The relevance of biologically effective dose for pain relief and sensory dysfunction after Gamma Knife radiosurgery for trigeminal neuralgia: an 871-patient multicenter study.

OBJECTIVE: Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure. METHODS: This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value. RESULTS: The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5-95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6-156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I-IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness. CONCLUSIONS: BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.

Association Between Hypercholesterolemia and Lumbar Degenerative Back Pain: A Medicare Expenditure Panel Survey (MEPS) Study.

Introduction Hypercholesterolemia is known to be a major contributor to the morbidity associated with cardiovascular disease and has been hypothesized to result in degenerative changes to the spine through atherosclerosis of segmental lumbar vessels. The purpose of this study is to determine the relationship between hypercholesterolemia and degenerative lumbar spine conditions in a U.S. cohort. Methods A total of 30,461 participated in the 2018 Medicare Expenditure Panel Survey (MEPS). Of those, 1,063 subjects responded to whether a diagnosis of lumbar disorders with low back pain was present. Odds ratios (OR) were calculated, and logistic regression analyses were adjusted for demographic, education, occupation, cardiovascular and mental health conditions. Results Of the 1,063 respondents, 455 (43%) reported back pain. Mean age of the respondents was 62.7±16.1. Men and women reported back pain at similar rates (43% vs 45%, p=0.664). Age, race, education level and occupation were similar between those with and without back pain (p>0.05). Those with a diagnosis of depression had higher odds of having back pain (p<0.05). Prevalence of back pain in subjects who responded to the back pain diagnosis item on the survey was 42.6%. On univariate analysis, diagnosis of total cholesterol levels was significantly higher in those with a diagnosis of back pain (OR 1.36, 95% CI [1.20-1.54], p<.0001). Multivariable analysis showed that hypercholesterolemia was independently associated with back pain (adjusted OR 1.32, 95% CI [1.04-1.68], p=0.021) after controlling for covariates. Conclusions In this study, subjects with hypercholesterolemia were 34% more likely to have back pain after controlling for confounders which presents as a recent discovery amongst U.S. populations. Further studies should be performed to investigate the management of hypercholesterolemia in the development and progression of degenerative lumbar back pain.

Factors Associated With the Rate of Recovery After Cervical Decompression Surgery for Degenerative Cervical Myelopathy: A Retrospective Analysis.

Introduction Degenerative cervical myelopathy (DCM) is a debilitating spinal condition with a wide variety of symptoms that can differ greatly among individuals. Common symptoms include numbness, extremity weakness, loss of balance, and gait instability. Decompression surgeries are commonly indicated for the treatment of DCM with varying outcomes reported in the literature. However, there is little evidence on the rate of recovery defined as the time until improvement in symptoms such as numbness, balance, and strength after surgery for DCM. The purpose of this study was to determine the rate of neurological recovery after surgery for DCM and its subsequent association with various risk factors to guide clinicians while providing care and improve patient education. Methods This study was a retrospective case series (n=180 patients) examining patients who underwent cervical decompression surgery for DCM. All patients had a clinical presentation of DCM, were diagnosed with DCM, had radiographic degenerative changes and cervical stenosis, and received surgical management from 2010 to 2020 in a tertiary hospital system. Data recorded included age, smoking status, duration of pre-operative symptoms, preoperative and postoperative pain, and postoperative rate of recovery (days until improvement) in numbness, upper extremity strength, and balance. Results Patients (n=180) had an average age of 65.7 years (SD ±9.2 years, range 43-93 years). The mean ± standard deviation for the rate of recovery (days until improvement) in numbness, upper extremity strength, and balance was 84.5 ± 94.4 days, 50.6 ± 42.8 days, and 60.4 ± 69.9 days, respectively. There was only a marginally significant association between the rate of recovery for numbness after surgery and patient age (p=0.053). The average rate of recovery in numbness for patients older than 60 years was significantly longer than those younger than 60 years (99.3 versus 60.2 days). Preoperative smoking status was significantly associated with persistent moderate to severe pain (p=0.032) within the six-month postoperative period. No significant correlations were seen between the rate of recovery for balance or strength and patient age or preoperative duration of symptoms. Conclusion There was great variability in the rate of recovery for postoperative symptoms after surgery for DCM. A longer time for improvement in postoperative numbness was only marginally correlated with the increased patient age after surgery for DCM. There was no correlation found between strength or balance recovery times and patient age. Smoking status was associated with moderate to severe postoperative pain after surgery for DCM. Furthermore, the duration of preoperative symptoms was not associated with improvement in postoperative symptoms after surgery for DCM. More research is needed to determine factors impacting the rate of recovery after surgery for DCM.

