The Role of the Gut Microbiome in Orthopedic Surgery-a Narrative Review.

PURPOSE OF REVIEW: The importance of the gut microbiome has received increasing attention in recent years. New literature has revealed significant associations between gut health and various orthopedic disorders, as well as the potential for interventions targeting the gut microbiome to prevent disease and improve musculoskeletal outcomes. We provide a broad overview of available literature discussing the links between the gut microbiome and pathogenesis and management of orthopedic disorders. RECENT FINDINGS: Human and animal models have characterized the associations between gut microbiome dysregulation and diseases of the joints, spine, nerves, and muscle, as well as the physiology of bone formation and fracture healing. Interventions such as probiotic supplementation and fecal transplant have shown some promise in ameliorating the symptoms or slowing the progression of these disorders. We aim to aid discussions regarding optimization of patient outcomes in the field of orthopedic surgery by providing a narrative review of the available evidence-based literature involving gut microbiome dysregulation and its effects on orthopedic disease. In general, we believe that the gut microbiome is a viable target for interventions that can augment current management models and lead to significantly improved outcomes for patients under the care of orthopedic surgeons.

Survival and neurological outcomes after stereotactic biopsy of diffuse intrinsic pontine glioma: a systematic review.

OBJECTIVE: Diffuse intrinsic pontine gliomas (DIPGs) are aggressive and malignant tumors of the brainstem. Stereotactic biopsy can obtain molecular and genetic information for diagnostic and potentially therapeutic purposes. However, there is no consensus on the safety of biopsy or effect on survival. The authors aimed to characterize neurological risk associated with and the effect of stereotactic biopsy on survival among patients with DIPGs. METHODS: A systematic review was performed in accordance with PRISMA guidelines to identify all studies examining pediatric patients with DIPG who underwent stereotactic biopsy. The search strategy was deployed in PubMed, Embase, and Scopus. The quality of studies was assessed using the Grading of Recommendations, Assessment, Development and Evaluation system, and risk of bias was evaluated with the Cochrane Risk of Bias in Nonrandomized Studies-of Interventions tool. Bibliographic, demographic, clinical, and outcome data were extracted from studies meeting inclusion criteria. RESULTS: Of 2634 resultant articles, 13 were included, representing 192 patients undergoing biopsy. The weighted mean age at diagnosis was 7.5 years (range 0.5-17 years). There was an overall neurosurgical complication rate of 13.02% (25/192). The most common neurosurgical complication was cranial nerve palsy (4.2%, 8/192), of which cranial nerve VII was the most common (37.5%, 3/8). The second most common complication was perioperative hemorrhage (3.6%, 7/192), followed by hemiparesis (2.1%, 4/192), speech disorders (1.6%, 3/192) such as dysarthria and dysphasia, and movement disorders (1.0%, 2/192). Hydrocephalus was less commonly reported (0.5%, 1/192), and there were no complications relating to wound infection/dehiscence (0%, 0/192) or CSF leak (0%, 0/192). No mortality was specifically attributed to biopsy. Diagnostic yield of biopsy revealed a weighted mean of 97.4% (range 91%-100%). Of the studies reporting survival data, 37.6% (32/85) of patients died within the study follow-up period (range 2 weeks-48 months). The mean overall survival in patients undergoing biopsy was 9.73 months (SD 0.68, median 10 months, range 6-13 months). CONCLUSIONS: Children with DIPGs undergoing biopsy have mild to moderate rates of neurosurgical complications and no excessive morbidity. With reasonably acceptable surgical risk and high diagnostic yield, stereotactic biopsy of DIPGs can allow for characterization of patient-specific molecular and genetic features that may influence prognosis and the development of future therapeutic strategies.

Management of severe scoliosis in patients with Turner's syndrome: A case series.

