Prolonged cytopenias after immune effector cell therapy and lymphodepletion in patients with leukemia, lymphoma and solid tumors.

BACKGROUND AIMS: The success of chimeric antigen receptor (CAR) T-cell therapy in treating B-cell malignancies has led to the evaluation of CAR T-cells targeting a variety of other malignancies. Although the efficacy of CAR T-cells is enhanced when administered post-lymphodepleting chemotherapy, this can trigger bone marrow suppression and sustained cytopenia after CD19.CAR T-cell therapy. Additionally, systemic inflammation associated with CAR T-cell activity may contribute to myelosuppression. Cytopenias, such as neutropenia and thrombocytopenia, elevate the risk of severe infections and bleeding, respectively. However, data on the incidence of prolonged cytopenias after immune effector therapy in the solid tumor context remain limited. OBJECTIVE: We compared the incidence of prolonged cytopenias after immune effector therapy including genetically modified T-cells, virus-specific T-cells (VSTs) and NKT-cells, as well non-gene-modified VSTs for leukemia, lymphoma, and solid tumors (ST) to identify associated risk factors. METHODS: A retrospective analysis was conducted of 112 pediatric and adult patients with relapsed and/or refractory cancers who received lymphodepleting chemotherapy followed by immune effector therapy. Patients treated with 13 distinct immune effector cell therapies through 11 single-center clinical trials and 2 commercial products over a 6-year period were categorized into 3 types of malignancies: leukemia, lymphoma and ST. We obtained baseline patient characteristics and adverse events data for each participant, and tracked neutrophil and platelet counts following lymphodepletion. RESULTS: Of 112 patients, 104 (92.9%) experienced cytopenias and 88 (79%) experienced severe cytopenias. Patients with leukemia experienced significantly longer durations of severe neutropenia (median duration of 14 days) compared with patients with lymphoma (7 days) or ST (11 days) (P = 0.002). Patients with leukemia also had a higher incidence of severe thrombocytopenia (74.1%), compared with lymphoma (46%, P = 0.03) and ST (14.3%, P < 0.0001). Prolonged cytopenias were significantly associated with disease type (63% of patients with leukemia, 44% of patients with lymphoma, and 22.9% of patients with ST, P = 0.006), prior hematopoietic stem cell transplant (HSCT) (66.7% with prior HSCT versus 38.3% without prior HSCT, P = 0.039), and development of immune effector cell-associated neurotoxicity syndrome (ICANS) (75% with ICANS versus 38% without ICANS, P = 0.027). There was no significant association between prolonged cytopenias and cytokine release syndrome. CONCLUSIONS: Immune effector recipients often experience significant cytopenias due to marrow suppression following lymphodepletion regardless of disease, but prolonged severe cytopenias are significantly less common after treatment of patients with lymphoma and solid tumors.

Virus-Specific T Cells for the Treatment of Systemic Infections Following Allogeneic Hematopoietic Cell and Solid Organ Transplantation.

Viral infections are a major source of morbidity and mortality in the context of immune deficiency and immunosuppression following allogeneic hematopoietic cell (allo-HCT) and solid organ transplantation (SOT). The pharmacological treatment of viral infections is challenging and often complicated by limited efficacy, the development of resistance, and intolerable side effects. A promising strategy to rapidly restore antiviral immunity is the adoptive transfer of virus-specific T cells (VST). This therapy involves the isolation and ex vivo expansion or direct selection of antigen-specific T cells from healthy seropositive donors, followed by infusion into the patient. This article provides a practical guide to VST therapy by reviewing manufacturing techniques, donor selection, and treatment indications. The safety and efficacy data of VSTs gathered in clinical trials over nearly 30 years is summarized. Current challenges and limitations are discussed, as well as opportunities for further research and development.

Management after acute injury of the anterior cruciate ligament (ACL). Part 3: Recommendation on surgical treatment.

