Impact of histopathological classification of non-functioning adenomas on long term outcomes: comparison of the 2004 and 2017 WHO classifications.

PURPOSE: Outcomes of patients with non-functioning pituitary adenomas categorized using the 2004 and 2017 WHO classification systems are understudied. We report outcomes from the University of Virginia of patients with non-functioning pituitary adenomas categorized using both systems. METHODS: We constructed a database from all 239 patients who underwent resection of a non-functioning pituitary adenoma between 2003 and 2015 and had at least 5 years of follow-up. Pathologic diagnosis was determined under both the 2004 and 2017 WHO classification systems. We compared the rates of recurrence and progression between subtypes using univariate and multivariate Cox regression analyses. RESULTS: Nearly 30% of the tumors in our database were classified as null cell adenomas under the 2004 classification system, whereas only 10% of the tumors were classified as null cell adenomas using the 2017 classification system. Most of these tumors were reclassified as either corticotroph or gonadotroph adenomas. Despite our relatively large cohort and average follow-up of nearly 9 years, we did not detect a significant difference in recurrence and progression between subtypes. CONCLUSIONS: The majority of null cell adenomas diagnosed under the 2004 WHO classification system are reclassified as gonadotroph or corticotroph adenomas under the 2017 WHO classification system. Rates of progression and recurrence between subtypes are not as different as previously believed at our institution and require a larger cohort to further investigate.

Genomic and molecular characterization of pituitary adenoma pathogenesis: review and translational opportunities.

OBJECTIVE: Innovations in genomics, epigenomics, and transcriptomics now lay the groundwork for therapeutic interventions against neoplastic disease. In the past 30 years, the molecular pathogenesis of pituitary adenomas has been characterized. This enhanced understanding of the biology of pituitary tumors has potential to impact current treatment paradigms, and there exists significant translational potential for these results. In this review the authors summarize the results of genomics and molecular biology investigations into pituitary adenoma pathogenesis and behavior and discuss opportunities to translate basic science findings into clinical benefit. METHODS: The authors searched the PubMed and MEDLINE databases by using combinations of the keywords "pituitary adenoma," "genomics," "pathogenesis," and "epigenomics." From the initial search, additional articles were individually evaluated and selected. RESULTS: Pituitary adenoma growth is primarily driven by unrestrained cell cycle progression, deregulation of growth and proliferation pathways, and abnormal epigenetic regulation of gene expression. These pathways may be amenable to therapeutic intervention. A significant number of studies have attempted to establish links between gene mutations and tumor progression, but a thorough mechanistic understanding remains elusive. CONCLUSIONS: Although not currently a prominent aspect in the clinical management of pituitary adenomas, genomics and epigenomic studies may become essential in refining patient care and developing novel pharmacological agents. Future basic science investigations should aim at elucidating mechanistic understandings unique to each pituitary adenoma subtype, which will facilitate rational drug design.

Enhanced recovery after surgery in intramedullary and extramedullary spinal cord lesions: perioperative considerations and recommendations.

Enhanced recovery after surgery (ERAS) is an evidence-based approach developed to ameliorate the patient recovery process following surgical procedures. Employing a multimodal, multidisciplinary approach, ERAS implements strategies and treatment paradigms that have been shown to improve patient outcomes, reduce hospital length of stay, and ultimately reduce healthcare costs. With a substantial body of the literature supporting the implementation of ERAS in other surgical specialties, ERAS has only recently made its foray into spine surgery. Despite this, current studies are limited to spinal deformity and degenerative disease, with limited data regarding spinal cord surgery. This is due in part to the complex nature and rarity of spinal cord lesions, making the establishment of a formal ERAS protocol difficult. In developing an ERAS protocol, there must be a consensus on what factors are important to consider and implement. To address this, we reviewed the most recent advances in intramedullary and extramedullary spinal cord surgery in order to identify elements that influence patient outcomes. Using this information, the authors provide evidence-based recommendations with the intent of introducing a framework for future ERAS protocols with respect to treating spinal cord lesions.

