Postoperative Access and Compliance Following Medial Patellofemoral Ligament Reconstruction in Hispanic Adolescents Mirrors the Non-Hispanic Adolescent Population.

BACKGROUND: Disparity in surgical care of patellar instability patients has not been fully investigated in the adolescent Hispanic population. This demographic has been shown to have differences in their care, including a lower rate of surgical treatment for patellar instability. Socioeconomic factors have been cited as a factor that influences patient outcomes and its relationship with ethnicity in context of patellar instability has not been evaluated. METHODS: Review performed of patients <19 years of age who underwent MPFL reconstruction between September 2008 and December 2015. Demographics, patient median household income data, and clinical variables were collected. Generalized linear mixed model (GLMM) with subject as random effects factor was utilized to evaluate differences between ethnicity groups due to nonindependence of data. It was then expanded to incorporate interactions between ethnicity and income. RESULTS: Ninety-five patellar dislocation events met criteria in 85 adolescents (mean age: 15.5 y). Thirty-four (40%) adolescents identified as Hispanic. In univariate analysis no differences were found between Hispanic and non-Hispanic patients. The multivariate GLMM demonstrated a significant interaction between ethnicity and income. The Hispanic group in the >100% State median income category had the highest rate of postoperative clinic appointments attended ( P =0.019). The Hispanic group in the <100% State median income category had the lowest rate of physical therapy appointments attended ( P =0.044). No differences were observed for duration of follow-up ( P =0.57) or final Kujala score ( P =0.75). CONCLUSIONS: Hispanic ethnicity alone is not associated with inferior postoperative management after MPFL reconstruction in adolescents. However, when socioeconomic status is considered, Hispanic patients of lower-income backgrounds are found to have lower compliance with postoperative rehab recommendations. LEVEL OF EVIDENCE: Level III.

Paraspinal muscle gene expression across different aetiologies in individuals undergoing surgery for lumbar spine pathology.

PURPOSE: The purpose of this study was to understand potential baseline transcriptional expression differences in paraspinal skeletal muscle from patients with different underlying lumbar pathologies by comparing multifidus gene expression profiles across individuals with either disc herniation, facet arthropathy, or degenerative spondylolisthesis. METHODS: Multifidus biopsies were obtained from patients (n = 44) undergoing lumbar surgery for either disc herniation, facet arthropathy, or degenerative spondylolisthesis. Diagnostic categories were based on magnetic resonance images, radiology reports, and intraoperative reports. Gene expression for 42 genes was analysed using qPCR. A one-way analysis of variance was performed for each gene to determine differences in expression across diagnostic groups. Corrections for multiple comparisons across genes (Benjamini-Hochberg) and for between-group post hoc comparisons (Sidak) were applied. RESULTS: Adipogenic gene (ADIPOQ) expression was higher in the disc herniation group when compared to the facet arthropathy group (p = 0.032). Adipogenic gene (PPARD) expression was higher in the degenerative spondylolisthesis group when compared to the disc herniation group (p = 0.013), although absolute gene expression levels for all groups was low. Fibrogenic gene (COL3A1) had significantly higher expression in the disc herniation group and facet arthropathy group when compared to the degenerative spondylolisthesis group (p < 0.001 and p = 0.038, respectively). When adjusted for multiple comparisons, only COL3A1 remained significant (p = 0.012). CONCLUSION: Individuals with disc herniation and facet arthropathy demonstrate higher COL3A1 gene expression compared to those with degenerative spondylolisthesis. Future research is required to further understand the biological relevance of these transcriptional differences.

Paraspinal Muscle Health is Related to Fibrogenic, Adipogenic, and Myogenic Gene Expression in Patients with Lumbar Spine Pathology.