PURPOSE: The aim of this consensus project was to give recommendations regarding surgical treatment of the anterior cruciate ligament (ACL) injured patient. METHODS: For this consensus process, an expert, steering and rating group was formed. In an initial online meeting, the steering group, together with the expert group, formed various key topic complexes for which multiple questions were formulated. For each key topic, a structured literature search was performed by the steering group. The results of the literature review were sent to the rating group with the option to give anonymous comments until a final consensus voting was performed. Sufficient consensus was defined as 80% agreement. RESULTS: During this consensus process, 30 topics regarding the surgical management and technique of ACL reconstruction were identified. The literature search for each key question resulted in 30 final statements. Of these 30 final statements, all achieved consensus. CONCLUSIONS: This consensus process has shown that surgical treatment of ACL injury is a complex process. Various surgical factors influence patient outcomes. The proposed treatment algorithm can be used as a decision aid for the surgeon. LEVEL OF EVIDENCE: Level V.

Mediport use as an acceptable standard for CAR T cell infusion.

Introduction: Mediport use as a clinical option for the administration of chimeric antigen receptor T cell (CAR T cell) therapy in patients with B-cell malignancies has yet to be standardized. Concern for mediport dislodgement, cell infiltration, and ineffective therapy delivery to systemic circulation has resulted in variable practice with intravenous administration of CAR T cell therapy. With CAR T cell commercialization, it is important to establish practice standards for CAR T cell delivery. We conducted a study to establish usage patterns of mediports in the clinical setting and provide a standard of care recommendation for mediport use as an acceptable form of access for CAR T cell infusions. Methods: In this retrospective cohort study, data on mediport use and infiltration rate was collected from a survey across 34 medical centers in the Pediatric Real-World CAR Consortium, capturing 504 CAR T cell infusion routes across 489 patients. Data represents the largest, and to our knowledge sole, report on clinical CAR T cell infusion practice patterns since FDA approval and CAR T cell commercialization in 2017. Results: Across 34 sites, all reported tunneled central venous catheters, including Broviac® and Hickman® catheters, as accepted standard venous options for CAR T cell infusion. Use of mediports as a standard clinical practice was reported in 29 of 34 sites (85%). Of 489 evaluable patients with reported route of CAR T cell infusion, 184 patients were infused using mediports, with no reported incidences of CAR T cell infiltration. Discussion/Conclusion: Based on current clinical practice, mediports are a commonly utilized form of access for CAR T cell therapy administration. These findings support the safe practice of mediport usage as an accepted standard line option for CAR T cell infusion.

Shadow imaging for panoptical visualization of brain tissue in vivo.

Progress in neuroscience research hinges on technical advances in visualizing living brain tissue with high fidelity and facility. Current neuroanatomical imaging approaches either require tissue fixation (electron microscopy), do not have cellular resolution (magnetic resonance imaging) or only give a fragmented view (fluorescence microscopy). Here, we show how regular light microscopy together with fluorescence labeling of the interstitial fluid in the extracellular space provide comprehensive optical access in real-time to the anatomical complexity and dynamics of living brain tissue at submicron scale. Using several common fluorescence microscopy modalities (confocal, light-sheet and 2-photon microscopy) in mouse organotypic and acute brain slices and the intact mouse brain in vivo, we demonstrate the value of this straightforward 'shadow imaging' approach by revealing neurons, microglia, tumor cells and blood capillaries together with their complete anatomical tissue contexts. In addition, we provide quantifications of perivascular spaces and the volume fraction of the extracellular space of brain tissue in vivo.

Editorial Commentary: Bony Morphology Determines the Extent of Concomitant Injuries in Anterior Cruciate Ligament Injured Knees.

The bony morphology of both tibia and femur has been found to influence the risk of anterior cruciate ligament (ACL) injuries. Quantifying the femoral condylar's sagittal morphology, the lateral femoral condyle ratio (LFCR) has been associated with injuries to the anterolateral knee joint capsule, including the anterolateral ligament in ACL-injured knees. Rotational instability may be in part attributable to femoral anisometry with an increase of the LFCR contributing to increased laxity and risk for ACL ruptures as well as concomitant injuries. While there is currently no surgical treatment available to change the bony morphology of the femur, possibilities such as the addition of a lateral extra-articular tenodesis, adjustment of graft selection, or modification of surgical techniques may mitigate the risk of ACL rerupture in patients with a high LFCR.

