplant, but the models still need further elaboration. The use of unstructured data is likely to expand the possibilities; further exploration of new approaches will be necessary to develop models with better predictive metrics.

Allometrically scaling tissue forces drive pathological foreign-body responses to implants via Rac2-activated myeloid cells.

Small animals do not replicate the severity of the human foreign-body response (FBR) to implants. Here we show that the FBR can be driven by forces generated at the implant surface that, owing to allometric scaling, increase exponentially with body size. We found that the human FBR is mediated by immune-cell-specific RAC2 mechanotransduction signalling, independently of the chemistry and mechanical properties of the implant, and that a pathological FBR that is human-like at the molecular, cellular and tissue levels can be induced in mice via the application of human-tissue-scale forces through a vibrating silicone implant. FBRs to such elevated extrinsic forces in the mice were also mediated by the activation of Rac2 signalling in a subpopulation of mechanoresponsive myeloid cells, which could be substantially reduced via the pharmacological or genetic inhibition of Rac2. Our findings provide an explanation for the stark differences in FBRs observed in small animals and humans, and have implications for the design and safety of implantable devices.

Long-term Survival of Grafts From Small and Very Small Pediatric Donors in Women vs Men With End-stage Kidney Disease.

This cohort study compares graft survival of kidneys from small and very small pediatric donors in women vs men with end-stage kidney disease.

Neck-shaft angle measurement in children: accuracy of the conventional radiography-based (2D) methods compared to 3D reconstructions.

Aim of this study was to examine the accuracy of widely used conventional radiography-based (2D) neck-shaft angle measurements compared to 3D reconstruction. In our retrospective study, EOS 2D/3D images of 156 patients (312 limbs) were selected from our database (4-16 years old: 6 girls and 6 boys/year), where no pathology was revealed. Using the 2D modality of the EOS method neck-shaft angle was measured using the "biggest diameter" and "circle fitting" techniques to define the femoral neck axis and 1/3, 1/2 and full femur to determine the femoral shaft axis. EOS 3D reconstructions of same images were also performed and a comparison of 2D and 3D results was made. We did not find any significant difference between accuracy of the four examined 2D methods, although the deviation between 2 and 3D results was considerable (average difference: 5.11-5.58°, p < 0,001). In 31% of the cases, difference was more than 10°. Only femoral torsion showed significant influence on the difference (correlation coefficient: 0.380, p < 0.001). We did not find a clinically significant difference between the examined 2D methods, although their accuracy was highly questionable compared to 3D results. We suggest using any 3D imaging method for surgical planning and in uncertain cases.

Effect of single end-range and not end-range Maitland mobilization on pressure pain threshold and functional measures in knee osteoarthritis: randomised, controlled clinical trial.

BACKGROUND: Hyperalgesia is attributed to peripheral and central sensitization in knee osteoarthritis (OA). Pressure pain threshold (PPT) is a relevant method for evaluating pain sensitivity in knee OA. The effect of end-range and not end-range Maitland mobilization for certain time-period on pain sensitivity has not been investigated in knee OA. AIM: The aim of this study was to investigate the effect of end-range and not end-range Maitland mobilization compared to sham manual therapy technique on PPT and functional measures. DESIGN: Randomised, controlled clinical trial. SETTING: Outpatient setting. POPULATION: Sixty-six patients with mild-to-severe knee OA. METHODS: Twenty-one patients (N.=21) received end-range Maitland mobilization (EMGr), twenty patients (N.=20) received not end-range Maitland mobilization (nEMGr) and twenty-two patients (N.=22) received sham manual therapy technique (CG). All interventions were performed once. Evaluation was conducted pre-, postintervention and on the following consecutive second days within a 6-day period. Outcomes were local and distant PPT, Timed Up and Go Test (TUG) and strength of passive resistance of knee at onset of pain. RESULTS: Local and distant PPT increased, TUG time and strength of passive resistance decreased immediately, local and distant PPT remained decreased in 6-day and 4-day period, TUG time remained decreased in 6-day period in EMGr (all changes P≤0.017). Local PPT increased immediately compared to baseline in nEMGr. In between group comparison, increase of local, distant PPT and strength of passive resistance endures on 2nd day, 4th day and postintervention, respectively, in EMGr compared to CG. EMGr compared to nEMGr presented significant difference on 6th day and 4th day in local and distant PPT, respectively (all changes P≤0.021). NEMGr presented no significant difference compared to CG on either follow-up. CONCLUSIONS: Single end-range Maitland mobilization is effective immediately and in 4-day period on pain sensitization and immediately on physical function compared to not end-range Maitland mobilization and sham manual therapy technique in knee OA. CLINICAL REHABILITATION IMPACT: Based on the present results, applying end-range Maitland mobilization is suggested on every second day to maintain alleviation of pain sensitization and increasing passive knee joint mobility effectively in knee OA.