Aggressive thoracic vertebral hemangioma: case report and literature review.

INTRODUCTION: Vertebral hemangiomas are common and typically benign vascular lesions, with a prevalence of 10-12% in the general population and 2-3% in all spine tumors. A small subset of vertebral hemangiomas can be categorized as "aggressive" if they exhibit extraosseous expansion that compress the spinal cord, causing pain and various neurologic symptoms. This report details a case of aggressive thoracic hemangioma resulting in worsening pain and paraplegia to draw attention to this rare condition, including identification and treatment. CASE PRESENTATION: In this case, we present a 39 year-old female with a history of progressively worsening pain and paraplegia caused by compression of the spinal cord from an aggressive thoracic vertebral hemangioma. Clinical presentation, imaging, and biopsies, confirmed the diagnosis. A combined surgical and endovascular treatment strategy was implemented, and the patient's symptoms improved. DISCUSSION: Aggressive vertebral hemangioma is a rare condition that may cause symptoms that diminishes the quality of life, including pain and various neurological symptoms. Given the low number of such cases, and significant impact on lifestyle, it is beneficial to identify cases of aggressive thoracic hemangiomas to ensure timely and accurate diagnosis and help development of treatment guidelines. This case highlights the importance of identifying and diagnosing this rare but serious disease.

Percutaneous Rhizotomy of the Gasserian Ganglion in Patients With Mass Lesion-Associated Trigeminal Neuralgia: A Case Series.

BACKGROUND: Patients with trigeminal neuralgia (TN) secondary to mass lesions are typically treated by directly addressing the underlying pathology. In cases of TN not alleviated by treatment of the pathology, percutaneous balloon compression (PBC) and glycerol rhizotomy (Gly) are simple and effective ways to alleviate pain. However, there is limited literature on the use of these techniques for patients with TN caused by mass lesions. OBJECTIVE: To describe the use of PBC/Gly to treat mass lesion-related TN. METHODS: We report a retrospective, single-institution, descriptive case series of patients who presented with TN secondary to tumor or mass-like inflammatory lesion from 1999 to 2021. Patients with primary, idiopathic, or multiple sclerosis-related TN were excluded. Outcomes included Barrow Neurological Institute (BNI) pain intensity and hypesthesia scores, pain persistence, and postoperative complications. RESULTS: A total of 459 procedures were identified, of which 16 patients met the inclusion criterion (14 PBC and 2 Gly). Of the 15 patients with tumors, 12 had TN pain despite prior tumor-targeted radiation. Short-term (<3 months) BNI pain intensity improvement occurred in 15 (93.8%) patients. The mean follow-up was 54.4 months. Thirteen (81.3%) patients were pain-free (Barrow Neurological Institute pain intensity scale: IIIa-50%; I-25.0%; II-6.3%) for a mean of 23.8 (range 1-137) months. Ten patients (62.5%) had pain relief for ≥6 months from first procedure. New facial numbness developed immediately postprocedure in 8 (50%) patients. Transient, partial abducens nerve palsy occurred in 1 patient. CONCLUSION: PBC/Gly is an effective option for medically refractory TN in patients with mass-associated TN and is a viable option for repeat treatment.

Percutaneous vertebral augmentation for acute traumatic vertebral Fractures: A TQIP database study.

