Characterization of Lumbar Lordosis: Influence of Age, Sex, Vertebral Body Wedging, and L4-S1.

STUDY DESIGN: Retrospective radiographic review. OBJECTIVE: The objectives of the study were to determine the contributions to lumbar lordosis (LL) through both the vertebrae and the intervertebral disc (IVD), and to investigate the relationships between lumbar sagittal spine measurements and age and gender. SUMMARY OF BACKGROUND DATA: A small body of literature exists on the relative contributions of vertebral body and IVD morphology to LL, the effects of L4-S1 on overall LL, and the relationships/correlations between lumbar sagittal spine measurements. METHODS: Patients who met the inclusion criteria were retrospectively evaluated. Measurements included LL, pelvic incidence (PI), and % contributions of vertebral body wedging/IVD wedging/L4-S1 to LL. Patients were separated into groups by age and sex, demographic data were collected, and statistical analysis was completed. RESULTS: LL decreased with age, although PI remained similar. Females demonstrated increased LL and vertebral body wedging % than males. Males demonstrated increased L4-S1% than females. Despite a decrease in LL with age, patients maintained L4-S1% and IVD wedging %. There was a significant negative relationship between PI and IVD wedging, PI and L4-S1%, and LL and L4-S1%. CONCLUSIONS: During aging, the lumbar spine loses LL linearly. This occurs in the IVD and vertebral bodies. Females have increased LL compared with males, because of an increase in vertebral body wedging and IVD/vertebral wedging cranial to L4. In patients with high PI or LL, increased LL occurs from cranial to L4 and from vertebral body wedging.

Triangular Osteosynthesis as a Treatment of Lumbopelvic Dissociation with Acute Cauda Equina Syndrome in an 11-Year-Old Patient.

This case offers a safe and effective method for treating lumbopelvic dissociation in a pediatric patient with cauda equina syndrome using a triangular osteosynthesis construct. After a high-speed accident, an 11-year-old girl was admitted to the hospital with bowel and bladder incontinence and bilateral lower extremity weakness. The orthopaedic trauma and spine teams elected for surgical treatment with a triangular osteosynthesis construct, a procedure usually reserved for adults. The surgery was uncomplicated, and the patient experienced complete resolution of her preoperative symptoms. She is doing well over 1-year postoperatively, with full neurologic recovery, maintained reduction, bony healing, and subsequent implant removal. To our knowledge, this is the youngest reported case of lumbopelvic dissociation treated in this manner and represents a viable treatment option.

Applications of Carbon Fiber Instrumentation in Spinal Oncology: Recent Innovations in Spinal Instrumentation and 2-Dimensional Illustrative Operative Video.

BACKGROUND: The management of spinal oncology necessitates a multimodal approach, with surgical intervention, radiation-based therapy, and postoperative advanced imaging. These systems must work well together to provide optimal patient outcomes. Traditional metallic spinal implants produce image artifacts and lead to radiation dose attenuation, which inhibit both disease monitoring and disease treatment, respectively. OBJECTIVE: To demonstrate the feasibility of an improved biomaterial implant that provides structural stability, while also allowing for disease monitoring and treatment in spinal oncology patients. METHODS: From February 2021 to September 2021, 3 patients with spinal oncologic deformity requiring resection and posterior spinal stabilization underwent fixation with polyether ether ketone-carbon fiber implants at a single academic institution. RESULTS: Patient ages ranged from 23 to 74 years (mean: 44.7 years). All patients underwent posterior spinal fixation using standard approaches. They each received polyether ether ketone-carbon fiber pedicle screw and rod implants, placed in standard fashion. There were no dural tears, postoperative wound infections, or other complications related to their treatment. Postoperative surveillance revealed gross total resection of the targeted tumor on postoperative radiographic imaging. CONCLUSION: Polyether ether ketone-carbon fiber implants are a safe and effective option for the treatment of thoracolumbar posterior spinal pathology. The utilization of this novel type of instrumentation in posterior spinal approaches may provide benefit to patients with spinal tumors over existing forms of posterior spinal instrumentation.

Distal Ventral Iliac Pathway for Spinopelvic Fixation: Technique Description and Case Series.