Posoleucel, an Allogeneic, Off-the-Shelf Multivirus-Specific T-Cell Therapy, for the Treatment of Refractory Viral Infections in the Post-HCT Setting.

PURPOSE: Viral infections are a major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). In the absence of safe and effective antiviral treatments, virus-specific T cells have emerged as a promising therapeutic option. Posoleucel is a multivirus-specific T-cell therapy for off-the-shelf use against six viral infections that commonly occur in allo-HCT recipients: adenovirus, BK virus (BKV), cytomegalovirus, Epstein-Barr virus, human herpes virus-6, and JC virus. PATIENTS AND METHODS: We conducted an open-label, phase II trial to determine the feasibility and safety of posoleucel in allo-HCT recipients infected with one or more of these viruses. Infections were either unresponsive to or patients were unable to tolerate standard antiviral therapies. Fifty-eight adult and pediatric patients were enrolled and treated. RESULTS: Posoleucel was well tolerated, with no cytokine release syndrome or other infusion-related toxicities; two patients (3.4%) developed Grade 2 and one patient (1.7%) Grade 3 GvHD during the trial. The overall response rate 6 weeks after the first posoleucel infusion was 95%, with a median plasma viral load reduction of 97%. Of the 12 patients who had two or more target viral infections identified at study entry, 10 (83%) had a clinical response for all evaluable viruses. Of the 23 patients treated for refractory BKV-associated hemorrhagic cystitis, 74% had resolution of symptoms and macroscopic hematuria by 6 weeks post-infusion. CONCLUSIONS: In this open-label trial, treatment of refractory viral infections/disease in allo-HCT recipients with posoleucel was feasible, safe, and effective.

Current status of the management of isolated syndesmotic injuries in Germany.

INTRODUCTION: Although non-fracture-related syndesmotic injuries of the ankle are relatively rare, they may lead to poor clinical outcome if initially undiagnosed or managed improperly. Despite a variety of literature regarding possibilities for treatment of isolated syndesmotic injuries, little is known about effective applications of different therapeutic methods in day-to-day work. The aim of this study was to assess the current status of the treatment of isolated syndesmotic injuries in Germany. MATERIALS AND METHODS: An online-questionnaire, capturing the routine diagnostic workup including clinical examination, radiologic assessment and treatment strategies, was sent to all members of the German Society of Orthopedic Surgery and Traumatology (DGOU) and Association of Arthroscopic and Joint Surgery (AGA). Statistical analysis was performed using Microsoft excel and SPSS. RESULTS: Each question of the questionnaire was on average answered by 431 ± 113 respondents. External rotation stress test (66%), squeeze test (61%) and forced dorsiflexion test (40%) were most commonly used for the clinical examination. In the diagnostic workup, most clinicians relied on MRI (83%) and conventional X-ray analysis (anterior-posterior 58%, lateral 41%, mortise view 38%). Only 15% of the respondents stated that there is a role for arthroscopic evaluation for the assessment of isolated syndesmotic injuries. Most frequently used fixation techniques included syndesmotic screw fixation (80%, 42% one syndesmotic screw, 38% two syndesmotic screws), followed by suture-button devices in 13%. Syndesmotic screw fixation was mainly performed tricortically (78%). While 50% of the respondents stated that syndesmotic screw fixation and suture-button devices are equivalent in the treatment of isolated syndesmotic injuries with respect to clinical outcome, 36% answered that syndesmotic screw fixation is superior compared to suture-button devices. CONCLUSIONS: While arthroscopy and suture-button devices do not appear to be widely used, syndesmotic screw fixation after diagnostic work-up by MRI seems to be the common treatment algorithm for non-fracture-related syndesmotic injuries in Germany.

Management of nutritional iron deficiency anemia for young children in the emergency department.