Patients with vertebral fractures may be treated with percutaneous vertebroplasty (VP) and kyphoplasty (KP) for pain relief. Few studies examine the use of VP and KP in the setting of an acute trauma. In this study, we describe the current use of VP/KP in patients with acute traumatic vertebral fractures. All patients in the ACS Trauma Quality Improvement Program (TQIP) 2016 National Trauma Databank with severe spine injury (spine AIS ≥ 3) met inclusion criteria, including patients who underwent PVA. Logistic regression was used to assess patient and hospital factors associated with PVA; odds ratios and 95 % confidence intervals are reported. 20,769 patients met inclusion criteria and 406 patients received PVA. Patients aged 50 or older were up to 6.73 (2.45 - 27.88) times more likely to receive PVA compared to younger age groups and women compared to men (1.55 [1.23-1.95]). Hospitals with a Level II trauma center and with 401-600 beds were more likely to perform PVA (2.07 [1.51-2.83]) and (1.82 [1.04-3.34]) respectively. African American patients (0.41 [0.19-0.77]), isolated trauma (0.64 [0.42-0.96]), neurosurgeon group size > 6 (0.47 [0.30-0.74]), orthopedic group size > 10, and hospitals in the Northeastern and Western regions of the U.S. (0.33 [0.21-0.51] and 0.46 [0.32-0.64]) were less likely to be associated with PVA. Vertebroplasty and kyphoplasty use for acute traumatic vertebral fractures significantly varied across major trauma centers in the United States by multiple patient, hospital, and surgeon demographics. Regional and institutional practice patterns play an important role in the use of these procedures.

Immediate Titanium Mesh Cranioplasty After Debridement and Craniectomy for Postcraniotomy Surgical Site Infections and Risk Factors for Reoperation.

BACKGROUND: We previously published a novel strategy for management of postcraniotomy bone flap infection consisting of single stage debridement, bone flap removal, and immediate titanium mesh cranioplasty. METHODS: Postcraniotomy patients with surgical site infections treated with surgical debridement, bone flap removal, and immediate titanium mesh cranioplasty were retrospectively reviewed. The primary outcome measure was reoperation due to persistent infection or wound healing complications from the titanium mesh. RESULTS: We included 48 patients, of which 15 (31.3%) were female. The most common primary diagnoses were glioblastoma (31.3%), meningioma (18.8%), and vascular/trauma (16.7%). Most patients had a history of same-site craniotomy prior to the surgery complicated by surgical site infection and 47.9% had prior cranial radiation. Thirty-six (75.0%) patients achieved resolution of their infection and did not require a second operation. Twelve (25.0%) patients required reoperation: 6 (12.5%) patients were found to have frank intraoperative purulence on reoperation, whereas 6 (12.5%) had reoperation for poor wound healing without any evidence of persistent infection. Cochran Armitage trend test revealed that patients with increasing number of wound healing risk factors had significantly higher risk of reoperation (P = 0.001). Prior intensity modulated radiotherapy alone was a significant risk factor for reoperation (6.5 [1.40-30.31], P = 0.002). Median follow-up time was 20.5 weeks. CONCLUSIONS: Immediate titanium mesh cranioplasty at the time of debridement and bone flap removal is an acceptable option in the management of post-craniotomy bone flap infection. Patients with multiple wound healing risk factors are at higher risk for reoperation.

A Single-Center Retrospective Analysis of Intracranial and Spinal Solitary Fibrous Tumor/Hemangiopericytoma Clinical Outcomes: Sex Association With Aggressiveness.