Investigation of the short-term quality of life and socio-demographic factors of patients undergoing total hip arthroplasty / Csípoízületi protézismutéten átesett betegek szociodemográfiai jellemzoinek és rövid távú életminoségének vizsgálata

Introduction: Among the health needs related to an aging society, the increase in the number of hip replacement surgeries stands out. Objective: The study aimed to examine the socio-demographic data of patients operated in the private and state health care with total hip arthroplasty in different approaches, and to compare their quality of life before and after surgery. Data and methods: Patients were selected by simple convenience sampling technique at the Department of Orthopedics, Clinical Centre of the University of Pecs and at the Da Vinci Private Clinic in Pecs. Patients completed a complex questionnaire before the surgery and 6 weeks later. We evaluated socio-demographic data, disease and surgical conditions. Two international questionnaires were also completed (SF-36, Oxford Hip Score). Results: The research involved 164 persons, 75 persons of the state care, 89 persons of the private care. The proportion of villagers was significantly higher in the state care (p = 0.014), while mainly metropolitans were found in the private care. The proportion of primary (p < 0.001) and secondary education (p = 0.042) was significantly higher for state care patients, while higher education was prevalent among patients treated in the private sector (p < 0.001). In the state care the proportion of pensioners (p = 0.005), in the private care the proportion of intellectual workers and contractors was significantly higher (p < 0.001). Both groups' quality of life showed significant improvement (p < 0.001). Conclusion: Patients in the two groups significantly differed in socio-demographic characteristics, but both showed significant improvements in the quality of life 6 weeks after surgery.

Alternative methods for skeletal maturity estimation with the EOS scanner-Experience from 934 patients.

BACKGROUND: Hand-wrist bone age assessment methods are not possible on typical EOS 2D/3D images without body position modifications that may affect spinal position. We aimed to identify and assess lesser known bone age assessment alternatives that may be applied retrospectively and without the need for extra imaging. MATERIALS AND METHODS: After review of 2857 articles, nine bone age methods were selected and applied retrospectively in pilot study (thirteen individuals), followed by evaluation of EOS images of 934 4-24-year-olds. Difficulty of assessment and time taken were recorded, and reliability calculated. RESULTS: Five methods proved promising after pilot study. Risser 'plus' could be applied with no difficulty in 89.5% of scans (836/934) followed by the Oxford hip method (78.6%, 734/934), cervical (79.0%, 738/934), calcaneus (70.8%, 669/934) and the knee (68.2%, 667/934). Calcaneus and cervical methods proved to be fastest at 17.7s (95% confidence interval, 16.0s to 19.38s & 26.5s (95% CI, 22.16s to 30.75s), respectively, with Oxford hip the slowest at 82.0 s (95% CI, 76.12 to 87.88s). Difficulties included: regions lying outside of the image-assessment was difficult or impossible in upper cervical vertebrae (46/934 images 4.9%) and calcaneus methods (144/934 images, 15.4%); position: lower step length was associated with difficult lateral knee assessment & head/hand position with cervical evaluation; and resolution: in the higher stages of the hip, calcaneal and knee methods. CONCLUSIONS: Hip, iliac crest and cervical regions can be assessed on the majority of EOS scans and may be useful for retrospective application. Calcaneus evaluation is a simple and rapidly applicable method that may be appropriate if consideration is given to include full imaging of the foot.