BACKGROUND: Guidelines for young children with nutritional iron deficiency anemia (IDA) presenting to the emergency department (ED) are lacking, leading to variability in care. We aimed to standardize management of these patients through the development and implementation of an evidence-based algorithm using quality improvement methodology. PROCEDURE: Baseline data of the target population (n = 42; 60% male; median age 22.5 months, median hemoglobin 5.3 g/dl) identified variability across four key measures of clinical management: laboratory evaluation, therapy choice, therapy administration, and patient disposition. Literature review and consensus from pediatric hematology providers informed a draft algorithm that was refined in an iterative multidisciplinary process. From September 2020 to June 2021, we aimed to increase IDA management per the algorithm by ≥20% relative to baseline for the four key outcome measures using sequential Plan-Do-Study-Act (PDSA) cycles. Process measures focusing on provider communication/documentation and balancing measures involving efficiency and therapy-related adverse events were assessed concurrently. RESULTS: Thirty-five patients were evaluated among four PDSA cycles and shared similar characteristics as the baseline population. Improvements of ≥20% above baseline adherence levels or 100% adherence were achieved for all outcome measure across four PDSA cycles. Adherence to recommended laboratory evaluation improved from 43 (baseline) to 71%, therapy choice from 78 to 100%, therapy administration from 50 to 83%, and disposition from 85 to 100%. ED length of stay remained stable. CONCLUSIONS: Implementation of a standardized algorithm for young children with nutritional IDA in the ED increased adherence to evidence-based patient care.

[Future implications of navigation in total knee arthroplasty]. / Gibt es noch Gründe für die Navigation in der Knieendoprothetik?

BACKGROUND: After more than two decades of experience with computer-assisted knee arthroplasty, extensive experience and study data are available, allowing a profound evaluation. Undoubtedly, computer-assisted knee arthroplasty has been proven to achieve excellent results for implant positioning and long-leg axis reconstruction. Thus, computer-assisted knee arthroplasty represents the current gold standard to avoid unintended malpositioning of total knee components for neutrally aligned implants and individualized implant alignment (kinematic alignment, adjusted mechanical alignment, and others). Previous studies could not show significant differences in functional outcomes and patient satisfaction. However, recent meta-analyses showed relevant advantages of computer-assisted knee arthroplasty. These results could be based on further developments in software-assisted soft tissue balancing and more sensitive evaluation methods of follow-up examinations. LONG-TERM OUTCOME: Further, international registries show advantages of computer-assisted knee arthroplasty regarding long-term outcomes. In particular, the Australian arthroplasty registry describes a significantly lower revision rate due to aseptic loosening/osteolysis in the computer-assisted knee arthroplasty group, analyzing a period of up to 17 years. These positive effects can already be proven six months following surgery. FUTURE PROSPECTS: However, despite demonstrated benefits, computer-assisted knee arthroplasty has not yet become established in daily routine, and wide regional variations in its use are observed. Newer developments such as robotic-assisted knee arthroplasty, primarily based on navigation techniques, are currently being heavily promoted. However, this new technology must justify its enormous additional costs and prove its advantages compared to computer-assisted knee arthroplasty. In the backdrop of the development of computer-assisted knee arthroplasty, this might be a difficult task.

A Costimulatory CAR Improves TCR-based Cancer Immunotherapy.

T-cell receptors (TCR) recognize intracellular and extracellular cancer antigens, allowing T cells to target many tumor antigens. To sustain proliferation and persistence, T cells require not only signaling through the TCR (signal 1), but also costimulatory (signal 2) and cytokine (signal 3) signaling. Because most cancer cells lack costimulatory molecules, TCR engagement at the tumor site results in incomplete T-cell activation and transient antitumor effects. To overcome this lack of signal 2, we genetically modified tumor-specific T cells with a costimulatory chimeric antigen receptor (CoCAR). Like classical CARs, CoCARs combine the antigen-binding domain of an antibody with costimulatory endodomains to trigger T-cell proliferation, but CoCARs lack the cytotoxic CD3ζ chain to avoid toxicity to normal tissues. We first tested a CD19-targeting CoCAR in combination with an HLA-A*02:01-restricted, survivin-specific transgenic TCR (sTCR) in serial cocultures with leukemia cells coexpressing the cognate peptide-HLA complex (signal 1) and CD19 (signal 2). The CoCAR enabled sTCR+ T cells to kill tumors over a median of four additional tumor challenges. CoCAR activity depended on CD19 but was maintained in tumors with heterogeneous CD19 expression. In a murine tumor model, sTCR+CoCAR+ T cells improved tumor control and prolonged survival compared with sTCR+ T cells. We further evaluated the CoCAR in Epstein-Barr virus-specific T cells (EBVST). CoCAR-expressing EBVSTs expanded more rapidly than nontransduced EBVSTs and delayed tumor progression in an EBV+ murine lymphoma model. Overall, we demonstrated that the CoCAR can increase the activity of T cells expressing both native and transgenic TCRs and enhance antitumor responses.