BACKGROUND: Solitary fibrous tumor/hemangiopericytoma (SFT/HPCT) is a rare tumor characterized by high recurrence rate and metastatic potential, even after surgical resection. We report on the clinical outcomes and risk factors for metastasis and progression-free survival (PFS) of patients diagnosed with SFT/HPCT. METHODS: We retrospectively identified patients with intracranial or spinal SFT/HPCT who underwent surgical resection and/or radiation therapy at our institution between 1995 and 2021. Baseline demographics, tumor characteristics, and outcome data were collected, and factors associated with PFS and metastasis were analyzed. RESULTS: Thirty-four subjects (mean age, 46.4 years; 44% female) with a histopathologically proven diagnosis of SFT/HPCT were included; the median follow-up was 89.7 months. Twenty-two tumors were supratentorial (67%), 6 (18%) were infratentorial, and 5 (15%) were spinal. Eleven patients had documented occurrence of metastasis (32%). Detailed preoperative and postoperative data were available for 25 patients (74%) who received treatment at our institution after their initial diagnosis. Of those, 20 (80%) underwent gross total resection (GTR), and 12 (48%) received either adjuvant or salvage radiotherapy. Univariate analyses revealed that males had a shorter mean PFS compared with females (25 months vs. 78 months; P = 0.01), and that patients who underwent GTR had a longer mean PFS compared with those who underwent subtotal resection (54 months vs. 23 months; P = 0.02). Male sex was the sole risk factor for metastasis (odds ratio, 6.75; 95% confidence interval, 1.19-38.02). CONCLUSIONS: Our data demonstrate a strong association between male sex and the outcomes of shorter PFS and higher risk for metastases. Further research is warranted to understand the clinical characteristics and outcomes of this rare tumor.

Association Between Hypercholesterolemia and Neck Pain in a Cross-sectional Population-based Study.

STUDY DESIGN: Retrospective cross-sectional analysis. SUMMARY OF BACKGROUND DATA: Degenerative changes are a major contributor to chronic neck pain. According to the vascular hypothesis of disk disease, atherosclerosis of the segmental arteries contributes to ischemia of the lumbar disks and resulting degenerative changes. Prior studies have demonstrated an association between atherosclerotic risk factors and lumbar degenerative disease. Similarly, atherosclerosis may contribute to cervical disk degeneration. Cardiovascular disease is associated with the development of atherosclerosis, particularly in small vessels to the cervical spine. Hypercholesterolemia is a major contributor to the morbidity associated with cardiovascular disease. This study aims to examine the relationship between hypercholesterolemia and neck pain. MATERIALS AND METHODS: Analysis was focused on the respondents to neck pain items of the standardized questionnaire. Odds ratios were calculated, and logistic regression analyses adjusted for demographic, education, and mental health conditions. RESULTS: There were 30,461 participants in the 2018 Medicare Expenditure Panel Survey (MEPS) survey. Of those, 1049 (3.4%) subjects responded to presence of a diagnosis of cervical disorders with neck pain. Mean age of respondents was 62.6±16.1. Overall prevalence of neck pain was 21.1%. Prevalence of neck pain was similar by age, sex, education level, and occupation ( P >0.05 for each). Neck pain was more prevalent in white race and lower total family income ( P <0.05). Current everyday smokers also had higher prevalence of neck pain ( P <0.05). Logistic regression analysis revealed a higher prevalence of neck pain in those with hypercholesterolemia after controlling for relevant covariates (adjusted odds ratio=1.54, 95% CI: 1.08-2.22, P =0.018). CONCLUSIONS: Subjects with hypercholesterolemia were 54% more likely to have neck pain after controlling for confounders. This suggests that hypercholesterolemia has a role to play in degeneration of the cervical spine. Therefore, prevention and proper management of high cholesterol may curtail the development and progression of degenerative cervical disk disease and thus, neck pain.

Parsonage Turner syndrome after cervical trauma and COVID-19 infection: a case report and review of the literature.

Background: Parsonage Turner syndrome is an uncommon condition characterized by acute onset shoulder pain, followed by neurologic deficits such as weakness and paresthesia. It is a condition that is thought to be immune-mediated, and triggered by several recognized factors such as trauma, surgery, infections, and immunizations. Upper extremity Parsonage Turner syndrome may affect any distribution of the brachial plexus and most commonly presents unilaterally. Clinical history and examination are the basis of diagnosis, although electrodiagnostic studies may be important for confirmation. Magnetic resonance and ultrasonographic studies have also been effectively used in the diagnosis of Parsonage Turner syndrome. The case herein presents a patient with multiple possible triggers of Parsonage Turner syndrome. Case Description: We present a case of 62-year-old Caucasian male with bilateral radicular pain and weakness in the upper extremities after cervical spine surgery for a fracture in a patient that was infected with COVID-19. The patient underwent electrodiagnostic testing, as well as ultrasonographic studies that demonstrated Parsonage Turner syndrome. A literature review on Parsonage Turner syndrome associated with trauma, surgery and COVID-19 was also performed. Conclusions: Most cases of Parsonage Turner syndrome have a known associated risk factor. The patient in this report is unique in that they had several known risk factors for Parsonage Turner syndrome simultaneously. For timely and accurate diagnosis, it is important to consider the potential triggers of Parsonage Turner syndrome including trauma, surgery and viral illnesses such as COVID-19.