Characteristics of traumatic brain injury during Operation Enduring Freedom-Afghanistan: a retrospective case series.

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality, especially among members of the armed services. Injuries sustained in the battlefield are subject to different mechanisms than those sustained in civilian life, particularly blast and high-velocity injury. Due to the unique nature of these injuries and the challenges associated with battlefield medicine, surgical interventions play a key role in acute management of TBI. However, the burden of chronic disease posed by TBI is poorly understood and difficult to investigate, especially in the military setting. The authors report the case logs of a United States Navy neurosurgeon, detailing the acute management and outcomes of 156 patients sustaining TBI between November 2010 and May 2011 during the war in Afghanistan. By demographics, more than half of the patients treated were local nationals. By mechanism of injury, blunt trauma (40.4%) and explosive injury (37.2%) were the most common contributors to TBI. Decompressive craniectomies (24.0%) and clot evacuations (14.7%) were the procedures most commonly performed. Nearly one-quarter of patients were transferred to receive further care, yet only 3 patients were referred for rehabilitative services. Furthermore, the data suggest that patients sustaining comorbid injuries in addition to TBI may be predisposed to worse outcomes. Improvements in documentation of military patients may improve knowledge of TBI and further identify potential variables or treatments that may affect prognosis. The increased survivability from TBI also highlights the need for additional research expenditure in the field of neurorehabilitation specifically.

Enhanced recovery after spine surgery: a systematic review.

OBJECTIVEEnhanced recovery after surgery (ERAS) is a multidimensional approach to improving the care of surgical patients using subspecialty- and procedure-specific evidence-based protocols. The literature provides evidence of the benefits of ERAS implementation, which include expedited functional recovery, decreased postoperative morbidity, reduced costs, and improved subjective patient experience. Although extensively examined in other surgical areas, ERAS principles have been applied to spine surgery only in recent years. The authors examine studies investigating the application of ERAS programs to patients undergoing spine surgery.METHODSThe authors conducted a systematic review of the PubMed and MEDLINE databases up to November 20, 2018.RESULTSTwenty full-text articles were included in the qualitative analysis. The majority of studies were retrospective reviews of nonrandomized data sets or qualitative investigations lacking formal control groups; there was 1 protocol for a future randomized controlled trial. Most studies demonstrated reduced lengths of stay and no increase in rates of readmissions or complications after introduction of an ERAS pathway.CONCLUSIONSThese introductory studies demonstrate the potential of ERAS protocols, when applied to spine procedures, to reduce lengths of stay, accelerate return of function, minimize postoperative pain, and save costs.

Robotic Sacroiliac Fixation Technique for Triangular Titanium Implant in Adult Degenerative Scoliosis Surgery: 2-Dimensional Operative Video.

Corrective surgery remains a definitive treatment for adult spinal deformity, improving pain and disability. With these cases, instrumentation to the pelvis with iliac fixation is recommended. Whether iliac or S2-Alar-Iliac (S2AI) trajectories are used, sacroiliac joint pain and long-term sacroilitis can be common after long-fusion constructs.1-3 Sacroiliac fusion with triangular titanium implants during fusion can reduce back pain associated with sacroiliac joint degeneration,3 provides reduction in sacroiliac joint motion and stress when added to S2AI screws, and potentially enhances mechanical stability of fusion constructs.4 Here, we present a technique for placing triangular titanium sacroiliac implants (iFuse BedrockTM; SI-BONE Inc, Santa Clara, California) alongside S2AI screws using a robotic platform (Mazor X; Medtronic Sofamor Danek, Medtronic Inc, Dublin, Ireland). Navigated robotics allows reduction in human error with implant placement, and potentially decreased operative time/fluoroscopy.5-7 Key surgical steps include placement of K wires for S2AI and bilateral SI-implants, tapping, replacing SI-implant K wires with guide pins, placing S2AI screws, and finally placing the SI-implant. Final placement is verified with intraoperative fluoroscopy. The patient described is a 61-yr-old woman with worsening adult degenerative scoliosis, lower back pain, left leg radicular pain, and mild right leg pain who failed conservative treatment. Examination revealed diminished strength in both legs. Imaging was significant for moderate sigmoid scoliosis, discogenic disease, and osteoarthritis at all levels. She consented to undergo corrective surgery. Postoperatively, the patient experienced resolution of her leg weakness and pain. Imaging demonstrated appropriate positioning of hardware. Prospective studies on the efficacy of the SI-implant are underway.