Arthroscopic Screw Fixation Technique for Transverse Glenoid Fractures.

Transverse glenoid fractures with a cranial coracoglenoidal fragment (Ideberg type III) can lead to detrimental post-traumatic sequelae. Open surgery requires an extensive surgical approach. Arthroscopic procedures are highly challenging with respect to both fracture reduction and screw osteosynthesis. We present a reproducible arthroscopic technique for a dislocated transverse glenoid fracture using 5 standard portals. Grasping the coracoid with a small, serrated reduction clamp through the anterior portal allows simple and sufficient reduction. Safe screw osteosynthesis can then be performed from cranially without the need to create a Neviaser portal.

COVID-19 outcomes in a large pediatric hematology-oncology center in Houston, Texas.

An understanding of the behavior of SARS-CoV-2 in pediatric hematology-oncology patients is essential to the optimal management of these patients during the COVID-19 pandemic. This study describes the characteristics and outcomes of COVID-19 disease in children with cancer or hematologic disorders treated at a large children's hospital. A retrospective cohort study was conducted at Texas Children's Cancer and Hematology Center from January 1, 2020 to September 30, 2020. All patients with a primary hematology-oncology diagnosis and SARS-CoV-2 positivity by reverse transcription polymerase chain reaction were identified. Clinical and laboratory data were obtained from the medical record. Descriptive analyses were performed to evaluate COVID-19-related outcomes and risk factors for severe disease in this population. We identified 109 patients with COVID-19 disease, including 52 hematology, 51 oncology, and 6 HSCT patients; median age was 10.3 years (IQR 4.4-15.9), and 58.7% were male. Seventy-four percent of the patients were managed in the outpatient setting. Patients with sickle cell disease were more likely to require hospitalization. ICU care was needed in 8% (n = 9) of the entire cohort, and mechanical ventilation was required in 6.4% (6 oncology patients, 1 hematology patient). COVID-19 contributed to the deaths of two cancer patients. No deaths occurred in hematology or HSCT patients. In conclusion, the risk of severe COVID-19 complications is slightly higher in pediatric hematology-oncology patients than in the general pediatric population but lower than initially feared. For most asymptomatic patients, primary disease management may continue as planned, but treatment decisions must be individualized.

Editorial Commentary: Vancomycin Soaking of the Graft in Anterior Cruciate Ligament Reconstruction: A Concept on the Way to Becoming the New Gold Standard.

An increasing number of surgeons adopt the concept of vancomycin soaking of the graft in anterior cruciate ligament reconstruction and report drastically reduced numbers of postoperative septic knee arthritis. This reduction of incidence is supported by in vitro data, showing no influence of vancomycin on tendon material properties. Although the applied antibiotic concentration has reported to be potent in eradicating graft contamination, no evidence of chondrotoxicity has been shown. Based on the increasing evidence, the call for randomized controlled trials stands in ethical contrast with the medical responsibility not to withhold patients an infection prophylaxis that has already been proven to be safe and effective.

Patient-Reported and Quantitative Outcomes of Anatomic Anterior Cruciate Ligament Reconstruction With Hamstring Tendon Autografts.