BACKGROUND: Pelvic fixation improves the stability of spinal instrumentation and can be used in high-grade degenerative disease, trauma, deformity, and destabilizing invasive pathologies, such as infection and tumor. Classic techniques for spinopelvic fixation include traditional iliac screws and S2-Alar-Iliac screws. We present a case series describing the distal ventral iliac pathway (DVIP) for spinopelvic fixation and discuss surgical indications and merits of this technique. We describe the use of the DVIP for spinopelvic fixation in the setting of degenerative and traumatic pathologies, compare this technique with existing approaches, and summarize literature to support this approach. METHODS: One hundred twenty-eight cases of DVIP screws were identified at 1 academic medical center, and 3 cases were chosen as representative examples for technique demonstration. RESULTS: Patient ages ranged from 19 to 81 (mean 62) years. Intraoperative and postoperative complications include 12 incidental durotomies, 3 suprafascial infections, and 2 compressive hematomas. There were 22 instances of hardware failure and 8 instances of pseudoarthrosis. Overall, 26 patients underwent revision surgery. Mean estimated blood loss, operative time, and time under fluoroscopy were 1959 mL, 386 minutes, and 3.19 minutes, respectively. CONCLUSIONS: The DVIP is both safe and effective as a treatment for patients with degenerative and traumatic lumbosacral pathology. Spinopelvic fixation provides improved soft tissue coverage and fewer hardware complications at minimum of 1 year follow up. This case series demonstrates a novel surgical technique for spinopelvic fixation in the setting of numerous spinal pathologies. LEVEL OF EVIDENCE: 4. CLINICAL RELEVANCE: This surgical technique is less technically challenging than current approaches, minimizes radiation exposure, and obviates the need for horizontal connector rods. In addition, in highly destabilizing pathologies, this technique also allows for multiple screw placement within the ilium, while maintaining the ability to connect to a single rod construct. This technique is safe, technically approachable, and broadly applicable to an array of spinopelvic pathologies.

A transpedicular approach to complex ventrally situated thoracic intradural extramedullary tumors: technique, indications, and multiinstitutional case series.

OBJECTIVE: Ventrally situated thoracic intradural extramedullary tumors are surgically challenging and difficult to access, and they may be complicated by extensive adhesions and calcifications. Selecting an approach for adequate ventral access is key to complete resection and optimization of outcomes. The authors present a case series of patients who underwent resection of ventral thoracic intradural extramedullary tumors and discuss indications and considerations for this technique. Additionally, they describe the use of a posterolateral transpedicular approach for resection of ventral thoracic intradural extramedullary tumors compared with other techniques, and they summarize the literature supporting its application. METHODS: From May 2017 to August 2020, 5 patients with ventral thoracic intradural extramedullary tumors underwent resection at one of the two academic institutions. RESULTS: Patient ages ranged from 47 to 75 (mean 63.4) years. All tumors were diagnosed as meningiomas or schwannomas by histological examination. Three of the 5 patients had evidence of partial or extensive tumor calcification. Four of the 5 patients underwent an initial posterolateral transpedicular approach for resection, with positive radiographic and clinical outcomes from surgery. One patient initially underwent an unsuccessful traditional direct posterior approach and required additional resection 2 years later after interval disease progression. There were no postoperative wound infections, CSF leaks, or other complications related to the transpedicular approach. CONCLUSIONS: Posterolateral transpedicular tumor resection is a safe technique for the treatment of complex ventrally situated thoracic intradural extramedullary tumors compared with the direct posterior approach. Anecdotally, this approach appears to be particularly beneficial in patients with calcified tumors.

Epigenetic Regulation of Claudin-1 in the Development of Ovarian Cancer Recurrence and Drug Resistance.

Over 21,000 women are diagnosed with ovarian cancer (OC) in the United States each year and over half that number succumb to this disease annually, often due to recurrent disease. A deeper understanding of the molecular events associated with recurrent disease is needed to identify potential targets. Using genome-scale DNA methylation and gene expression data for 16 matched primary-recurrent advanced stage serous epithelial OCs, we discovered that Claudin-1 (CLDN1), a tight junction protein, shows a stronger correlation between expression and methylation in recurrent versus primary OC at multiple CpG sites (R= -0.47 to -0.64 versus R= -0.32 to -0.57, respectively). An independent dataset showed that this correlation is stronger in tumors from short-term (<3y) survivors than in tumors from long-term (>7y) survivors (R= -0.41 to -0.46 versus R= 0.06 to -0.19, respectively). The presence of this inverse correlation in short-term survivors and recurrent tumors suggests an important role for this relationship and potential predictive value for disease prognosis. CLDN1 expression increased following pharmacologic inhibition of DNA methyltransferase activity (p< 0.001), thus validating the role of methylation in CLDN1 gene inhibition. CLDN1 knockdown enhanced chemosensitivity and suppressed cell proliferation, migration, and wound healing (p< 0.05). Stable CLDN1 knockdown in vivo resulted in reduced xenograft tumor growth but did not reach significance. Our results indicate that the relationship between CLDN1 methylation and expression plays an important role in OC aggressiveness and recurrence.