BACKGROUND: Lumbar spine pathology is a common feature of lower back and/or lower extremity pain and is associated with observable degenerative changes in the lumbar paraspinal muscles that are associated with poor clinical prognosis. Despite the commonly observed phenotype of muscle degeneration in this patient population, its underlying molecular mechanisms are not well understood. The aim of this study was to investigate the relationships between groups of genes within the atrophic, myogenic, fibrogenic, adipogenic, and inflammatory pathways and multifidus muscle health in individuals undergoing surgery for lumbar spine pathology. METHODS: Multifidus muscle biopsies were obtained from patients (n = 59) undergoing surgery for lumbar spine pathology to analyze 42 genes from relevant adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic gene pathways using quantitative polymerase chain reaction. Multifidus muscle morphology was examined preoperatively in these patients at the level and side of biopsy using T2-weighted magnetic resonance imaging to determine whole muscle compartment area, lean muscle area, fat cross-sectional areas, and proportion of fat within the muscle compartment. These measures were used to investigate the relationships between gene expression patterns and muscle size and quality. RESULTS: Relationships between gene expression and imaging revealed significant associations between decreased expression of adipogenic/metabolic gene (PPARD), increased expression of fibrogenic gene (COL3A1), and lower fat fraction on MRI (r = -0.346, p = 0.018, and r = 0.386, p = 0.047 respectively). Decreased expression of myogenic gene (mTOR) was related to greater lean muscle cross-sectional area (r = 0.388, p = 0.045). CONCLUSION: Fibrogenic and adipogenic/metabolic genes were related to pre-operative muscle quality, and myogenic genes were related to pre-operative muscle size. These findings provide insight into molecular pathways associated with muscle health in the presence of lumbar spine pathology, establishing a foundation for future research that addresses how these changes impact outcomes in this patient population.

Dmrt1 is necessary for male sexual development in zebrafish.

The dmrt1 (doublesex and mab-3 related transcription factor 1) gene is a key regulator of sex determination and/or gonadal sex differentiation across metazoan animals. This is unusual given that sex determination genes are typically not well conserved. The mechanisms by which zebrafish sex is determined have remained elusive due to the lack of sex chromosomes and the complex polygenic nature of sex determination in domesticated strains. To investigate the role of dmrt1 in zebrafish sex determination and gonad development, we isolated mutations disrupting this gene. We found that the majority of dmrt1 mutant fish develop as fertile females suggesting a complete male-to-female sex reversal in mutant animals that would have otherwise developed as males. A small percentage of mutant animals became males, but were sterile and displayed testicular dysgenesis. Therefore zebrafish dmrt1 functions in male sex determination and testis development. Mutant males had aberrant gonadal development at the onset of gonadal sex-differentiation, displaying reduced oocyte apoptosis followed by development of intersex gonads and failed testis morphogenesis and spermatogenesis. By contrast, female ovaries developed normally. We found that Dmrt1 is necessary for normal transcriptional regulation of the amh (anti-Müllerian hormone) and foxl2 (forkhead box L2) genes, which are thought to be important for male or female sexual development respectively. Interestingly, we identified one dmrt1 mutant allele that co-operates with a linked segregation distorter locus to generate an apparent XY sex determination mechanism. We conclude that dmrt1 is dispensable for ovary development but necessary for testis development in zebrafish, and that dmrt1 promotes male development by transcriptionally regulating male and female genes as has been described in other animals. Furthermore, the strong sex-ratio bias caused by dmrt1 reduction-of-function points to potential mechanisms through which sex chromosomes may evolve.

Paraspinal muscles in individuals undergoing surgery for lumbar spine pathology lack a myogenic response to an acute bout of resistance exercise.

