Anterior cruciate ligament remnant tissue harvested within 3-months after injury predicts higher healing potential.

BACKGROUND: No study has examined the possible factors associated with different characteristics of stem-like cells derived from anterior cruciate ligament (ACL) remnants. And the purpose of the study is to elucidate whether demographic factors are associated with healing potential of stem-like cells derived from the ACL remnants tissue. METHODS: Thirty-six ACL remnants were harvested from patients who received primary arthroscopic ACL reconstruction. Interval from injury to surgery, age, sex, and combined meniscal or chondral injuries were analyzed. Cells were isolated from remnant tissues and their healing potential was evaluated by: 1) characterization of surface markers (CD34, CD44, CD45, CD146, CD29, and Stro-1), 2) cell expansion, 3) osteogenic differentiation, and 4) endothelial differentiation. Finally, using multivariable logistic regression to evaluate the relation between demographic factors and healing potential parameters. Adjusted odds ratios (OR) were calculated, and the significant difference was set at p < 0.05. RESULTS: ACL remnant tissue harvested less than 90 days after injury predicted higher fractions of stem-like cells [CD34+ (OR = 6.043, p = 0.025), CD44 + (OR = 8.440, p = 0.011), CD45+ (OR = 16.144, p = 0.015), and CD146+ (OR = 9.246, p = 0.015)] and higher expansion potential (passage 3: OR = 9.755, p = 0.034; passage 10: OR = 33.245, p = 0.003). Regarding osteogenic differentiation, higher gene expression of Osteocalcin (OR = 22.579, p = 0.009), Alkaline phosphatase (OR = 6.527, p = 0.022), and Runt-related transcription factor 2 (OR = 5.247, p = 0.047) can also be predicted. Younger age predicted higher CD34+ levels (20 ≤ age < 30 years, OR = 2.020, p = 0.027) and higher expansion potential at passage 10 (10 ≤ age < 20 years, OR = 25.141, p = 0.026). There was no significant relation found between meniscal or chondral injuries and ACL healing potential. CONCLUSION: Our results indicated that the ACL remnant tissue harvested within 3-months after injury yields higher healing potential, suggesting early surgical intervention may achieve better clinical results.

Ampicillin/sulbactam versus cefazolin plus aminoglycosides for antimicrobial prophylaxis in management of Gustilo type IIIA open fractures: A retrospective cohort study.

BACKGROUND: The antibiotic regimens for prophylaxis in the management of open fractures remain controversial. Although the use of aminoglycosides is widely accepted for treatment of Gustilo type III open fractures, aminoglycosides are often avoided in patients with risk factors. This study aimed to compare efficacy and safety of two regimens, cephazolin plus aminoglycoside (amikacin or gentamicin) and ampicillin/sulbactam (ABPC/SBT), in patients with Gustilo type IIIA open fractures. METHODS: A total of 95 Gustilo type IIIA fractures in 90 patients were retrospectively reviewed in this study. The cohort was categorized into two groups that were treated in accordance with the institutional prescribed regimen in different periods: (1) cefazolin plus aminoglycoside (January 1, 2014-September 30, 2017) and (2) ABPC/SBT monotherapy (October 1, 2017-September 30, 2020). Cefazolin was used at 1-2 g every 8 h, aminoglycoside (amikacin or gentamicin) was used daily depending on body weight, and ABPC/SBT was used at 3 g every 8 h The antibiotic administration was continued within 3 days or until successful soft tissue coverage was achieved. The infection rate and the incidence of acute kidney injury (AKI) in both groups were assessed. RESULTS: ABPC/SBT was used in 34 patients (36 fractures), and 56 patients (59 fractures) received cefazolin plus aminoglycoside for antibiotic prophylaxis. Infection developed in 2 of 36 fractures in ABPC/SBT group and 4 of 59 fractures in the cefazolin plus aminoglycoside group (p > 0.99). The average serum creatinine levels on admission, baseline, and peak during the hospital stay were not significantly different between the two groups. One case of AKI was identified in each group, indicating that incidence rate of AKI was not significantly different between the two groups. CONCLUSION: We demonstrated the non-inferiority of ABPC/SBT therapy over cefazolin plus aminoglycoside regimen for type IIIA open fractures. The ABPC/SBT regimen may be an alternative option for managing Gustilo type IIIA open fractures. Further prospective studies with larger samples are needed to verify these results.

Completion of the full-length genome sequence of human parainfluenza virus types 4A and 4B: sequence analysis of the large protein genes and gene start, intergenic and end sequences.