End-range Maitland mobilization decreasing pain sensitivity in knee osteoarthritis: randomized, controlled clinical trial.

BACKGROUND: Pressure pain threshold (PPT) is a widely applied method for measuring the magnitude of increased peripheral and central pain sensitivity causing hyperalgesia in knee osteoarthritis (OA). Although manual therapy techniques effects positively PPT, the effect of end-range Maitland mobilization has not been evaluated in knee OA. AIM: The aim of this study was to investigate the effect of end-range Maitland mobilization compared to sham manual therapy technique on PPT and function-related measures. DESIGN: The design of the study was of a randomized, controlled clinical trial. SETTING: Outpatient setting. POPULATION: Forty women with moderate-to-severe knee OA. METHODS: Twenty patients (N.=20) were randomly assigned to Maitland group (MG) and twenty patients (N.=20) to control group (CG). Patients in MG received single end-range Maitland mobilization while patients in CG received sham manual therapy technique. Assessment was performed at baseline, 30 minutes and after 1-week period. Outcome measures were PPT locally at knee and distant at ipsilateral extensor carpi radialis longus muscle, general pain during the previous week using the Visual Analogue Scale (VAS), Timed Up and Go Test (TUG) time associated with pain measured with Numerating Pain Rating Scale (NPRS) and strength of passive resistance of knee at onset of pain. RESULTS: Despite all outcome measures improved significantly postintervention, no changes were detected after 1-week period compared to postintervention in MG. No change of outcome measures was found also postintervention and after 1-week period compared to postintervention in CG. All postintervention results showed significant improvement in between-group comparison in favor of MG. However, after 1-week period, only strength of passive resistance revealed significant difference in between-group comparison in favor of MG (P<0.001). CONCLUSIONS: Although end-range Maitland mobilization has an immediate effect on decreasing peripheral and central pain sensitivity and improving function-related measures in knee OA, these changes may not cause clinically relevant effect based on data measured after 1-week period. CLINICAL REHABILITATION IMPACT: Investigating the time-course of end-range Maitland mobilization for determining the optimal treatment frequency during rehabilitation is suggested in knee OA.

Maximal Axial Vertebral Rotation in Adolescent Idiopathic Scoliosis: Is the Apical Vertebra the Most Rotated?

STUDY DESIGN: Retrospective cross-sectional study. OBJECTIVES: It is generally believed that the apical vertebra has the largest axial rotation in adolescent idiopathic scoliosis. We investigated the relationship between apical axial vertebral rotation (apicalAVR) and maximal axial vertebral rotation (maxAVR) in both major and minor curves using biplanar stereo-imaging. METHODS: EOS 2D/3D biplanar radiograph images were collected from 332 patients with adolescent idiopathic scoliosis (Cobb angle range 10°-122°, mean age 14.7 years). Based on the X-ray images, with the help of 3D full spine reconstructions Cobb angle, curvature level, apicalAVR and maxAVR were determined. These parameters were also determined for minor curves in Lenke 2, 3, 4, 6 type patients. Maximal thoracic rotation and maximal thoracolumbar/lumbar rotation were calculated. Statistical analysis was performed with descriptive statistics, Shapiro-Wilk test, and Wilcoxon signed-rank test. RESULTS: The apical vertebrae were the most rotated vertebra in only 40.4% of the major curves, and 31.7% in minor curves. MaxAVR significantly exceeded apicalAVR values in the major curves (P < .001) as well as in minor curves (P < .001). The 2 parameters differed significantly in each severity group and Lenke type. CONCLUSIONS: The apical vertebrae were not the most rotated vertebra in more than half of cases investigated indicating that apicalAVR and maxAVR should be considered as 2 distinct parameters, of which maxAVR fully describes the axial dimension of scoliosis. Furthermore, the substitution of maxAVR for the apicalAVR should be especially avoided in double and triple curves, as the apical vertebra was even less commonly the most rotated in minor curves.