BACKGROUND: The pivot-shift test has become more consistent and reliable and is a meaningful outcome measurement after anterior cruciate ligament reconstruction (ACLR). PURPOSE/HYPOTHESIS: The purpose of this investigation was to assess patient-reported outcomes (PROs) and the quantitative pivot shift (QPS) preoperatively, at time zero immediately after anatomic ACLR, and after 24 months as well as the relationship between PROs and the QPS. It was hypothesized that anatomic ACLR would restore rotatory stability measured by the pivot-shift test and that QPS measurements would be positively correlated with PROs. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: The ACL-injured and contralateral uninjured knees from 89 of 107 (83.2%) enrolled patients at 4 international centers were evaluated using a standardized pivot-shift test. Tibial acceleration was assessed with an inertial sensor, and lateral compartment translation was measured using an image analysis system preoperatively, at time zero immediately postoperatively, and at follow-up after 2 years. PROs were assessed at 12 and 24 months postoperatively with the International Knee Documentation Committee (IKDC) subjective knee form, Cincinnati Knee Rating System (CKRS), Marx activity rating scale, and activity of daily living score (ADLS). RESULTS: The mean patient age at surgery was 27 years (range, 15-45 years). A positive pivot shift preoperatively (side-to-side difference in tibial acceleration, 2.6 ± 4.0 m/s2; side-to-side difference in anterior tibial translation, 2.0 ± 2.0 mm) was reduced at time zero postoperatively (side-to-side difference in tibial acceleration, -0.5 ± 1.3 m/s2; side-to-side difference in anterior tibial translation, -0.1 ± 1.0 mm). All PROs improved from preoperatively to final follow-up at 24 months: from 56.5 to 85.5 points for the IKDC (P = .0001), from 28.8 to 32.4 points for the CKRS (P = .04), from 11.2 to 7.9 points for the Marx (P < .0001), and from 75.7 to 91.6 points for the ADLS (P < .0001). Neither preoperative nor time zero postoperative rotatory laxity assessed by the pivot-shift test correlated with PROs at 24-month follow-up. A graft retear was observed in 4 patients (4.5%) within 2 years of follow-up. CONCLUSION: Anatomic ACLR resulted in significantly improved and acceptable PROs at 2-year follow-up and a low failure rate. Anatomic ACLR restored QPS measurements of anterior tibial translation and tibial acceleration to those of the contralateral knee immediately after surgery while still under anesthesia, but there was no correlation between the QPS preoperatively or at time zero after ACLR and PROs at 2-year follow-up.

High variability of tibial slope measurement methods in daily clinical practice: Comparisons between measurements on lateral radiograph, magnetic resonance imaging, and computed tomography.

BACKGROUND: Tibial slope measurements are important in guiding clinical decisions in the field of orthopedic surgery. However, there are multiple techniques across different medical imaging modalities and little is known about its impact on result and validity of the measurement. Therefore, the purpose of this study was to compare tibial slope measurements from lateral radiographs, magnetic resonance imaging (MRI) and computed tomography (CT) scans in order to better assess the clinical significance of measured tibial slope values. METHODS: Twenty patients with complete medical imaging (lateral radiographs, MRI, CT scans) undergoing anterior cruciate ligament revision surgery were included. The tibial slope of the medial and lateral plateau were measured and compared using the methods of Dejour et al. and Utzschneider et al. on lateral radiographs, by Hudek et al. and Hashemi et al. on MRI and CT scans, and by Zhang et al. on three-dimensional reconstructions of CT scans. RESULTS: Mean differences up to 5.4 ± 2.8° (P < 0.05) and 4.9 ± 2.6° (P < 0.05) between different measurement methods were found for the medial and lateral tibial slope, respectively. Depending on how the tibial shaft axis was defined, significant differences between the respective measurement methods and a relevant degree of variability were identified. Pearson correlation coefficients between the measurement methods varied distinctly from moderate to strong correlations. CONCLUSIONS: Tibial slope measurements have a high degree of variability and inaccuracy between imaging modalities and different measurement methods. Care must be taken when deciding on indications based on individual modality measurements.

Tactile techniques are associated with a high variability of tunnel positions in lateral extra-articular tenodesis procedures.

