ACL reconstruction using 5- or 6-strand hamstring autograft provides graft's diameter bigger than 8 mm.

PURPOSE: The objective of this study was to measure the diameters of 5- and 6-strand hamstring autografts and to evaluate the predictability of their thickness by other body size indices. METHODS: Data were collected from 122 skeletally mature adult patients, who had undergone arthroscopic anterior cruciate ligament reconstruction using only 5- or 6-strand hamstring autografts. The diameters of tibial and femoral ends of the grafts were measured with the precision of 0.5 mm. Multiple linear regression was performed to determine the relationship between autograft's thickness and body size indices. RESULTS: The diameter of the femoral end of the 5-strand graft in male/female patients on average was 8.9/8.3 mm, while the femoral end of the 6-strand graft-9.3/8.5 mm (respectively). In 98.4% of the cases, 5- or 6-strand hamstring autografts were significantly thicker than 8 mm. In 5-strand group, a significant positive correlation was detected between the diameter of autograft's femoral end and patient's height (r = 0.55; p < 0.001), weight (r = 0.60; p < 0.001) and BMI (r = 0.43; p < 0.01). The 6-strand group had statistically significant correlations between the femoral end of the graft and height (r = 0.53; p < 0.001), and femoral end of the graft and weight (r = 0.50; p < 0.001). CONCLUSIONS: Hamstring autografts were significantly thicker than 8 mm. Taller and heavier persons tended to have greater diameters of hamstring autografts; however, to better predict the diameter of autograft, body composition should be studied in relation to autograft's size. Preparation of 5- or 6-strand graft (using all the length of hamstring tendons) provides almost 100% of probability to obtain graft's diameter bigger than 8 mm. LEVEL OF EVIDENCE: Level III.

Short-chain mono-carboxylates as negative modulators of allosteric transitions in Gloeobacter violaceus ligand-gated ion channel, and impact of a pre-ß5 strand (Loop Ω) double mutation on crotonate, not butyrate effect.

Using the bacterial proton-activated pentameric receptor-channel Gloeobacter violaceus ligand-gated ion channel (GLIC): (1) We characterize saturated, mono-carboxylates as negative modulators of GLIC (as previously shown for crotonate; Alqazzaz et al., Biochemistry, 2016, 55, 5947). Butyrate and crotonate have indistinguishable properties regarding negative modulation of wt GLIC. (2) We identify a locus in the pre-ß5 strand (Loop Ω) whose mutation inverses the effect of the mono-carboxylate crotonate from negative to positive modulation of the allosteric transitions, suggesting an involvement of the pre-ß5 strand in coupling the extracellular orthotopic receptor to pore gating. (3) As an extension to the previously proposed "in series" mechanism, we suggest that a orthotopic/orthosteric site-vestibular site-Loop Ω-ß5-ß6 "sandwich"-Pro-Loop/Cys-Loop series may be an essential component of orthotopic/orthosteric compound-elicited gating control in this pentameric ligand-gated ion channel, on top of which compounds targeting the vestibular site may provide modulation.

Performance of 5-Strand Hamstring Autograft Anterior Cruciate Ligament Reconstruction in the STABILITY Study: A Subgroup Analysis.

BACKGROUND: Anterior cruciate ligament (ACL) reconstructions (ACLRs) with graft diameters <8mm have been shown to have higher revision rates. The 5-strand (5S) hamstring autograft configuration is a proposed option to increase graft diameter. PURPOSE: To investigate the differences in clinical outcomes between 4-strand (4S) and 5S hamstring autografts for ACLR in patients who underwent ACLR alone or concomitantly with a lateral extra-articular tenodesis (LET) procedure. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Data from the STABILITY study were analyzed to compare a subgroup of patients undergoing ACLR alone or with a concomitant LET procedure (ACLR + LET) with a minimum graft diameter of 8mm that had either a 4S or 5S hamstring autograft configuration. The primary outcome was clinical failure, a composite of rotatory laxity and/or graft failure. The secondary outcome measures consisted of 2 patient-reported outcome scores (PROs)-namely, the ACL Quality of Life Questionnaire (ACL-QoL) and the International Knee Documentation Committee (IKDC) score at 24 months postoperatively. RESULTS: Of the 618 patients randomized in the STABILITY study, 399 (228 male; 57%) fit the inclusion criteria for this study. Of these, 191 and 208 patients underwent 4S and 5S configurations of hamstring ACLR, respectively, with a minimum graft diameter of 8mm. Both groups had similar characteristics other than differences in anthropometric factors-namely, sex, height, and weight, and Beighton scores. The primary outcomes revealed no difference between the 2 groups in rotatory stability (odds ratio [OR], 1.19; 95% CI, 0.77-1.84; P = .42) or graft failure (OR, 1.13; 95% CI, 0.51-2.50; P = .76). There was no significant difference between the groups in Lachman (P = .46) and pivot-shift (P = .53) test results at 24 months postoperatively. The secondary outcomes revealed no differences in the ACL-QoL (P = .67) and IKDC (P = .83) scores between the 2 subgroups. CONCLUSION: At the 24-month follow-up, there were no significant differences in clinical failure rates and PROs in an analysis of patients with 4S and 5S hamstring autografts of ≥8mm diameter for ACLR or ACLR + LET. The 5S hamstring graft configuration is a viable option to produce larger-diameter ACL grafts.