Outcomes in surgical treatment for tandem spinal stenosis: systematic literature review.

BACKGROUND CONTEXT: Tandem spinal stenosis (TSS) refers to a narrowing of the spinal canal in distinct, noncontiguous regions. TSS most commonly occurs in the cervical and lumbar regions. Decompressive surgery is indicated for those with cervical myelopathy or persistent symptoms from lumbar stenosis despite conservative management. Surgical management typically involves staged procedures, with cervical decompression taking precedence in most cases, followed by lumbar decompression at a later time. However, several studies have shown favorable outcomes in simultaneous decompression. PURPOSE: The aim of this study is to provide a literature review and compare surgical outcomes in patients undergoing staged vs simultaneous surgery for TSS. STUDY DESIGN/SETTING: Systematic literature review. METHODS: A systematic review using PRISMA guidelines to identify original research articles for tandem spinal stenosis. PubMed, Cochrane, Ovid, Scopus, and Web of Science were used for electronic literature search. Original articles from 2005 to 2021 with more than eight adult patients treated surgically for cervical and lumbar TSS in staged or simultaneous procedures were included. Articles including pediatric patients, primarily thoracic stenosis, stenosis secondary to neoplasm or infectious disease, minimally invasive surgery, and non-English language were excluded. Demographic, perioperative, complications, functional outcome, and neurologic outcome data including mJOA (modified Japanese Orthopaedic Association), Nurick grade (NG), and ODI (Oswestry disability index), were extracted and summarized. RESULTS: A total of 667 articles were initially identified. After preliminary screening, 21 articles underwent full-text screening. Ten articles met our inclusion criteria. A total of 831 patients were included, 571 (68%) of them underwent staged procedures, and 260 (32%) underwent simultaneous procedures for TSS. Mean follow-ups ranged from 12 to 85 months. There was no difference in estimated blood loss (EBL) between staged and simultaneous groups (p=.639). Simultaneous surgeries had shorter surgical time than staged surgeries (p<.001). Mean changes in mJOA, NG, and ODI was comparable between staged and simultaneous groups. Complications were similar between the groups. There were more major complications reported in simultaneous operations, although this was not statistically significant (p=.301). CONCLUSION: Staged and simultaneous surgery for TSS have comparable perioperative, functional, and neurologic outcomes, as well as complication rates. Careful selection of candidates for simultaneous surgery may reduce the length of stay and consolidate rehabilitation, thereby reducing hospital-associated costs.

Failure of Conservatively Managed Traumatic Vertebral Compression Fractures: A Systematic Review.

BACKGROUND: Most vertebral compression fractures (VCFs) are successfully managed conservatively; however, some patients fail conservative management and require further surgical treatment. We sought to identify significant variables that contribute to progressive vertebral collapse in nonoperative treatment of traumatic VCFs. METHODS: A systematic review identified original research articles of conservatively managed VCFs secondary to trauma from inception to September 2021. Articles with patients treated with initial nonoperative therapy, AO type A0, A1, and A2 fractures, risk factor analysis, >10 patients, and vertebral fracture secondary to trauma were included. Articles with pediatric patients, burst fractures or AO type A3 and A4 fractures, vertebral fractures secondary to neoplasm or infectious disease, and operative versus nonoperative treatment comparations were excluded. Failure of nonoperative treatment was defined as salvage surgery/vertebral augmentation, progressive kyphosis, chronic pain, or functional disability. RESULTS: Of 3877 articles identified, 6 articles were included with 582 patients with conservatively managed thoracolumbar VCFs. Treatment failure was reported in 102 (17.5%) patients. Of 102 treatment failures, 37 (36.3%) were due to subsequent VCF, 33 (32.4%) were due to back pain or functional disability at follow-up, and 32 (31.4%) were due to increased compression rate or kyphotic deformity at follow-up. Prior VCF was a significant variable in 2 (33.3%) of 6 studies. Age, lumbar bone mineral density, segmental Cobb angle, and vertebral height loss were each described as a significant factor in 1 (16.7%) of the 6 studies. CONCLUSIONS: Identifying patients who are at risk for treatment failure may help select patients who would benefit from close clinical follow-up or early surgical/procedural intervention.