Selective Microvascular Tissue Transfection Using Minicircle DNA for Systemic Delivery of Human Coagulation Factor IX in a Rat Model Using a Therapeutic Flap.

BACKGROUND: Gene therapy is a promising treatment for protein deficiency disorders such as hemophilia B. However, low tissue selectivity and efficacy are limitations of systemic vector delivery. The authors hypothesized that selective transfection of rat superficial inferior epigastric artery flaps could provide systemic delivery of coagulation factor IX, preventing the need for systemic vector administration. METHODS: Minicircle DNA containing green fluorescent protein, firefly luciferase, and human coagulation factor IX was created. Vector constructs were validated by transfecting adipose-derived stromal cells isolated from Wistar rat superficial inferior epigastric artery flaps and evaluating transgene expression by fluorescence microscopy, bioluminescence, and enzyme-linked immunosorbent assay. Minicircle DNA luciferase (10 and 30 µg) was injected into murine (wild-type, C57/BL/6) inguinal fat pads (n = 3) and followed by in vivo bioluminescence imaging for 60 days. Wistar rat superficial inferior epigastric artery flaps were transfected with minicircle DNA human coagulation factor IX (n = 9) with plasma and tissue transgene expression measured by enzyme-linked immunosorbent assay at 2 and 4 weeks. RESULTS: Transfected adipose-derived stromal cells expressed green fluorescent protein for 30 days, luciferase for 43 days, and human coagulation factor IX (21.9 ± 1.2 ng/ml) for 28 days in vitro. In vivo murine studies demonstrated dose-dependence between minicircle DNA delivery and protein expression. Ex vivo rat superficial inferior epigastric artery flap transfection with minicircle DNA human coagulation factor IX showed systemic transgene expression at 2 (266.6 ± 23.4 ng/ml) and 4 weeks (290.1 ± 17.1 ng/ml) compared to control tissue (p < 0.0001). CONCLUSIONS: Rat superficial inferior epigastric artery flap transfection using minicircle DNA human coagulation factor IX resulted in systemic transgene detection, suggesting that selective flap or angiosome-based tissue transfection may be explored as a treatment for systemic protein deficiency disorders such as hemophilia B.

Effectivity of near-peer teaching in training of basic surgical skills - a randomized controlled trial.

BACKGROUND: Near-peer teaching (NPT) is a special way of teaching where the tutor is one or more academic years ahead of the person being tutored. The literature agrees on the benefits of the method, but there are only a few publications examining its effectiveness using objective methods. The aim of our study was to examine the effectiveness of NPT in the training of basic surgical skills. METHODS: We included 60 volunteer students who participated in a 20 × 45 min long surgical skills course. Based on the results of a pre-course test, we randomly divided the students into six equal groups. All groups completed the same curriculum, with three groups being assisted by a NPT tutor. After the course, they completed the same test as at the beginning. The exams were recorded on anonymized videos and were blindly evaluated. The students' satisfaction was monitored using a self-administered online anonymous questionnaire. Statistical analysis was performed using the Mann-Whitney and Wilcoxon tests. RESULTS: Overall, student performance improved with completion of the course (from 119.86 to 153.55 points, p <  0.01). In groups where a NPT tutor assisted, students achieved a significantly better score (37.20 vs. 30.18 points improvement, p = 0.036). The difference was prominent in surgical knotting tasks (14.73 vs. 9.30 points improvement, p <  0.01). In cases of suturing (15.90 vs. 15.46 points) and laparoscopy (7.00 vs. 4.98 points), the presence of the NPT tutor did not significantly affect development. Based on student feedback, although students positively assessed the presence of NPT, it did not significantly improve students' overall satisfaction since it was already 4,82 on a scale of 5 in the control group. CONCLUSIONS: Overall, involving a NPT tutor had a positive impact on student development. An outstanding difference was observed in connection with knotting techniques.

