Organizing a Regional In-Person Medical Student Symposium in Neuroscience and Neurosurgery Research: A How-To Guide.

BACKGROUND: Medical students are increasingly seeking out research opportunities to build their skills and network with future colleagues. Medical student-led conferences are an excellent endeavor to achieve this goal. METHODS: The American Association of Neurological Surgeons (AANS) student chapter at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell designed an in-person medical student research symposium alongside the Northwell Health Department of Neurosurgery. Post-conference feedback forms were sent out digitally to student attendees to evaluate event planning and execution and responses were given on a scale of 1-5 (5 being the highest score). RESULTS: In December 2023, the Northeast Medical Student Research Symposium (NMSRS) was held with over 80 participants and 52 medical student presenters. Keynote speakers delivered lectures geared towards students interested in neurosurgery and neuroscience research, followed by an interactive poster board session and resident/attending networking dinner. After the conference, students affirmed that they learned more about neuroscience research after the event (mean: 4.3), were more inclined to attend other neuroscience research events in the future (mean: 4.7), and would attend this event if held next year (mean: 4.8). The poster sessions (mean: 4.75) and keynote lectures (mean: 5) were the highest rated events, while the resident/attending networking dinner (mean: 3.6) was a potential area for improvement. CONCLUSION: Regional in-person conferences are an excellent way to foster interest in neurosurgery and neuroscience research, network with like-minded peers, and prepare students for presentations at national meetings.

A Quantitative Assessment of ChatGPT as a Neurosurgical Triaging Tool.

BACKGROUND AND OBJECTIVES: ChatGPT is a natural language processing chatbot with increasing applicability to the medical workflow. Although ChatGPT has been shown to be capable of passing the American Board of Neurological Surgery board examination, there has never been an evaluation of the chatbot in triaging and diagnosing novel neurosurgical scenarios without defined answer choices. In this study, we assess ChatGPT's capability to determine the emergent nature of neurosurgical scenarios and make diagnoses based on information one would find in a neurosurgical consult. METHODS: Thirty clinical scenarios were given to 3 attendings, 4 residents, 2 physician assistants, and 2 subinterns. Participants were asked to determine if the scenario constituted an urgent neurosurgical consultation and what the most likely diagnosis was. Attending responses provided a consensus to use as the answer key. Generative pretraining transformer (GPT) 3.5 and GPT 4 were given the same questions, and their responses were compared with the other participants. RESULTS: GPT 4 was 100% accurate in both diagnosis and triage of the scenarios. GPT 3.5 had an accuracy of 92.59%, slightly below that of a PGY1 (96.3%), an 88.24% sensitivity, 100% specificity, 100% positive predictive value, and 83.3% negative predicative value in triaging each situation. When making a diagnosis, GPT 3.5 had an accuracy of 92.59%, which was higher than the subinterns and similar to resident responders. CONCLUSION: GPT 4 is able to diagnose and triage neurosurgical scenarios at the level of a senior neurosurgical resident. There has been a clear improvement between GPT 3.5 and 4. It is likely that the recent updates in internet access and directing the functionality of ChatGPT will further improve its utility in neurosurgical triage.

Editorial Commentary: Gracilis-Sparing Anterior Cruciate Ligament Hamstring Graft Reconstruction Is Less Invasive Than Semitendinosus-Gracilis Graft Harvest, and Shows No Clinical Difference in Outcomes With Grafts Greater Than 8 mm in Diameter.

Although patellar tendon grafts are most commonly used for anterior cruciate ligament reconstruction in the United States, hamstring autograft is most commonly used worldwide. Hamstring advantages include easy, quick harvest; low morbidity; ease of rehabilitation (compared with patellar tendon grafts); and relatively less pain. Historically, both the semitendinosus (ST) and gracilis are harvested, but by doubling, tripling, or quadrupling the ST to achieve an 8-mm graft, the gracilis can be spared, resulting in less knee flexion weakness. However, recent research has shown no clinically important difference between ST and ST-gracilis patient outcomes.