A comparison of robotic and laparoscopic minimally invasive adrenalectomy for adrenal malignancies.

BACKGROUND: Although guidelines recommend open adrenalectomy for most resectable adrenal malignancies, minimally invasive adrenalectomies are performed. Robotic adrenalectomies have become more popular recently, but there is a paucity of literature comparing laparoscopic and robotic resections. METHODS: Patients who underwent a planned minimally invasive adrenalectomy for adrenal malignancies (adrenocortical carcinoma, malignant pheochromocytoma, other carcinoma) were identified in the National Cancer Database. The primary outcome was the conversion rate from minimally invasive to open. Other post-operative outcomes and survival were compared. RESULTS: 416 patients (76.5%) underwent a laparoscopic adrenalectomy and 128 (23.5%) underwent a robotic operation. Demographics and clinical characteristics were similar. Approximately 19% of tumors resected by a minimally invasive approach were > 10 cm. The intra-operative conversion rate was decreased among robotic adrenalectomies relative to laparoscopic on univariate (7.8% vs. 18.3%, p = 0.005) and multivariable (odds ratio 0.39, p = 0.01) analyses. Using marginal standardization, there was a stepwise increase in the conversion rate as tumor size increased (< 5, 5-10, > 10 cm) for laparoscopic (7.5%, 18.0%, 33.2%) and robotic (3.1%, 8.3%, 17.3%) adrenalectomies. Operations which required conversion had a greater margin positivity rate, greater length of stay, and an association with poor overall survival. CONCLUSION: In contrast to most clinical guidelines, minimally invasive adrenalectomies are being performed on large malignant tumors. A laparoscopic approach was associated with a greater conversion rate and subsequent poor outcomes. If a surgeon is not planning an open adrenalectomy, but adrenal malignancy is a possibility, robotic adrenalectomy may be the preferred approach for resectable adrenal tumors.

Defining Common Features in High Impact and Highly Cited Journal Articles on Pancreatic Tumors: An Analysis of 1044 Studies Over the Past Decade.

INTRODUCTION: Surgical researchers seek to publish their findings in esteemed surgical journals to advance science and their careers. A detailed investigation of study and manuscript attributes in a specific research area, like pancreatic neoplasia, may yield informative insights for researchers looking to maximize research impact. OBJECTIVES: We analyzed publications related to pancreatic surgery primarily focused on pancreatic and periampullary tumors to identify elements associated with acceptance into high impact journals and a high likelihood of future citations. METHODS: A comprehensive review of nine surgical journals was performed between 2010 and 2019. Journals were grouped based on impact factor into high (>3), medium (1-3), and low (<1) impact categories. Each publication was annotated to identify study topic, methodology, and statistical approach. Findings were compared according to journal impact and number of citations to identify predictors of success across these 2 domains. RESULTS: A total of 1044 out of 21,536 (4.8%) articles published in the index journals were related to pancreatic tumors. The most common focus of study was perioperative outcomes and complications (46.7%). There was significantly more number of authors, participating institutions, countries, and randomized clinical trials in higher impact journals as well as high-cited articles (P < 0.05). Although advanced statistical analysis was used more commonly in high-impact journals (P < 0.05), it did not translate to higher citations (P > 0.05). CONCLUSIONS: Pancreatic neoplasia continues to be extensively studied in surgical literature. Specific elements of study methodology and design were identified as potentially key attributes to acceptance in high impact journals and citation success.

Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor.