We have already reported the nucleotide sequences of the NP, P/V, M, F and HN genes of human parainfluenza virus type 4A (hPIV-4A) and type 4B (hPIV-4B). Here, we have determined the sequences of the L protein genes as well as the gene start, intergenic and end sequences, thereby completing the full-length genome sequence of hPIV-4A and 4B. hPIV-4A and 4B have 17,052 and 17,304 nucleotides, respectively. The end sequence of hPIV-4, especially 4B, was extraordinarily long. In a comparison with members of the genus Rubulavirus, the hPIV-4 L proteins were closely related to those of mumps virus (MUV) and hPIV-2, less closely related to those of Menangle virus and Tioman virus, and more distantly related to those of Mapuera virus and porcine rubulavirus.

The Influence of Ruptured Scar Pattern on the Healing Potential of Anterior Cruciate Ligament Remnant Cells.

BACKGROUND: Vascular CD34+ cells in anterior cruciate ligament (ACL) tissues have a potential for high proliferation and multilineage differentiation, which can accelerate tendon-bone healing after ACL reconstruction. To predict outcomes of ACL reconstruction with remnant preservation or ruptured tissue incorporation, patient characteristics should be considered. However, the influence of ACL remnant morphologic pattern on healing potential remains unknown. HYPOTHESIS: The healing potential of ACL remnants could differ among their morphologic patterns. STUDY DESIGN: Descriptive laboratory study. METHODS: ACL remnant tissues were harvested from patients aged <35 years who received primary ACL reconstruction within 3 months after injury. The tissues were evaluated according to the Crain classification (4 patterns). The patterns were divided into 2 groups: the reattachment group (Crain I-III) and the nonreattachment group (Crain IV). ACL remnant cells were characterized via fluorescence-activated cell sorting. The potential for proliferation and multilineage differentiation was assessed and compared between the groups. RESULTS: The ratio of CD34+ cells was significantly higher in the nonreattachment group than in the reattachment group. In early passages, the nonreattachment group had a significantly higher expansion potential than the reattachment group. In the evaluation of osteogenic and endothelial differentiation potential, the nonreattachment group showed a higher potential in immunohistochemical/histochemical staining and quantitative real-time polymerase chain reaction analysis as compared with the reattachment group. CONCLUSION: In the subacute phase, ACL remnant tissue of the nonreattachment group possibly has a higher healing potential than that of the reattachment group. CLINICAL RELEVANCE: If healing potential differs among the morphologic patterns of ACL remnants, surgeons may expect the healing potential when preserving remnants.

Joint gap assessment with a tensor is useful for the selection of insert thickness in unicompartmental knee arthroplasty.

BACKGROUND: The success of unicompartmental knee arthroplasty relies on a lot of factors such as correct osteotomy and proper soft-tissue tensioning. A selection of insert thickness depends solely on the surgeon's subjective feeling. Recently, a tensor that is designed to assess soft tissue balance during unicompartmental knee arthroplasty has been developed. The purpose of this study was to compare the component gap throughout the range of motion among different distraction forces and examine the correlation between the component gap and the insert thickness. METHODS: 30 cases of 29 patients were included. All the patients received a conventional medial Zimmer Unicompartmental High Flex Knee System. Using a tensor under 10, 20, 30, and 40 lb distraction forces, after femoral component placement, the component gaps were assessed throughout the range of motion. The correlations between the component gap and the insert thickness selected were examined. FINDINGS: The component gap showed the same kinematic pattern among the different distraction forces and the value increased in proportion to the increase of the distraction force in unicompartmental knee arthroplasty. The insert thickness in unicompartmental knee arthroplasty was found to have a strong positive correlation with the component gap from 10 to 45° of knee flexion with a distraction force of more than 20 lb INTERPRETATION: With the use of the tensor, surgeons can quantify the component gap and objectify their insert thickness decision compared with the use of tension gauge.

Age-dependent healing potential of anterior cruciate ligament remnant-derived cells.