Aims and objectives: The prevalence and treatment of severe scoliosis and other spinal anomalies in patients with Turner's syndrome (TS) is not well reported. This is the largest case series to date regarding the treatment course and outcomes of severely scoliotic TS patients. Methods: A retrospective chart review was performed to identify all patients with TS seen at a single center academic pediatric institution from 2007 to 2021. Of these, the presence of concomitant severe scoliosis or other spinal anomalies was determined, defined by a major coronal curve measuring 45° or greater. Demographic, clinical, surgical, and radiologic data was collected at both pre- and post-intervention time points. Results: A retrospective chart review identified 306 patients with TS. Of those, six were identified to have severe scoliosis or other severe spinal anomalies requiring fusion. All four posterior spinal fusion (PSF) patients demonstrated improvement of their spinal curvature. One patient who electively pursued only bracing demonstrated minimal improvement and surgery was subsequently recommended, but not pursued. One patient expired from a pre-existing heart condition prior to intervention. All postoperative complications resolved with no further complications. The only brace-related complication was an allergic rash related to the brace material. Conclusion: All four patients who underwent PSF demonstrated significant improvement of their spinal curvature with few post-surgical complications. None of the patients in the bracing cohort demonstrated stabilization of their spinal curvature. Therefore, these data corroborate with prior studies, suggesting that operative management consisting of spinal fusion with instrumentation provides optimal clinical outcomes, compared to bracing only.

Scoliosis and Kyphosis Prevalence in Turner Syndrome: A Retrospective Review at a Pediatric Tertiary Care Medical Center.

BACKGROUND: The prevalence of major coronal and sagittal spinal curves (scoliosis and kyphosis) in Turner syndrome (TS) is not well established due to limited reporting. The relationship between growth hormone (GH) therapy and its effect on TS spinal curve incidence is also not well established. METHODS: A retrospective chart review of 306 TS patients from 2007 to 2021 evaluated major coronal and sagittal spinal curves, progression of the curve, and treatment with GH. Statistical significance (defined as P <0.05) between curvature rates and curve progression was compared between GH-treated patients and non-GH-treated patients using a χ 2 or Fisher exact test when appropriate. RESULTS: Thirty-seven of 306 (12%) TS patients had a radiographically relevant spinal deformity. Twenty-seven of 37 (73%) had mild; 4 of 37 (11%) had moderate, and 6 of 37 (16%) had severe curves. Of those with severe, 4 underwent spinal fusion, 1 was treated with bracing, and 1 was braced before a cardiovascular-related death. Regarding GH use among TS patients, 190 of 306 (62%) used GH versus 116 of 306 (38%) who did not. Of those with a spinal curve, 24 of 37 (65%) used GH compared with 13 of 37 (35%) who did not. On univariate analysis, GH therapy was not a risk factor for the diagnosis of a major spinal curve, a more severe degree of the curve at the time of diagnosis, or spinal curve progression ( P >0.05 for all). CONCLUSIONS: This is the largest single institution retrospective review of a TS cohort known to the authors assessing spinal curve prevalence and relation to GH treatment and demonstrates a TS spinal curve rate of 12% (37/306). Four of six (11%) TS patients with a severe curve underwent corrective spine fusion. There was no relationship between the use of GH and the presence of a spinal curve or curve progression. Further study is warranted to determine risk factors for curve progression. LEVEL OF EVIDENCE: Level III. CLINICAL RELEVANCE: This retrospective case series serves to review and address the prevalence of spinal deformity in TS patients and whether GH impacts worsening deformity.

Recurrent pediatric infratentorial ependymomas: a systematic review and meta-analysis on outcomes and molecular classification.