Secreted Peptides for Diagnostic Trajectory Assessments in Brain Injury Rehabilitation.

BACKGROUND: Rehabilitation following traumatic brain injury (TBI) significantly improves outcomes; yet TBI heterogeneity raises the need for molecular evidence of brain recovery processes to better track patient progress, evaluate therapeutic efficacy, and provide prognostication. OBJECTIVE: Here, we assessed whether the trajectory of TBI-responsive peptides secreted into urine can produce a predictive model of functional recovery during TBI rehabilitation. METHODS: The multivariate urinary peptidome of 12 individuals with TBI was examined using quantitative peptidomics. Measures were assessed upon admission and discharge from inpatient rehabilitation. A combination of Pavlidis template matching and partial least-squares discriminant analysis was used to build models on Disability Rating Scale (DRS) and Functional Independence Measure (FIM) scores, with participants bifurcated into more or less functional improvement groups. RESULTS: The produced models exhibited high sensitivity and specificity with the area under the receiver operator curve being 0.99 for DRS- and 0.95 for FIM-based models using the top 20 discriminant peptides. Predictive ability for each model was assessed using robust leave-one-out cross-validation with Q2 statistics of 0.64 (P = .00012) and 0.62 (P = .011) for DRS- and FIM-based models, respectively, both with a high predictive accuracy of 0.875. Identified peptides that discriminated improved functional recovery reflected heightened neuroplasticity and synaptic refinement and diminished cell death and neuroinflammation, consistent with postacute TBI pathobiology. CONCLUSIONS: Produced models of urine-based peptide measures reflective of ongoing recovery pathobiology can inform on rehabilitation progress after TBI, warranting further study to assess refined stratification across a larger population and efficacy in assessing therapeutic interventions.

A retrospective qualitative report of symptoms and safety from transcranial focused ultrasound for neuromodulation in humans.

Low intensity transcranial focused ultrasound (LIFU) is a promising method of non-invasive neuromodulation that uses mechanical energy to affect neuronal excitability. LIFU confers high spatial resolution and adjustable focal lengths for precise neuromodulation of discrete regions in the human brain. Before the full potential of low intensity ultrasound for research and clinical application can be investigated, data on the safety of this technique is indicated. Here, we provide an evaluation of the safety of LIFU for human neuromodulation through participant report and neurological assessment with a comparison of symptomology to other forms of non-invasive brain stimulation. Participants (N = 120) that were enrolled in one of seven human ultrasound neuromodulation studies in one laboratory at the University of Minnesota (2015-2017) were queried to complete a follow-up Participant Report of Symptoms questionnaire assessing their self-reported experience and tolerance to participation in LIFU research (Isppa 11.56-17.12 W/cm2) and the perceived relation of symptoms to LIFU. A total of 64/120 participant (53%) responded to follow-up requests to complete the Participant Report of Symptoms questionnaire. None of the participants experienced serious adverse effects. From the post-hoc assessment of safety using the questionnaire, 7/64 reported mild to moderate symptoms, that were perceived as 'possibly' or 'probably' related to participation in LIFU experiments. These reports included neck pain, problems with attention, muscle twitches and anxiety. The most common unrelated symptoms included sleepiness and neck pain. There were initial transient reports of mild neck pain, scalp tingling and headache that were extinguished upon follow-up. No new symptoms were reported upon follow up out to 1 month. The profile and incidence of symptoms looks to be similar to other forms of non-invasive brain stimulation.