Background: Lumbar spine pathology (LSP) is a common source of low back or leg pain, and paraspinal muscle in these patients demonstrates fatty and fibrotic infiltration, and cellular degeneration that do not reverse with exercise-based rehabilitation. However, it is unclear of this lack of response is due to insufficient exercise stimulus, or an inability to mount a growth response. The purpose of this study was to compare paraspinal muscle gene expression between individuals with LSP who do and do not undergo an acute bout of resistance exercise. Methods: Paraspinal muscle biopsies were obtained from 64 individuals with LSP undergoing spinal surgery. Eight participants performed an acute bout of machine-based lumbar extension resistance exercise preoperatively. Gene expression for 42 genes associated with adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic pathways was measured, and differential expression between exercised and non-exercised groups was evaluated for (a) the full cohort, and (b) an age, gender, acuity, and etiology matched sub-cohort. Principal components analyses were used to identify gene expression clustering across clinical phenotypes. Results: The exercised cohort demonstrated upregulation of inflammatory gene IL1B, inhibition of extracellular matrix components (increased MMP3&9, decreased TIMP1&3, COL1A1) and metabolic/adipogenic genes (FABP4, PPARD, WNT10B), and downregulation of myogenic (MYOD, ANKRD2B) and atrophic (FOXO3) genes compared to the non-exercised cohort, with similar patterns in the matched sub-analysis. There were no clinical phenotypes significantly associated with gene expression profiles. Conclusion: An acute bout of moderate-high intensity resistance exercise did not result in upregulation of myogenic genes in individuals with LSP. The response was characterized by mixed metabolic and fibrotic gene expression, upregulation of inflammation, and downregulation of myogenesis.

Transmetatarsal Amputation Results in Higher Frequency of Revision Surgery and Higher Ambulation Rates Than Below-Knee Amputation.

Background: Selecting the level of amputation for patients with severe foot pathology can be challenging. The surgeon is sometimes confronted with an option between transmetatarsal amputation (TMA) and below-knee amputation (BKA). Recent studies have suggested that minor foot amputations have high revision rates and need for higher level of amputation. This study sought to compare the revision rates, need for higher level of amputation, postoperative ambulatory rate, and the demographic factors between these 2 operations. Methods: We retrospectively reviewed the records of patients undergoing either BKA or TMA at a single academic institution during an 8-year period. Demographic characteristics and medical history were collected and included in a binary logistic regression model to evaluate for independent predictors of needing revision surgery or needing higher-level amputation. Secondary outcomes included ambulatory status and wound status at last follow-up. Results: There was a total of 367 patients who underwent either BKA (n=293) or TMA (n=74).On binary logistic regression, the only significant independent predictor of needing revision surgery was undergoing TMA (odds ratio [OR] 2.30, CI 1.199-4.146, P = .011). The presence of PAD trended toward significance (OR 2.12, CI 0.99-4.493, P = .051). Similarly, significant independent predictors of needing higher level amputation were undergoing TMA (OR 4.117, CI 1.9-8.9, P < .001) and presence of PAD (OR 4.85, CI 1.59-14.85, P = .006). More TMA patients were ambulatory (56.8%) on last follow-up compared with BKA patients (30.9%). Conclusion: Transmetatarsal amputation has a higher risk of reoperation and need for revision amputation compared with below-knee amputation. Transmetatarsal amputation has a higher chance of returning patients to independent ambulation. Patients with peripheral arterial disease are at a higher risk of revision surgery and higher-level amputation with both operations. Level of Evidence: Level III, retrospective case review.

Elective lumbar fusion in the United States: national trends in inpatient complications and cost from 2002-2014.