BACKGROUND: The anterior cruciate ligament (ACL) does not heal spontaneously after injury, and ACL patients of different ages respond differently to treatment. Although ACL-derived CD34-positive cells contribute to bone-tendon healing after ACL reconstruction, the relationship between the healing potential of ACL-derived cells and a patient's age is unknown. HYPOTHESIS: ACL-derived cells from young patients will have a greater effect on the maturation of bone-tendon integration in an immunodeficient rat model of ACL reconstruction compared with cells derived from older patients. STUDY DESIGN: Controlled laboratory study. METHODS: Sixty 10-week-old female immunodeficient rats underwent ACL reconstruction (using the autologous flexor digitorum longus tendon as a graft) followed by intracapsular administration of ACL-derived cells from patients aged 10 to 19 years (younger group) or patients aged 30 to 39 years (older group), or they were given phosphate-buffered saline (PBS; PBS group). Histologic, radiographic, and biomechanical examinations were performed 2 to 8 weeks after surgery. In addition, intrinsic and human cell-derived angiogenesis and osteogenesis were examined by immunohistochemistry. RESULTS: In the younger group, histologic assessment demonstrated early bone-tendon healing, which induced endochondral ossification-like integration. Micro-computed tomography showed a statistically significant reduction in the area of tibial bone tunnel in the younger group (week 4, 20.0% ± 11.2% reduction; week 8, 25.7% ± 5.6% reduction) compared with the older group (week 4, 1.8% ± 3.0% reduction; week 8, 4.0% ± 5.9% reduction) and the PBS group (week 4, -0.5% ± 3.2% reduction; week 8, 3.3% ± 5.2% reduction) (week 4, P < .05; week 8, P < .01). Failure loads during tensile testing demonstrated a significantly higher ultimate load to failure in the younger group (17.52 ± 4.01 N) compared with the older (8.05 ± 2.91 N) and PBS (7.01 ± 3.16 N) groups (P < .05), and isolectin B4 and rat osteocalcin immunostaining indicated enhanced intrinsic angiogenesis and osteogenesis in the younger group. There was no statistically significant difference in the results of radiographic and biomechanical examinations between the older and PBS groups. Double immunohistochemistry for human-specific endothelial cell and osteoblast markers demonstrated a greater ability of differentiation into endothelial cells and osteoblasts in the younger group. CONCLUSION: ACL-derived cells from younger patients enhanced early bone-tendon healing in an immunodeficient rat model of ACL reconstruction. CLINICAL RELEVANCE: Surgeons should consider a patient's age when performing ACL reconstruction with remnant preservation or ruptured tissue incorporation, as this can predict healing ability.

Age-Related Differences in Anterior Cruciate Ligament Remnant Vascular-Derived Cells.

BACKGROUND: The anterior cruciate ligament (ACL) does not heal spontaneously after injury, and patients of different ages respond differently to treatment. CD34+ stem/progenitor cells derived from the ACL remnant and associated tissues contribute to tendon-bone healing, but the relationship between age and the ACL's healing potential has not been clarified. HYPOTHESIS: The ACL remnant and associated tissues from adolescent patients have more CD34+ cells, and this population of cells from younger patients exhibits a higher potential for proliferation and differentiation in vitro. STUDY DESIGN: Descriptive laboratory study. METHODS: Ruptured ACL remnants and associated tissues were harvested from 28 patients (mean age, 24.6 ± 1.6 years) who had undergone primary arthroscopic ACL reconstruction. Patients were divided into 3 patient groups by age: 10-19 years (teens group; n = 10), 20-29 years (20s group; n = 10), and ≥30 years (30s group; n = 8). The ACL remnant cells were characterized using fluorescence-activated cell sorting (FACS). Expansion potential was evaluated using population doubling (PD), and multilineage differentiation potential was assessed and compared. RESULTS: The FACS analysis showed numerous CD34+ cells in the teens group compared with the 30s group (mean, 25.4% ± 7.9% vs 16.9% ± 3.9%, respectively; P = .044). The PD results indicated that the teens group had a significantly higher expansion potential than the 30s group at passage 3 (mean, 3.3 ± 0.2 vs 2.8 ± 0.2, respectively; P = .039). Young ACL remnant cells had a higher potential for osteogenic differentiation according to alkaline phosphatase activity (teens group, 169.5 ± 37.9 × 10 ng/mL vs 30s group, 64.9 ± 14.6 × 10 ng/mL; P = .029) and osteocalcin gene expression (teens group, 1.0 ± 0.25 vs 30s group, 0.39 ± 0.01; P = .01). In addition, the teens group displayed a higher differentiation potential to angiogenic lineages (acetylated low-density lipoprotein/Ulex europaeus lectin-stained cell counts) than other groups (teens group, 15.9 ± 1.9 vs 20s group, 8.9 ± 1.3 [P = .04]; teens group, 15.9 ± 1.9 vs 30s group, 7.2 ± 1.5 [P = .008]) and also tube length (teens group, 6939 ± 470 µm vs 30s group, 4119 ± 507 µm; P = .009). CONCLUSION: The ACL remnants of adolescent patients had more CD34+ cells, and those cells had a higher potential for proliferation and multilineage differentiation in vitro. CLINICAL RELEVANCE: During remnant-preserving or remnant-transplanted ACL reconstruction, surgeons should consider the patient's age when predicting the healing potential.