Failure Rates of 5-Strand and 6-Strand vs Quadrupled Hamstring Autograft ACL Reconstruction: A Comparative Study of 413 Patients With a Minimum 2-Year Follow-up.

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) with hamstring autograft has gained popularity. However, an unpredictably small graft diameter has been a drawback of this technique. Smaller graft diameter has been associated with increased risk of revision, and increasing the number of strands has been reported as a successful technique to increase the graft diameter. PURPOSE: To compare failure rates of 5-strand (5HS) and 6-strand (6HS) hamstring autograft compared with conventional 4-strand (4HS) hamstring autograft. We describe the technique in detail, supplemented by photographs and illustrations, to provide a reproducible technique to avoid the variable and often insufficient 4HS graft diameter reported in the literature. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We retrospectively reviewed prospectively collected data of all primary hamstring autograft ACLRs performed at our institution with a minimum 2-year follow-up and 8.0-mm graft diameter. A total of 413 consecutive knees met the study inclusion and exclusion criteria. The study population was divided into 5HS and 6HS groups as well as a 4HS control group. The primary outcome was failure of ACLR, defined as persistent or recurrent instability and/or revision ACLR. RESULTS: The analysis included 224, 156, and 33 knees in the 5HS, 6HS, and 4HS groups, respectively. The overall ACLR failure rate in this study was 11 cases (8%): 5 cases for 5HS, 3 cases for 6HS, and 3 cases for 4HS. No statistically significant differences were found among groups (P = .06). The mean graft diameter was 9 mm, and the mean follow-up was 44.27 months. CONCLUSION: The 5HS and 6HS constructs have similar failure rates to the conventional 4HS construct of 8.0-mm diameter and are therefore safe and reliable to increase the diameter of relatively smaller hamstring autografts. We strongly recommend using this technique when the length of the tendons permits to avoid failures reportedly associated with inadequate graft size.

Five-Strand Hamstring Autografts for Anterior Cruciate Ligament Reconstruction: A Systematic Review.

BACKGROUND: Recent studies have described surgical techniques to increase the hamstring graft diameter for anterior cruciate ligament reconstruction (ACLR), particularly for 5-strand hamstring (5HS) autografts. PURPOSE: To review the literature examining the biomechanical and clinical outcomes of 5HS autografts for ACLR. STUDY DESIGN: Systematic review; Level of evidence, 3. METHODS: A systematic review using PRISMA (Preferred Reporting Items for Systematic Meta-Analyses) guidelines was performed by searching PubMed, Embase, and the Cochrane Library for studies reporting the biomechanical and clinical outcomes of 5HS autografts. All English-language literature published from 2012 to 2018 that reported the biomechanical properties of 5HS grafts and/or clinical outcomes after ACLR with 5HS autografts with a minimum 1-year follow-up was reviewed by 2 independent reviewers. Graft diameter, stiffness, displacement, strength, failure rates, anteroposterior knee laxity, and patient-reported outcome scores were collected. The study methodology was evaluated using the modified Coleman Methodology Score. RESULTS: Two biomechanical and 3 clinical studies (1 with level 2 evidence, 2 with level 3 evidence) were included. The biomechanical studies compared the results of fourteen 4-strand hamstring (4HS) and fourteen 5HS graft specimens for ACLR (ovine grafts, n = 12; cadaveric grafts, n = 16) and found no significant differences in ultimate load, stiffness, displacement, and stress relaxation (P > .05), likely attributed to insufficient incorporation of the fifth strand. The mean 5HS cadaveric graft diameter (8.2 mm) was significantly greater than that of 4HS grafts (6.8 mm) (P = .002), whereas the mean ovine graft diameters were not significantly different (4HS, 5.2 mm; 5HS, 5.3 mm) (P > .05). Two clinical studies compared the outcomes after ACLR of 53 patients with a 4HS autograft versus 62 patients with a 5HS autograft, while 1 clinical study reported the outcomes of 25 patients after ACLR with a 5HS autograft (mean age, 28.7 years; mean follow-up, 24.8 months). The overall mean diameter for 4HS and 5HS autografts was 8.4 and 9.1 mm, respectively. There was no significant difference in failure rates between 4HS and 5HS autografts (P = .82). None of the comparative studies reported significant differences in any clinical outcomes (P > .05 for all). CONCLUSION: The available literature on traditional 4HS and 5HS autografts for ACLR is limited. Of the available data, clinical and biomechanical studies suggest no difference in outcomes after ACLR with either graft construct. Additional research is needed to determine whether creating a 5HS graft is beneficial.