INTRODUCTION: The purpose of this study was to determine the variability of femoral tunnel positions applying two different lateral extra-articular tenodesis (LET) techniques, guiding on the tactile identification (1) of the lateral epicondyle (Lemaire procedure) and (2) of the Kaplan fibre attachments on the distal femur (MacIntosh procedure) and to analyse whether one of these procedures is more suitable for reliable femoral tunnel positioning in LET procedures. MATERIALS AND METHODS: Two experienced knee surgeons determined femoral tunnel positions in ten fresh-frozen cadaveric knee specimens according to the modified Lemaire and MacIntosh techniques. Tunnel positions were measured on true lateral radiographs as absolute distances from the posterior cortex line (anterior-posterior direction) and from a perpendicular line intersecting the contact of the posterior femoral condyle (proximal-distal direction), respectively. Further, tunnel positions were measured relatively to the femur height. An independent F test was used to compare variances between Lemaire and MacIntosh tunnel positions and between anterior-posterior and proximal-distal directions. RESULTS: The mean Lemaire and MacIntosh positions were found 2.7 ± 5.5 mm and 3.6 ± 3.4 mm anterior to the posterior cortex line, and 7.5 ± 5.0 mm and 17.3 ± 6.9 mm proximal to the perpendicular line intersecting the contact of the posterior femoral condyle, respectively. Mean Lemaire and MacIntosh positions, relative to the femur height, were found at 8.8% and 10.9% (anterior-posterior) and 22.2% and 50.8% (proximal-distal), respectively. Variability in tunnel positioning was observed for both techniques, showing no significant differences in the variance (p > 0.05) and partially overlapping tunnel positions of both techniques. The overall variance of tunnel positions, however, was significantly greater in proximal-distal than in anterior-posterior direction (F = 2.673, p < 0.038). CONCLUSIONS: Femoral tunnel positions in LET procedures have a high degree of variability and inaccuracy. Palpating anatomic landmarks appears to be insufficient to generate reproducible tunnel positions. Radiographic landmarks may enable more reproducible identification of isometric femoral tunnel positions and reduce malpositioning.

Vancomycin-soaking of the graft reduces the incidence of septic arthritis following ACL reconstruction: results of a systematic review and meta-analysis.

PURPOSE: (1) To compare the incidence of post-operative septic arthritis following anterior cruciate ligament reconstruction (ACLR) between patients receiving routine pre-operative intravenous (IV) prophylaxis only intravenous (IV) infection prophylaxis and patients receiving additional graft-soaking in a vancomycin solution (5 mg/ml) perioperatively. (2) To review the literature regarding effects of graft-soaking in vancomycin solutions on outcomes, complication rates and tendon properties in ACLR. METHODS: To identify studies pertaining to routine pre-operative IV prophylaxis and additional usage of intra-operative vancomycin-soaked grafts in primary ACLR, the Cochrane Library, SCOPUS and MEDLINE were searched till June 2018 for English and German language studies of all levels of evidence following the PRISMA guidelines. Additionally, all accepted abstracts at the ESSKA 2018, ISAKOS 2017, AGA 2017 and AOSSM 2017 meetings were screened. Data regarding the incidence of septic arthritis were abstracted and combined in a meta-analysis. Data including outcome scores, complication rates and in vitro analyses of tendon properties were collected and summarized descriptively. RESULTS: Upon screening 785 titles, 8 studies were included. These studies examined 5,075 patients following ACLR and followed from 6 to 52 weeks post-operatively. Of those 2099 patients in the routine pre-operative IV prophylaxis group, 44 (2.1%) cases of early septic arthritis were reported. In contrast, there were no reports of septic arthritis following ACLR in 2976 cases of vancomycin-soaked grafts. The meta-analysis yielded an odds ratio of 0.04 (0.01-0.16) favouring the addition of intra-operative vancomycin-soaking of grafts. Across all available studies, no differences in clinical outcome (i.e. incidence of ACL revision, IKDC score, Tegner score), biomechanical tendon properties, or cartilage integrity between patients with and without vancomycin-soaked grafts were identified. CONCLUSION: The incidence of septic arthritis following ACLR can be reduced dramatically by vancomycin-soaking the grafts intra-operatively prior to graft passage and fixation. Within the limitation confines of this study, intra-operative graft-soaking in vancomycin appears to be a safe and effective method to reduce the incidence of septic arthritis following ACLR. Still, it remains debatable if the available data facilitate the recommendation for a universal application of vancomycin-soaking for all ACLR patients or if it should be reserved for patients at risk, including the use hamstring tendons, revision cases and in the presence of medical preconditions. LEVEL OF EVIDENCE: Level IV, systematic review of Level III and Level IV studies.