The fish-hunting marine cone snail Conus geographus uses a specialized venom insulin to induce hypoglycemic shock in its prey. We recently showed that this venom insulin, Con-Ins G1, has unique characteristics relevant to the design of new insulin therapeutics. Here, we show that fish-hunting cone snails provide a rich source of minimized ligands of the vertebrate insulin receptor. Insulins from C. geographus, Conus tulipa and Conus kinoshitai exhibit diverse sequences, yet all bind to and activate the human insulin receptor. Molecular dynamics reveal unique modes of action that are distinct from any other insulins known in nature. When tested in zebrafish and mice, venom insulins significantly lower blood glucose in the streptozotocin-induced model of diabetes. Our findings suggest that cone snails have evolved diverse strategies to activate the vertebrate insulin receptor and provide unique insight into the design of novel drugs for the treatment of diabetes.

Insulin is a hormone critical for maintaining healthy blood sugar levels in humans. When the insulin system becomes faulty, blood sugar levels become too high, which can lead to diabetes. At the moment, the only effective treatment for one of the major types of diabetes are daily insulin injections. However, designing fast-acting insulin drugs has remained a challenge. Insulin molecules form clusters (so-called hexamers) that first have to dissolve in the body to activate the insulin receptor, which plays a key role in regulating the blood sugar levels throughout the body. This can take time and can therefore delay the blood-sugar control. In 2015, researchers discovered that the fish-hunting cone snail Conus geographus uses a specific type of insulin to capture its prey ­ fish. The cone snail releases insulin into the surrounding water and then engulfs its victim with its mouth. This induces dangerously low blood sugar levels in the fish and so makes them an easy target. Unlike the human version, the snail insulin does not cluster, and despite structural differences, can bind to the human insulin receptor. Now, Ahorukomeye, Disotuar et al. ­ including some of the authors involved in the previous study ­ wanted to find out whether other fish-hunting cone snails also make insulins and if they differed from the one previously discovered in C. geographus. The insulin molecules were extracted and analyzed, and the results showed that the three cone snail species had different versions of insulin ­ but none of them formed clusters. Ahorukomeye, Disotuar et al. further revealed that the snail insulins could bind to the human insulin receptors and could also reverse high blood sugar levels in fish and mouse models of the disease. This research may help guide future studies looking into developing fast-acting insulin drugs for diabetic patients. A next step will be to fully understand how snail insulins can be active at the human receptor without forming clusters. Cone snails solved this problem millions of years ago and by understanding how they have done this, researchers are hoping to redesign current diabetic therapeutics. Since the snail insulins do not form clusters and should act faster than currently available insulin drugs, they may lead to better or new diabetes treatments.

Combination of the low anticoagulant heparin CX-01 with chemotherapy for the treatment of acute myeloid leukemia.

Relapses in acute myelogenous leukemia (AML) are a result of quiescent leukemic stem cells (LSCs) in marrow stromal niches, where they resist chemotherapy. LSCs employ CXCL12/CXCR4 to home toward protective marrow niches. Heparin disrupts CXCL12-mediated sequestration of cells in the marrow. CX-01 is a low-anticoagulant heparin derivative. In this pilot study, we combined CX-01 with chemotherapy for the treatment of AML. Induction consisted of cytarabine and idarubicin (7 + 3) with CX-01. Twelve patients were enrolled (median age, 56 years; 3 women). Three, 5, and 4 patients had good-, intermediate-, and poor-risk disease, respectively. Day 14 bone marrows were available on 11 patients and were aplastic in all without detectable leukemia. Eleven patients (92%) had morphologic complete remission after 1 induction (CR1). Eight patients were alive at a median follow-up of 24 months (4 patients in CR1). Three patients received an allogeneic stem cell transplant in CR1. Median disease-free survival was 14.8 months. Median overall survival was not attained at the maximum follow-up time of 29.4 months. No CX-01-associated serious adverse events occurred. Median day to an untransfused platelet count of at least 20 × 109/L was 21. CX-01 is well tolerated when combined with intensive therapy for AML and appears associated with enhanced count recovery and treatment efficacy.