Return to sports following discectomy: does a consensus exist?

INTRODUCTION: In the USA, lumbar discectomy is one of the most commonly performed spinal procedures. As certain sports are considered to be major risk factors for disc herniation, the question remains as to when highly active patients should return to their previous level of activity. This study aimed to analyze spine surgeons' opinions on when patients may return to activities following discectomy as well as their underlying rationale for their decision. METHODS: A questionnaire was designed by five different fellowship-trained spine surgeons for the 168 members of the Spine Society of Australia. Questions on the surgeons experience, decision making, preferred surgical technique, the postoperative rehabilitation and the response to patient expectations were included. RESULTS: In total, 83.9% of surgeons discuss the postoperative level of activity with their patients. Sport is considered as an important contributor for good functional outcome by 71.0% of surgeons. Surgeons recommend avoiding, often permanently, weightlifting (35.7%) of the time, rugby (21.4%), horseback riding (17.9%) as well as martial arts (14.3%) postoperatively even with previous training. The return to high levels of activity is considered as a major risk factor for disc herniation recurrence by 25.8% of surgeons. Return to high level of activity is typically recommended after 3 months by 48.4% of surgeons. CONCLUSION: So far no consensus on the rehabilitation protocol and return to level of activity exists. Recommendations depend on personal experience as well as the individuals' training, and typically, a period of avoidance of sport for up to 3 months is recommended. LEVEL OF EVIDENCE: Level III, therapeutic and prognostic study.

A Degron Blocking Strategy Towards Improved CRL4CRBN Recruiting PROTAC Selectivity.

Small molecules inducing protein degradation are important pharmacological tools to interrogate complex biology and are rapidly translating into clinical agents. However, to fully realise the potential of these molecules, selectivity remains a limiting challenge. Herein, we addressed the issue of selectivity in the design of CRL4CRBN recruiting PROteolysis TArgeting Chimeras (PROTACs). Thalidomide derivatives used to generate CRL4CRBN recruiting PROTACs have well described intrinsic monovalent degradation profiles by inducing the recruitment of neo-substrates, such as GSPT1, Ikaros and Aiolos. We leveraged structural insights from known CRL4CRBN neo-substrates to attenuate and indeed remove this monovalent degradation function in well-known CRL4CRBN molecular glues degraders, namely CC-885 and Pomalidomide. We then applied these design principles on a previously published BRD9 PROTAC (dBRD9-A) and generated an analogue with improved selectivity profile. Finally, we implemented a computational modelling pipeline to show that our degron blocking design does not impact PROTAC-induced ternary complex formation. We believe that the tools and principles presented in this work will be valuable to support the development of targeted protein degradation.

Spinal fractures in fused spines: nonoperative treatment is a reliable alternative.

INTRODUCTION: Spinal fractures in fused spines such as in ankylosing spondylitis or DISH are typically of type B or C fractures where operative treatment is recommended. The mortality rate in non-operatively treated patients is reported to be 51%. The purpose of this study was to investigate the mortality rate, complication rate and demographics of patients following non-operatively treatment in fused spine injuries. METHODS: Between 2019 and 2021, a retrospective study was conducted including all patients who presented to our trauma center with a spinal fracture of a fused spine. Radiology and patient charts were analyzed for fracture pattern, complications, neurological deficit, comorbidities, and mortality rate. RESULTS: A total of 49 patients were found at a mean age was 79.8 ± 10.9 years and primarily males were affected in 65.3%. All fractures were of type B and the thoracic spine was involved in 85.7%. The mean follow-up was 6.3 ± 8.2 months and fusion was obtained in all patients. No neurological deficit was observed in any. A total of 13 patients died at a mean age of 86.5 ± 10.0 years after 157.1 ± 158.1 days. 6 patients (10.2%) deceased within the first 6 weeks at a mean age of 91.8 ± 3.8 years. One patient each suffered from heart failure, an acute delirium, end stage colon cancer and subdural hemorrhage. CONCLUSION: This study shows that the mortality rate in the first 6 weeks following a fracture in a fused spine is 10.2% for patients above the age of 90 years. Therefore, non-operative treatment should be taken into consideration as the mortality rate in other studies may be overestimated. LEVEL OF EVIDENCE: III, retrospective study.

Percutaneous elevation of radial head fractures without fixation - a promising technique.

The aim of the study is to describe the surgical technique and to report the outcomes of triceps reflecting anconeus pedicle (TRAP) approach for intercondylar fractures of the humerus. Twenty two patients with intercondylar fractures of the humerus were operated on by open reduction via the TRAP approach and internal fixation with dual precontoured locking plates. Data were collected on union time, postoperative complications, range of motion (ROM), triceps power, and objective clinical measurement. All fractures were united with a mean union time of 16.5 weeks (range 12-22). All patients had good-to-excellent Mayo Elbow Performance (MEP) score results with a mean ROM of 118.2 degrees (range 90-135). Triceps power was grade 5 in 16 patients and grade 4 in 6. There were 3 transient ulnar nerve palsy and 1 heterotopic ossification. TRAP approach is safe and effective in terms of utility for articular reduction, restoration of elbow motion, and triceps function for intercondylar fractures of the humerus.

Hydroxylation of anilides by engineered cytochrome P450BM3.

Biocatalytic direct monohydroxylation of anilides has been achieved on preparative scale using mutant cytochrome P450BM3 enzymes. Representative mono- and disubstituted N-trifluoromethanesulfonyl anilides are shown to be converted in most cases to the corresponding 4-hydroxy derivatives, with substituent hydroxylation also occurring in two cases. By mutation variation, it is possible to achieve selective hydroxylation of either ring- or side-chain sites.

Synthesis of cyclic alkenylsiloxanes by semihydrogenation: a stereospecific route to (Z)-alkenyl polyenes.

Cyclic alkenylsiloxanes were synthesized by semihydrogenation of alkynylsilanes-a reaction previously plagued by poor stereoselectivity. The silanes, which can be synthesized on multigram scale, undergo Hiyama-Denmark coupling to give (Z)-alkenyl polyene motifs found in bioactive natural products. The ring size of the silane is crucial: five-membered cyclic siloxanes also couple under fluoride-free conditions, whilst their six-membered homologues do not, enabling orthogonality within this structural motif.

Two Total Syntheses of Trigoxyphins K and L.

Two total syntheses are presented for trigoxyphins K and L, tricyclic terpenoids from Trigonostemon xyphophylloides. The first proceeds via electrophlic cyclization in A/C-ring substrates to close the B ring at C4-C5 and then 1O2-mediated hydroxybutenolide formation to trigoxyphin L, with Luche reduction leading to trigoxyphin K. The second route develops from tetralone ring expansion to a B/C-ring intermediate that, by one-step O-demethylation-lactonization-isomerization, affords trigoxyphin K and then trigoxyphin L following enolate oxygenation.