BACKGROUND: Elective fusions for degenerative spine disease have increased over the past two decades in the USA, with variability in complications and hospital costs. The additional service costs associated with adverse perioperative events remain unknown. Our objective is to improve understanding of trends in safety and cost of elective lumbar fusions on a national scale. METHODS: A weighted sample of 1,526,386 adults undergoing elective lumbar fusion for degenerative indications were identified in the National Inpatient Sample (NIS) years 2002-2014. Twelve categories of major complications by system, and patient/hospital variables, were evaluated as predictors of the overall reimbursed cost. Mean differences (B) and 95% confidence intervals [95% CI] are reported. Significance is assessed at P<0.001. RESULTS: Nineteen percent of patients experienced inpatient complication. After adjusting for inflation, the mean overall cost was $ 32,802±19,557. Costs increased with presence of each of the 12 categories of complications, and by number of levels fused. Rates of most frequent complications and their adjusted cost-of-care were acute postoperative anemia (11.2%, B=$ 1817 [$ 1722-1913], P<0.001), renal/urinary (1.9%, B=$ 510 [$ 288-732], P<0.001), pulmonary (1.8%, B=$ 6014 [$ 5785-6243], P<0.001) and gastrointestinal (1.8%, B=$ 3699 [$ 3490-3908, P<0.001). The costliest adverse events were infection (B=$ 15,882 [$ 15,424-16,339], P<0.001), thromboembolism (B=$ 8856 [$ 8400-9311], P<0.001), hematoma/seroma/vascular (B=$ 8050 [$ 7784-8316], P<0.001). CONCLUSIONS: The number of elective lumbar fusions for degenerative spine disease increased 276% in the USA from 2002-2014 with growing surgeon preference for lateral techniques, and an increasing proportion of combined anterior and posterior approaches. Overall complication rates decreased from 2002-2014, despite an older patient population. After adjusting for inflation, cost was relatively stable across years 2002-2014. Complications by system were associated with increased cost, underscoring the need to address sources of complications and optimize early postoperative recovery in order to reduce healthcare expenditure.

Hospital complications and costs of spinal arteriovenous malformations in the United States from 2002-2014.

BACKGROUND: Spinal arteriovenous malformations (AVMs) are rare disease entities with significant morbidity if untreated. Risk factors of complications, hospitalization and costs-of-care remain in need of characterization. METHODS: Using the National Inpatient Sample years 2002-2014, adult subjects with spinal AVMs who underwent either laminectomy with lesion excision or endovascular embolization were extracted using ICD-9-CM diagnostic code 747.82. Predictors of inpatient complications, hospital length of stay (HLOS), and discharge home were evaluated using multivariable regression. Cost was evaluated using inflation-adjusted healthcare cost [charge*(cost/charge ratio)]. Mean differences (B), odds ratios (OR) and 95% CIs are reported. Significance was assessed at P<0.001. RESULTS: In 2546 weighted admissions, age was 54.4±16.5-years (laminectomy: 70.0%, embolization: 30.0%). Fifteen percent suffered inpatient complications. Cost of hospitalization was $ 41216±38511 and was elevated for subjects with complications ($67571±2636, vs. no complications: $36562±723, P<0.001). Increased costs for categories of complications ranged from $ 16525 (renal/urinary) to $62246 (thromboembolism). In surgical subjects, complications were more costly ($ 69761±2896, vs. no complications: 36520±809, P<0.001). On multivariable analysis, major/extreme disease severity and major/extreme mortality risk were associated with increased complications and HLOS (P<0.001). Elective admissions had shorter HLOS (B=-4.3-days, [-4.8, -3.8], P<0.001) and higher odds of discharge home (OR=2.6 [2.1-3.2], P<0.001). Laminectomy (vs. embolization) was associated with complications (OR=2.6, 95% CI [1.7-3.8], P<0.001), HLOS (B=3.4-days [2.9-4.0], P<0.001), and decreased discharge home (OR=0.3 [0.2-0.4], P<0.001). CONCLUSIONS: In spinal AVMs, high disease severity, non-elective admissions, and surgery are associated with complications, HLOS, and discharge to a non-home facility. Costs are elevated in patients suffering complications. Future studies are warranted.

Invagination of elevated lip liner preventing reduction of dislocated total hip.