Normative Parameters of Gastrocnemius Muscle Stiffness and Associations with Patient Characteristics and Function.

BACKGROUND: Quantifying muscle stiffness may aid in the diagnosis and management of individuals with muscle pathology. Therefore, the primary purpose of this study was to establish normative parameters and variance estimates of muscle stiffness in the gastrocnemius muscle in a resting and contracted state. A secondary aim was to identify demographic, anthropometric, medical history factors, and biomechanical factors related to muscle stiffness. METHODS: Stiffness of the gastrocnemius muscle was measured in both a resting and contracted state in 102 asymptomatic individuals in this cross-sectional study. Differences based on muscle state (resting vs contracted) and sex (female vs male) were assessed using a 2 X 2 analysis of variance (ANOVA). Associations between muscle stiffness and sex, age, BMI, race, exercise frequency, exercise duration, force production, and step length were assessed using correlation analysis. RESULTS: Gastrocnemius muscle stiffness significantly increased from a resting to a contracted state [mean difference: 217.5 (95% CI: 191.3, 243.8), p < 0.001]. In addition, muscles stiffness was 35% greater for males than females in a resting state and 76% greater in a contracted state. Greater muscle stiffness in a relaxed and contracted state was associated with larger plantarflexion force production (r = .26, p < 0.01 and r = .23, p < 0.01 respectively). CONCLUSION: Identifying normative parameters and variance estimates of muscle stiffness in asymptomatic individuals may help guide diagnosing and managing individuals with aberrant muscle function. LEVEL OF EVIDENCE: 2b Individual Cohort Study. CLINICAL RELEVANCE: What is known about the subject: Muscle stiffness has been shown to be related to individuals with pathology such as Achilles tendinopathy; however, research is sparse regarding normative values of muscle stiffness. Measuring muscle stiffness may also be a way to potentially predict individuals prone to injury or to monitor the effectiveness of management strategies.What this study adds to existing knowledge: This study establishes defined estimates of muscle stiffness of the gastrocnemius in both a relaxed and contracted state in healthy individuals. Myotonometry measures of muscle stiffness demonstrated an increase in stiffness during contraction that varies by sex. Greater gastrocnemius muscle stiffness was associated with increased plantarflexion force production.

Targeting Dormant Ovarian Cancer Cells In Vitro and in an In Vivo Mouse Model of Platinum Resistance.

Spheroids exhibit drug resistance and slow proliferation, suggesting involvement in cancer recurrence. The protein kinase C inhibitor UCN-01 (7-hydroxystaurosporine) has shown higher efficacy against slow proliferating and/or quiescent ovarian cancer cells. In this study, tumorigenic potential was assessed using anchorage-independent growth assays and spheroid-forming capacity, which was determined with ovarian cancer cell lines as well as primary ovarian cancers. Of 12 cell lines with increased anchorage-independent growth, 8 formed spheroids under serum-free culture conditions. Spheroids showed reduced proliferation (P < 0.0001) and Ki-67 immunostaining (8% vs. 87%) relative to monolayer cells. Spheroid formation was associated with increased expression of mitochondrial pathway genes (P ≤ 0.001) from Affymetrix HT U133A gene expression data. UCN-01, a kinase inhibitor/mitochondrial uncoupler that has been shown to lead to Puma-induced mitochondrial apoptosis as well as ATP synthase inhibitor oligomycin, demonstrated effectiveness against spheroids, whereas spheroids were refractory to cisplatin and paclitaxel. By live in vivo imaging, ovarian cancer xenograft tumors were reduced after primary treatment with carboplatin. Continued treatment with carboplatin was accompanied by an increase in tumor signal, whereas there was little or no increase in tumor signal observed with subsequent treatment with UCN-01 or oltipraz. Taken together, our findings suggest that genes involved in mitochondrial function in spheroids may be an important therapeutic target in preventing disease recurrence.

Cannabinoid exposure and altered DNA methylation in rat and human sperm.

