Nonanatomic femoral tunnel placement increases the risk of subsequent meniscal surgery after ACLR: Part II-Patients without recurrent ACL injury.

PURPOSE: The purpose of this study was to identify risk factors for subsequent meniscal surgery following anterior cruciate ligament (ACL) reconstruction (ACLR) in patients without recurrent ACL injury. METHODS: Patients aged ≥14 years who underwent primary ACLR with minimum 1-year follow-up and without recurrent ACL injury were retrospectively reviewed. Patient demographics and surgical data at the time of ACLR were collected. Postoperative radiographs were used to measure femoral and tibial tunnel position, and posterior tibial slope. Univariate and multivariate analyses were performed to identify risk factors for subsequent meniscal surgery. RESULTS: Of 629 ACLRs that fulfilled the inclusion criteria, subsequent meniscal surgery was performed in 65 [10.3%] patients. Multivariate analysis revealed that medial meniscal repair at the time of ACLR, younger age, anterior femoral tunnel position and distal femoral tunnel position were significantly associated with subsequent meniscal surgery (p < 0.001, p = 0.016, p = 0.015, p = 0.035, respectively). The frequency of femoral tunnel placement >10% outside of the literature-established anatomic position was significantly higher in those who underwent subsequent meniscal surgery compared to those who did not (38.3% vs. 20.3%, p = 0.006). Posterior tibial slope and ACL graft type were not significantly associated with subsequent meniscal surgery. CONCLUSION: Medial meniscal repair at the time of ACLR, younger age and nonanatomic femoral tunnel placement were risk factors for subsequent meniscal surgery in patients without recurrent ACL injury. Femoral tunnel placement <10% outside of the native anatomic position is important to reduce the risk of subsequent meniscal surgery. LEVEL OF EVIDENCE: Level IV.

Lateral extra-articular tenodesis may be more cost-effective than independent anterolateral ligament reconstruction: A systematic review and economic analysis.

IMPORTANCE: Anterolateral augmentation during primary anterior cruciate ligament (ACL) reconstruction (ACLR) may lower rates of ACL graft failure. However, differences in costs between two techniques, lateral extra-articular tenodesis (LET) and anterolateral ligament reconstruction (ALLR), are unclear. OBJECTIVE: To perform a systematic review and subsequent cost-effectiveness analysis comparing LET versus ALLR in the setting of primary ACLR. The hypothesis was that LET is more cost-effective than ALLR. EVIDENCE REVIEW: A systematic review was conducted on studies in which patients underwent primary ACLR with a concomitant LET or ALLR with minimum 24 months follow-up published between January 2013 and July 2023. Primary outcomes included ACL graft failure rates and Knee Injury and Osteoarthritis Outcome Survey-Quality of Life (KOOS-QoL) subscale scores, which were used to determine health utilities measured by quality-adjusted life years (QALYs) gained. A decision tree model with one-way and two-way sensitivity analyses compared the cost of primary ACLR with a concomitant LET, independent autograft ALLR, or independent allograft ALLR. Costs were estimated using a combination of QALYs, institution prices, literature references, and a survey sent to 49 internationally recognized high-volume knee surgeons. FINDINGS: A total of 2505 knees undergoing primary ACLR with concomitant LET (n=1162) or ALLR (n=1343) were identified from 22 studies. There were 77 total ACL graft failures with comparable failure rates between patients receiving LET versus ALLR (2.9% vs. 3.2%, P=0.690). The average QALYs gained was slightly higher for those who received LET (0.77) compared to ALLR (0.75). Survey results revealed a 5 minute longer median self-reported operative time for ALLR (20 â€‹min) than LET (15 â€‹min). The estimated costs for LET, autograft ALLR, and allograft ALLR were $1,015, $1,295, and $3,068, respectively. CONCLUSIONS AND RELEVANCE: Anterolateral augmentation during primary ACLR with LET is more cost-effective than independent autograft and allograft ALLR given the lower costs and comparable clinical outcomes. Surgeons may utilize this information when determining the optimal approach to anterolateral augmentation during primary ACLR, although differences in preferred technique and health care systems may influence operative efficiency and material costs. LEVEL OF EVIDENCE: Systematic review; Level of evidence, IV.

Mutations in Drosophila tRNA processing factors cause phenotypes similar to Pontocerebellar Hypoplasia.

Mature transfer (t)RNAs are generated by multiple RNA processing events, which can include the excision of intervening sequences. The tRNA splicing endonuclease (TSEN) complex is responsible for cleaving these intron-containing pre-tRNA transcripts. In humans, TSEN copurifies with CLP1, an RNA kinase. Despite extensive work on CLP1, its in vivo connection to tRNA splicing remains unclear. Interestingly, mutations in CLP1 or TSEN genes cause neurological diseases in humans that are collectively termed Pontocerebellar Hypoplasia (PCH). In mice, loss of Clp1 kinase activity results in premature death, microcephaly and progressive loss of motor function. To determine if similar phenotypes are observed in Drosophila, we characterized mutations in crowded-by-cid (cbc), the CLP1 ortholog, as well as in the fly ortholog of human TSEN54. Analyses of organismal viability, larval locomotion and brain size revealed that mutations in both cbc and Tsen54 phenocopy those in mammals in several details. In addition to an overall reduction in brain lobe size, we also found increased cell death in mutant larval brains. Ubiquitous or tissue-specific knockdown of cbc in neurons and muscles reduced viability and locomotor function. These findings indicate that we can successfully model PCH in a genetically-tractable invertebrate.

Molecular determinants of metazoan tricRNA biogenesis.

Mature tRNAs are generated by multiple post-transcriptional processing steps, which can include intron removal. Recently, we discovered a new class of circular non-coding RNAs in metazoans, called tRNA intronic circular (tric)RNAs. To investigate the mechanism of tricRNA biogenesis, we generated constructs that replace native introns of human and fruit fly tRNA genes with the Broccoli fluorescent RNA aptamer. Using these reporters, we identified cis-acting elements required for tricRNA formation in vivo. Disrupting a conserved base pair in the anticodon-intron helix dramatically reduces tricRNA levels. Although the integrity of this base pair is necessary for proper splicing, it is not sufficient. In contrast, strengthening weak bases in the helix also interferes with splicing and tricRNA production. Furthermore, we identified trans-acting factors important for tricRNA biogenesis, including several known tRNA processing enzymes such as the RtcB ligase and components of the TSEN endonuclease complex. Depletion of these factors inhibits Drosophila tRNA intron circularization. Notably, RtcB is missing from fungal genomes and these organisms normally produce linear tRNA introns. Here, we show that in the presence of ectopic RtcB, yeast lacking the tRNA ligase Rlg1/Trl1 are converted into producing tricRNAs. In summary, our work characterizes the major players in eukaryotic tricRNA biogenesis.