Instability is the most common indication for revision total hip arthroplasty in the United States. Elevated-rim acetabular liners were introduced to minimize the risk of posterior instability. We describe a patient with multiple total hip arthroplasty dislocations secondary to component subsidence leading to instability. As the patient initially refused revision of his femoral component, he was treated with an elevated-rim acetabular liner. When this too dislocated, the hip could not be reduced concentrically. During operative exposure for a stem revision, the lipped aspect of the liner was found to have folded into the acetabulum thus preventing concentric reduction of the head. We conclude that invagination of the elevated lip of a polyethylene liner should be considered when concentric reduction of a dislocated hip proves difficult.

Cerebrospinal Fluid Leaks and Pseudomeningocele after Posterior Fossa Surgery: Effect of an Autospray Dural Sealant.

Background Posterior fossa craniotomies can be complicated by cerebrospinal fluid (CSF) leaks, infection, meningitis, neurologic deficits, and intracranial hypotension caused by defective closure of the dura. Secondary dural closures such as pericranial graft, muscle graft, glue, sealants, or fat graft are used. However, there have been few studies examining the use of sealants with a polyethylene glycol and polyethylenimine component. Objective We studied the effect of one such sealant, Adherus® (HyperBranch Medical Technology, Durham, NC, USA), as an adjunct to secondary closure methods in the reduction of the use of abdominal fat grafting and lumbar puncture/drains. Methods We retrospectively reviewed the surgical records of all patients undergoing posterior fossa cranial surgery during a two-year period at a tertiary university affiliated medical center. Results Overall, data a total of 122 patients (62 in the no Adherus and 60 in the Adherus group) were collected. There was no statistically significant difference in the 30-day incisional CSF leak rate (4.1% vs. 6.5%; p=0.183), 30-day non-incisional CSF leak rate (11.3% vs. 5.0%; p=0.205), and 30-day pseudomeningocele rate (16.1% vs. 13.3%; p=0.663) in the no Adherus and Adherus groups, respectively. However, there was a significant reduction in the use of abdominal fat grafting (0% vs. 30.7%; p<0.001) and intraoperative CSF diversion techniques (58.1% vs. 23.3%; p<0.001). Every instance of the use of Adherus saved on average, $809.36. Conclusions A statistically significant reduction in the use of CSF shunting procedures during posterior fossa craniotomy/craniectomy was achieved after the introduction of Adherus with no increase in CSF leak rate.

Cervical fusion for degenerative disease: A comprehensive cost analysis of hospital complications in the United States from 2002 to 2014.

PURPOSE: Recent data suggest great variability in costs for surgical hospitalization for spinal surgery. However, the magnitude of expenditures attributable to complications is unknown. The purpose of this study is to describe cost of care associated with surgical and medical complications after cervical spine surgery. MATERIALS AND METHODS: A retrospective cohort study utilizing the National Inpatient Sample years 2002-2014 was conducted. A weighted sample of 901,508 adults undergoing elective cervical fusion for degenerative indications was extracted using diagnostic and procedure codes. Twelve categories of major complications were identified, and patient/hospital variables were evaluated as predictors of the overall reimbursed cost using multivariate regression. Mean differences (B) and 95% confidence intervals were reported. RESULTS: The mean age was 52.2 ± 11.4 years, with 5.2% of patients experiencing a complication. Mean overall increase in inflation-adjusted cost associated with complication was $16,435 ± 10,358, varying significantly by type of complication, surgical approach, and number of levels fused. The most common complications and their attributed costs were dysphagia (1.6%, B = $2624 [2476-2771], P < 0.001), pulmonary complications (1.0%, B = $9334 [9110-9558], P < 0.001), and device-related complications (0.9%, B = $3125 [2927-3324], P < 0.001). The costliest complications were infection (0.1%, B = $25359 [24723-25994], P < 0.001), thromboembolism (0.1%, B = $17480 [16808-18153], P < 0.001), and neurological complications (0.2%, B = $10098 [9629-10567], P < 0.001). CONCLUSIONS: Although complications are rare after elective cervical fusion, they are associated with dramatically increase costs of care as high as $25,359 in the setting of postoperative infection. Improved understanding of the economic magnitude of complications may help guide efforts in reducing health care spending and improving perioperative care.