A 5-Strand Hamstring Autograft Achieves Outcomes Comparable to Those of a 4-Strand Hamstring Autograft With a Graft Diameter of 8 mm or More in Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Quadrupled (4-strand) hamstring tendon autografts are commonly used in anterior cruciate ligament (ACL) reconstruction, but there is significant variability in their diameter. The 5-strand hamstring autograft has been used as a means of increasing the graft diameter in patients with undersized hamstring grafts. PURPOSE: To report the outcomes of primary ACL reconstruction using 5-strand hamstring autografts in patients in whom the 4-strand configuration produced a graft diameter of <8 mm and to compare these outcomes with those of ACL reconstruction using 4-strand semitendinosus-gracilis autografts with a graft diameter of ≥8 mm. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: The primary study group comprised 25 patients who underwent ACL reconstruction using a 5-strand hamstring autograft. The comparison group comprised 20 patients who underwent ACL reconstruction using a 4-strand hamstring autograft with a graft diameter of ≥8 mm. Interference screw fixation was used at the tibial and femoral ends for both groups of patients. Subjective questionnaires, including the Knee injury and Osteoarthritis Outcome Score (KOOS), the Lysholm score, and the Physical Component Summary and Mental Component Summary of the Short Form-36 (SF-36), were administered preoperatively as well as at 1- and 2-year follow-up visits. RESULTS: There were no significant differences in the patient demographics and preoperative scores between the 2 groups. The mean graft diameter was 9.06 ± 0.60 mm in the 5-strand group and 8.13 ± 0.32 mm in the 4-strand group (P < .05). There was no statistically significant difference between groups on postoperative Lysholm, KOOS Pain, KOOS Symptoms, KOOS Activities of Daily Living, KOOS Sports, KOOS Quality of Life, and SF-36 Physical Component Summary scores. CONCLUSION: In primary ACL reconstruction, the 5-strand hamstring autograft achieves clinical outcomes that are comparable to those of the 4-strand hamstring autograft with a graft diameter of ≥8 mm. The 5-strand graft technique is therefore a useful means of increasing the graft diameter when faced with an undersized hamstring graft.

Collision of Trapped Topoisomerase 2 with Transcription and Replication: Generation and Repair of DNA Double-Strand Breaks with 5' Adducts.

Topoisomerase 2 (Top2) is an essential enzyme responsible for manipulating DNA topology during replication, transcription, chromosome organization and chromosome segregation. It acts by nicking both strands of DNA and then passes another DNA molecule through the break. The 5' end of each nick is covalently linked to the tyrosine in the active center of each of the two subunits of Top2 (Top2cc). In this configuration, the two sides of the nicked DNA are held together by the strong protein-protein interactions between the two subunits of Top2, allowing the nicks to be faithfully resealed in situ. Top2ccs are normally transient, but can be trapped by cancer drugs, such as etoposide, and subsequently processed into DSBs in cells. If not properly repaired, these DSBs would lead to genome instability and cell death. Here, I review the current understanding of the mechanisms by which DSBs are induced by etoposide, the unique features of such DSBs and how they are repaired. Implications for the improvement of cancer therapy will be discussed.