Little is known about the reproductive effects of paternal cannabis exposure. We evaluated associations between cannabis or tetrahydrocannabinol (THC) exposure and altered DNA methylation in sperm from humans and rats, respectively. DNA methylation, measured by reduced representation bisulfite sequencing, differed in the sperm of human users from non-users by at least 10% at 3,979 CpG sites. Pathway analyses indicated Hippo Signaling and Pathways in Cancer as enriched with altered genes (Bonferroni p < 0.02). These same two pathways were also enriched with genes having altered methylation in sperm from THC-exposed versus vehicle-exposed rats (p < 0.01). Data validity is supported by significant correlations between THC exposure levels in humans and methylation for 177 genes, and substantial overlap in THC target genes in rat sperm (this study) and genes previously reported as having altered methylation in the brain of rat offspring born to parents both exposed to THC during adolescence. In humans, cannabis use was also associated with significantly lower sperm concentration. Findings point to possible pre-conception paternal reproductive risks associated with cannabis use.

Genotype-Epigenotype Interaction at the IGF2 DMR.

Paternally expressed Insulin-like Growth Factor II (IGF2) encodes a gene whose protein product functions as a potent growth mitogen. Overexpression of IGF2 has been implicated in a wide number of disorders and diseases. IGF2 is regulated in part by differential methylation of the two parentally derived alleles. The differentially methylated region (DMR) located upstream of the imprinted promoters of IGF2 exhibits plasticity under environmental stress and is hypomethylated in several types of cancer. Through bisulfite pyrosequencing and confirmation by nucleotide sequencing, we discovered a CpG to CpC transversion that results in hypomethylation of one of the three CpGs comprising this DMR. The presence of the polymorphism introduces a genetic rather than an environmentally-driven epigenetic source of hypomethylation that is additive to non-genetic sources.

Family System Interventions for Families of Children with Autism Spectrum Disorder.

The increasing prevalence of autism spectrum disorder (ASD), the severity of impairment, and its impact on systems are a source of ever-growing concern. This article (1) describes briefly the spectrum of ASD and its treatments; (2) discusses the impact that ASD has on the individual, family, and external environment; and (3) discusses the application of family therapy principles in order to meet the needs of children and families affected by ASD. Illustrative case examples are presented.

Improving work outcomes of dysthymia (persistent depressive disorder) in an employed population.

OBJECTIVE: To test the effectiveness of a work-focused intervention (WFI) on the work outcomes of employed adults with dysthymia. METHOD: This subgroup analysis from a randomized controlled trial compares an initial sample of 167 employees (age: ≥45 years), screened for dysthymia using the PC-SAD without current major depressive disorder randomized to WFI (n=85) or usual care (UC) (n=82). Study sites included 19 employers and five additional organizations. Telephone-based WFI counseling (eight, twice monthly 50-min sessions) provided work coaching and modification, care coordination and cognitive behavioral therapy. Adjusted mixed effects models compared the WFI vs. UC group preintervention to 4-month postintervention change in at-work limitations measured by the Work Limitations Questionnaire. Secondary outcome analysis compared the change in self-reported absences and depression symptom severity (Patient Health Questionnaire PHQ-9 scores). RESULTS: Work productivity loss scores improved 43.0% in the WFI group vs. 4.8% in UC (difference in change: P<.001). Absence days declined by 58.3% in WFI vs. 0.0% in UC (difference in change: P=.09). Mean PHQ-9 depression symptom severity declined 44.2% in WFI vs. 5.3% in UC (difference in change: P<.001). CONCLUSION: At 4 months, the WFI was more effective than UC on two of the three outcomes. It could be an important mental and functional health improvement resource for the employed dysthymic population.

The reliability and validity of the Caregiver Work Limitations Questionnaire.

OBJECTIVE: To test a new Caregiver Work Limitations Questionnaire (WLQ). On the basis of the original WLQ, this new survey instrument assesses the effect of caregiving for ill and/or disabled persons on the caregiver's work performance. METHOD: A questionnaire was administered anonymously to employees of a large business services company. Scale reliability and validity were tested with psychometric methods. RESULTS: Of 4128 survey participants, 18.3% currently were caregivers, 10.2% were past caregivers, and 71.5% were not caregivers. Current caregivers were limited in their ability to perform basic job tasks between mean 10.3% and 16.8% of the time. Confirmatory factor analysis yielded a scale structure similar to the WLQ's. Scales reliabilities (the Cronbach's α) ranged from 0.91 to 0.95. CONCLUSIONS: The Caregiver WLQ is a new tool for understanding the workplace effect of caregiving.