Operative Technique of Donor Organ Procurement for En Bloc Heart-liver Transplantation.

Combined heart-liver transplant is an emerging option for patients with indications for heart transplantation and otherwise prohibitive hepatic dysfunction. Heart-liver transplantation is particularly relevant for patients with single ventricle physiology who often develop Fontan-associated liver disease and fibrosis. Although only performed at a limited number of centers, several approaches to combined heart-liver transplantation have been described. The en bloc technique offers several potential advantages over the traditional sequential technique. Specifically, en bloc heart-liver transplantation may allow improved hemodynamics, decreased bleeding, reduced liver allograft ischemic time, and may result in reduced rates of graft dysfunction. Here we describe our center's en bloc heart-liver procurement technique in detail, with the aim of allowing broader use and standardization of this technique.

Femoral neck-shaft angle and bone age in 4- to 24-year-olds based on 1005 EOS three-dimensional reconstructions.

The aim of the study was to assess the correlation between femoral neck-shaft angles (NSAs) and skeletal maturity in EOS reconstructions from a large population of children. Full-body three-dimensional (3D) reconstructions were generated from 1005 children and young adults (4-24 years old; 449 male, 556 female) using the EOS three-dimensional/3D scanner, with images taken during routine clinical practice. The true NSAs were measured and assessed for correlation with individuals' chronological age and bone age, based on cervical vertebral morphology. Statistical analysis was performed using Spearman correlation, independent t-test and multiple linear regression. NSAs of older and younger individuals within each bone age group and chronological age were further assessed by t-test. NSA values fell from mean 131.89° ± 6.07° at 4 years old to 128.85° ± 4.46° at the age of 16, with only minor decreases thereafter. Significantly higher NSAs (3.16° and 4.45°, respectively) were found in those with a bone age advanced or delayed by more two or more stages compared to their peers of the same chronological age (P < 0.001; P < 0.001). Similarly, within most bone age stages, individuals of advanced or delayed chronological age exhibited elevated values (mean difference ranged from 2.9° to 8.9°, P < 0.05). Incorporation of bone age assessment into proximal femoral evaluation allowed identification of 'fast maturing' and 'slow maturing' sub-categories in developing children, with different expected NSAs. The earlier ossification seen in faster-maturing individuals may lead to the NSA becoming fixed in a more immature valgus conformation.

[Long-term follow-up of achillotenotomy in patients with cerebral palsy]. / Achillotenotomiák hosszú távú eredményei spasticus cerebralis paresisben szenvedo betegekben.

Introduction: The surgical solution of equinus deformity is one of the most important factors in the treatment of patients with cerebral palsy. We perform open Z achillotenotomy and percutaneus triple hemisection routinely in our department. Aim: The goal of our work was to analyze the long-term results of achillotenotomies in patients with cerebral palsy, to look for predisposing factors of major complications, and to compare the results of the performed operative methods. Method: Between 1990 and 2006, we performed 347 surgical Achilles tendon lengthenings. In 261 cases, the operations were performed percutaneusly, and in 86 cases we performed open Z achillotenotomy. The average follow-up time was 15 years. The long-term outcomes were analyzed based on the age at surgery, the topographic appearance and the severity of cerebral palsy. Analysis regarding functional outcome was based on the widely known Physician Rating Scale system. Results: Due to recurrent equinus deformity, re-achillotenotomy was performed in 74 cases (21.3%), and in 14 cases (4%) the re-achillotenotomy needed to be performed a second time. We encountered overcorrection and calcaneus deformity in 12 cases (3.5%). Recurrence rate was higher in patients operated at a younger age (<7 years) and in patients with a more severe cerebral palsy (GMFCS II-III, ~26%). Recurrence showed accumulation in patients 9-14 years old. Conclusion: The major complication we encountered was recurrence of the equinus deformity. The majority of relapses occured in patients who were operated at a younger age and suffered from a more severe form of cerebral palsy. We observed that recurrence showed an association with growth and accumulated in aldolescence. Orv Hetil. 2020; 161(8): 306-312.