OBJECTIVE: The aim of this study was to summarize the prognosis of recurrent infratentorial ependymomas based on treatment and molecular characterization. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the authors searched the PubMed, Scopus, Embase, and Ovid databases for studies on recurrent infratentorial ependymomas in patients younger than 25 years of age. Exclusion criteria included case series of fewer than 5 patients and studies that did not provide time-dependent survival data. RESULTS: The authors' database search yielded 482 unique articles, of which 18 were included in the final analysis. There were 479 recurrent infratentorial pediatric ependymomas reported; 53.4% were WHO grade II and 46.6% were WHO grade III tumors. The overall mortality for recurrent infratentorial pediatric ependymomas was 49.1% (226/460). The pooled mean survival was 30.2 months after recurrence (95% CI 22.4-38.0 months). Gross-total resection (GTR) was achieved in 243 (59.0%) patients at initial presentation. The mean survival postrecurrence for those who received initial GTR was 42.3 months (95% CI 35.7-47.6 months) versus 26.0 months (95% CI 9.6-44.6 months) for those who received subtotal resection (STR) (p = 0.032). There was no difference in the mean survival between patients who received GTR (49.3 months, 95% CI 32.3-66.3 months) versus those who received STR (41.4 months, 95% CI 11.6-71.2 months) for their recurrent tumor (p = 0.610). In the studies that included molecular classification data, there were 169 (83.3%) posterior fossa group A (PFA) tumors and 34 (16.7%) posterior fossa group B (PFB) tumors, with 28 tumors harboring a 1q gain. PFA tumors demonstrated worse mean postprogression patient survival (24.7 months, 95% CI 15.3-34.0 months) compared with PFB tumors (48.0 months, 95% CI 32.8-63.2 months) (p = 0.0073). The average postrecurrence survival for patients with 1q+ tumors was 14.7 months. CONCLUSIONS: The overall mortality rate for recurrent infratentorial ependymomas was found to be 49.1%, with a pooled mean survival of 30.2 months in the included sample population. More than 80% of recurrent infratentorial ependymomas were of the PFA molecular subtype, and both PFA tumors and those with 1q gain demonstrated worse prognosis after recurrence.

Defining Key Residues of the Swi1 Prion Domain in Prion Formation and Maintenance.

Prions are self-perpetuating, alternative protein conformations associated with neurological diseases and normal cellular functions. Saccharomyces cerevisiae contains many endogenous prions, providing a powerful system to study prionization. Previously, we demonstrated that Swi1, a component of the SWI/SNF chromatin-remodeling complex, can form the prion [SWI+]. A small region, Swi11-38, with a unique amino acid composition of low complexity, acts as a prion domain and supports [SWI+] propagation. Here, we further examine Swi11-38 through site-directed mutagenesis. We found that mutations of the two phenylalanine residues or the threonine tract inhibit Swi11-38 aggregation. In addition, mutating both phenylalanines can abolish de novo prion formation by Swi11-38, whereas mutating only one phenylalanine does not. Replacement of half of or the entire eight-threonine tract with alanines has the same effect, possibly disrupting a core region of Swi11-38 aggregates. We also show that Swi11-38 and its prion-fold-maintaining mutants form high-molecular-weight, SDS-resistant aggregates, whereas the double-phenylalanine mutants eliminate these protein species. These results indicate the necessity of the large hydrophobic residues and threonine tract in Swi11-38 in prionogenesis, possibly acting as important aggregable regions. Our findings thus highlight the importance of specific amino acid residues in the Swi1 prion domain in prion formation and maintenance.

A Novel and Practical Method of Performing Atrioventricular Nodal Ablation via a Superior Approach in Patients with Refractory Atrial Fibrillation Undergoing Cardiac Resynchronization Device Implantation.

Atrioventricular node (AVN) ablation is a strategy to manage patients with drug-refractory atrial fibrillation (AF) and heart failure in whom cardiac resynchronization therapy (CRT) device implantation has been prescribed. This study describes a practical method to perform these two procedures using the same surgical site. Twenty-seven patients were indicated for AVN ablation and concurrent CRT device implantation while presenting with AF and rapid ventricular response (RVR) refractory to medical therapy. After placement of the right and left ventricular leads, a third puncture was made in the axillary vein to obtain access to perform the ablation. After hand-injecting contrast media through a RAMP™ (Abbott Laboratories, Chicago, IL, USA) sheath positioned in the right atrial cavity, the anatomical area corresponding to the AVN was identified using fluoroscopy cine runs obtained in the right anterior oblique and left anterior oblique projections. The adequate site for ablation was confirmed by the bipolar recording of a His-bundle deflection at the tip of the ablation catheter. Radiofrequency energy was delivered to achieve complete heart block. Subsequently, device implant was completed. The method was successfully applied in 27 consecutive cases, achieving permanent complete heart block in all patients. The mean radiofrequency time to achieve heart block was 110 seconds ± 43 seconds. The average procedural time including AVN ablation and device implant was 87 minutes ± 21 minutes. The images obtained with the hand-injected contrast media provided adequate information to readily identify the anatomical area corresponding to the AVN with 100% accuracy. This study suggests that ablation of the AVN can be safely and effectively accomplished via a superior approach in patients undergoing a CRT device implant.