The Effect of Radial Inclination on the Stage of Kienbock Disease at the Time of Initial Diagnosis.

BACKGROUND: Negative ulnar variance is a widely accepted risk factor for the development of Kienbock disease (KD). Variation in radial inclination has been proposed as a risk factor, but evidence thus far has been inconclusive. We aim to clarify the relationship between radial inclination and KD. METHODS: A retrospective analysis of all KD patients from a single institution from 2007 to 2021 was conducted. Radiographs were reviewed to measure anatomic parameters and stage of disease. An exploratory multinomial regression model was created to examine the association of patient age, radial height, ulnar variance, radial inclination, volar tilt, scapholunate angle, duration of symptoms prior to evaluation, history of wrist trauma, and diagnosis of diabetes with stage of disease. RESULTS: Fifty-seven cases of KD were identified, with a mean duration of disease of 33.3 months. A history of trauma to the wrist was common (53%) and significantly associated with stage of disease at initial presentation. Twenty-seven cases (47%) were stage IIIB or greater. The average initial radial inclination, radial height, and ulnar variance was 21.9°, 10.7 mm, and -1.23 mm, respectively. A multinominal logistic regression model revealed decreased initial radial inclination is associated with Lichtman stage IIIB or greater at the time of initial patient presentation. CONCLUSIONS: A correlation exists between decreased radial inclination and more advanced KD at presentation, suggesting this may be a risk factor for disease progression. This correlation is strengthened by our finding of decreased ulnar variance being associated with later stage at presentation, which is one of the most widely accepted proposed risk factors for development and progression of disease. LEVEL OF EVIDENCE: IV.

Bioconjugated liquid-like solid enhances characterization of solid tumor - chimeric antigen receptor T cell interactions.

Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable success as an immunotherapy for hematological malignancies, and its potential for treating solid tumors is an active area of research. However, limited trafficking and mobility of T cells within the tumor microenvironment (TME) present challenges for CAR T cell therapy in solid tumors. To gain a better understanding of CAR T cell function in solid tumors, we subjected CD70-specific CAR T cells to a challenge by evaluating their immune trafficking and infiltration through a confined 3D microchannel network in a bio-conjugated liquid-like solid (LLS) medium. Our results demonstrated successful CAR T cell migration and anti-tumor activity against CD70-expressing glioblastoma and osteosarcoma tumors. Through comprehensive analysis of cytokines and chemokines, combined with in situ imaging, we elucidated that immune recruitment occurred via chemotaxis, and the effector-to-target ratio plays an important role in overall antitumor function. Furthermore, through single-cell collection and transcriptomic profiling, we identified differential gene expression among the immune subpopulations. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach. STATEMENT OF SIGNIFICANCE: The use of specialized immune cells named CAR T cells to combat cancers has demonstrated remarkable success against blood cancers. However, this success is not replicated in solid tumors, such as brain or bone cancers, mainly due to the physical barriers of these solid tumors. Currently, preclinical technologies do not allow for reliable evaluation of tumor-immune cell interactions. To better study these specialized CAR T cells, we have developed an innovative in vitro three-dimensional model that promises to dissect the interactions between tumors and CAR T cells at the single-cell level. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach.

Three-Dimensional Bioconjugated Liquid-Like Solid (LLS) Enhance Characterization of Solid Tumor - Chimeric Antigen Receptor T cell interactions.