Predictors of 30-Day Outcomes in Octogenarians with Traumatic C2 Fractures Undergoing Surgery.

BACKGROUND: Predictors of surgical outcomes following traumatic axis (C2) fractures in octogenarians remain undercharacterized. METHODS: Patients age ≥80 years undergoing cervical spine surgery following traumatic C2 fractures were extracted from the National Sample Program of the National Trauma Data Bank (2003-2012). Outcomes include overall inpatient complications, individual complications with an incidence >1%, hospital length of stay (HLOS), discharge disposition, and mortality. Demographics, comorbidities, and injury predictors were analyzed using multivariable regression. Odds ratios (OR), mean differences, and 95% confidence intervals (CIs) were calculated. Statistical significance was assessed at P < 0.05. RESULTS: The cohort of 442 patients was 48.6% male and had a mean age of 84.3 ± 2.7 years. The distribution of admissions was 42.3% to the hospital floor, 40.3% to the intensive care unit (ICU), 7.7% to telemetry, 2.0% to the operating room, and 7.7% to other/unknown. Mortality was 9.7%, mean HLOS was 13.1 ± 9.2 days, the rate of complications was 38.5%, and 81.5% of survivors were discharged to a nonhome facility. Injury severity was predictive of mortality and overall complications. History of bleeding disorder/coagulopathy predicted mortality (OR, 4.02; 95% CI, 1.07-15.05), overall complications (OR, 3.01; 95% CI, 1.09-8.32), cardiac arrest (OR, 8.19; 95% CI, 1.06-63.54), and renal complications (OR, 10.36; 95% CI, 2.13-50.38). History of congestive heart failure predicted mortality (OR, 3.10; 95% CI, 1.10-8.69). ICU admission (vs. floor) predicted overall complications (OR, 2.01; 95% CI, 1.23-3.27) and pneumonia (OR, 4.65; 95% CI, 1.91-11.30). Telemetry admission (vs. floor) predicted unplanned intubation (OR, 7.76; 95% CI, 1.24-48.49). CONCLUSIONS: In this cohort of octogenarians undergoing surgery for traumatic C2 fracture, injury severity and a history of bleeding disorder/coagulopathy were identified as risk factors for inpatient complications and mortality. Heightened surveillance should be considered for ICU and/or telemetry admissions for the development of complications. These findings warrant consideration by the clinician, patient, and family to inform clinical decisions and goals of care.

Apolipoprotein E Epsilon 4 Genotype, Mild Traumatic Brain Injury, and the Development of Chronic Traumatic Encephalopathy.

The annual incidence of mild traumatic brain injury (MTBI) is 3.8 million in the USA with 10⁻15% experiencing persistent morbidity beyond one year. Chronic traumatic encephalopathy (CTE), a neurodegenerative disease characterized by accumulation of hyperphosphorylated tau, can occur with repetitive MTBI. Risk factors for CTE are challenging to identify because injury mechanisms of MTBI are heterogeneous, clinical manifestations and management vary, and CTE is a postmortem diagnosis, making prospective studies difficult. There is growing interest in the genetic influence on head trauma and development of CTE. Apolipoprotein epsilon 4 (APOE-ε4) associates with many neurologic diseases, and consensus on the ε4 allele as a risk factor is lacking. This review investigates the influence of APOE-ε4 on MTBI and CTE. A comprehensive PubMed literature search (1966 to 12 June 2018) identified 24 unique reports on the topic (19 MTBI studies: 8 athletic, 5 military, 6 population-based; 5 CTE studies: 4 athletic and military, 1 leucotomy group). APOE-ε4 genotype is found to associate with outcomes in 4/8 athletic reports, 3/5 military reports, and 5/6 population-based reports following MTBI. Evidence on the association between APOE-ε4 and CTE from case series is equivocal. Refining modalities to aid CTE diagnosis in larger samples is needed in MTBI.