Therapeutic Breast Reconstruction Using Gene Therapy-Delivered IFNγ Immunotherapy.

After mastectomy, breast reconstruction is increasingly performed using autologous tissue with the aim of improving quality of life. During this procedure, autologous tissue is excised, relocated, and reattached using microvascular anastomoses at the site of the extirpated breast. The period during which the tissue is ex vivo may allow genetic modification without any systemic exposure to the vector. Could such access permit delivery of therapeutic agents using the tissue flap as a vehicle? Such delivery may be more targeted and oncologically efficient than systemic therapy, and avoid systemic complications. The cytokine IFNγ has antitumor effects, and systemic toxicity could be circumvented by localized delivery of the IFNγ gene via gene therapy to autologous tissue used for breast reconstruction, which then releases IFNγ and exerts antitumor effects. In a rat model of loco-regional recurrence (LRR) with MADB-106-Luc and MAD-MB-231-Luc breast cancer cells, autologous tissue was transduced ex vivo with an adeno-associated viral vector encoding IFNγ. The "Therapeutic Reconstruction" released IFNγ at the LRR site and eliminated cancer cells, significantly decreased tumor burden, and increased survival compared with sham reconstruction (P <0.05). Mechanistically, localized IFNγ immunotherapy stimulated M1 macrophages to target cancer cells within the regional confines of the modified tumor environment. This concept of "Therapeutic Breast Reconstruction" using ex vivo gene therapy of autologous tissue offers a new application for immunotherapy in breast cancer with a dual therapeutic effect of both reconstructing the ablative defect and delivering local adjuvant immunotherapy.

The Interplay of Mechanical Stress, Strain, and Stiffness at the Keloid Periphery Correlates with Increased Caveolin-1/ROCK Signaling and Scar Progression.

BACKGROUND: Fibroproliferative disorders result in excessive scar formation, are associated with high morbidity, and cost billions of dollars every year. Of these, keloid disease presents a particularly challenging clinical problem because the cutaneous scars progress beyond the original site of injury. Altered mechanotransduction has been implicated in keloid development, but the mechanisms governing scar progression into the surrounding tissue remain unknown. The role of mechanotransduction in keloids is further complicated by the differential mechanical properties of keloids and the surrounding skin. METHODS: The authors used human mechanical testing, finite element modeling, and immunohistologic analyses of human specimens to clarify the complex interplay of mechanical stress, strain, and stiffness in keloid scar progression. RESULTS: Changes in human position (i.e., standing, sitting, and supine) are correlated to dynamic changes in local stress/strain distribution, particularly in regions with a predilection for keloids. Keloids are composed of stiff tissue, which displays a fibrotic phenotype with relatively low proliferation. In contrast, the soft skin surrounding keloids is exposed to high mechanical strain that correlates with increased expression of the caveolin-1/rho signaling via rho kinase mechanotransduction pathway and elevated inflammation and proliferation, which may lead to keloid progression. CONCLUSIONS: The authors conclude that changes in human position are strongly correlated with mechanical loading of the predilection sites, which leads to increased mechanical strain in the peripheral tissue surrounding keloids. Furthermore, increased mechanical strain in the peripheral tissue, which is the site of keloid progression, was correlated with aberrant expression of caveolin-1/ROCK signaling pathway. These findings suggest a novel mechanism for keloid progression.

[Differential diagnosis of lateral cystic lesions in the knee joint]. / Térdközeli lateralis cystosus elváltozások differenciáldiagnosztikája.

Soft tissues detected on the lateral side of the knee joint may have differential diagnostic difficulties. Although most of these are benign, mostly cystic in appearance, they may raise the clinical suspicion of tumors due to their increased growth. The authors describe two rare soft tissue changes in three patients. They review the diagnostic procedures most commonly used in daily care, present surgical options, and discuss the literature of the subject. Orv Hetil. 2019; 160(15): 593-599.