Cancer immunotherapy offers lifesaving treatments for cancers, but the lack of reliable preclinical models that could enable the mechanistic studies of tumor-immune interactions hampers the identification of new therapeutic strategies. We hypothesized 3D confined microchannels, formed by interstitial space between bio-conjugated liquid-like solids (LLS), enable CAR T dynamic locomotion within an immunosuppressive TME to carry out anti-tumor function. Murine CD70-specific CAR T cells cocultured with the CD70-expressing glioblastoma and osteosarcoma demonstrated efficient trafficking, infiltration, and killing of cancer cells. The anti-tumor activity was clearly captured via longterm in situ imaging and supported by upregulation of cytokines and chemokines including IFNg, CXCL9, CXCL10, CCL2, CCL3, and CCL4. Interestingly, target cancer cells, upon an immune attack, initiated an "immune escape" response by frantically invading the surrounding microenvironment. This phenomenon however was not observed for the wild-type tumor samples which remained intact and produced no relevant cytokine response. Single cells collection and transcriptomic profiling of CAR T cells at regions of interest revealed feasibility of identifying differential gene expression amongst the immune subpopulations. Complimentary 3D in vitro platforms are necessary to uncover cancer immune biology mechanisms, as emphasized by the significant roles of the TME and its heterogeneity.

Implementation of a Preoperative Huddle at a Level 1 Trauma Center.

OBJECTIVE: Medical errors resulting in patient harm still occur at an alarmingly high rate. Surgery is a high-risk area that can frequently result in patient harm if errors occur. There is a need for standardization of communication and processes to decrease errors. We sought to determine whether the implementation of a preoperative huddle at our hospital could standardize communication and decrease medical errors. METHODS: A unique preoperative huddle was developed and implemented at a level 1 trauma center. We reviewed data before and after the implementation of the preoperative huddle including patient surveys and comments, the percentage of on-time operating room (OR) starts, OR turnover times, and the number of sentinel events. RESULTS: After huddle implementation, we observed a trend of improvement in our patient survey results on patient's perception that the doctors/nurses explained the procedure understandably after huddle implementation. There was a statistically yet limited clinically significant increase in OR turnover time from 37 to 40 minutes (P < 0.001). There was also an increase in on-time OR starts from 37% to 45% (P < 0.001). We observed a decrease in the number of sentinel events, with only 1 occurring each year since implementation. CONCLUSIONS: A preoperative huddle was successfully implemented at a level 1 trauma hospital and helped standardize communication without significantly disrupting workflow. To our knowledge, this method of preoperative huddling has not been previously described in the literature.

Time domain DNP at 1.2 T.

We present the results of an experimental pulsed DNP study at 1.2 T (33.5 GHz/51 MHz electron and 1H Larmor frequencies, respectively). The results include a comparison of constant-amplitude NOVEL (CA-NOVEL), ramped-amplitude NOVEL (RA-NOVEL) and the frequency-swept integrated solid effect (FS-ISE) experiments all of which were performed at the NOVEL matching condition, ω1S=ω0I, where ω1S is the electron Rabi frequency andω0I the proton Larmor frequency. To the best of our knowledge, this is the first pulsed DNP study carried out at field higher than X-band (0.35 T) using the NOVEL condition. A combination of high microwave power (∼150 W) and a microwave cavity with a high Q (∼500) allowed us to satisfy the NOVEL matching condition. We also observed stretched solid effect (S2E) contributions in the Zeeman field profiles when chirped pulses are applied. Furthermore, the high quality factor of the cavity limits the concentration of the radical to ∼5 mM and generates a hysteresis in the FS-ISE experiments. Nevertheless, we observe very high DNP enhancements that are comparable to the results at X-band. These promising outcomes suggest the importance of further studies at even higher fields that delineate the instrumentation and methods required for time domain DNP.

Current Procedural Terminology-based Procedure Categorization Enhances Cost Prediction of Medicare Severity Diagnosis Related Group in Spine Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim of this study was to analyze how a Current Procedural Terminology (CPT)-based categorization method can predict cost variation in surgical spine procedures. SUMMARY OF BACKGROUND DATA: Neck and back disorders affect a majority of the adult population and account for tens of billions of dollars in health care spending each year. In the era of bundled payments and value-based reimbursement, it is imperative for surgeons to identify sources of cost variability across surgical spine procedures. Historically, this has been accomplished using Medicare Severity Diagnosis Related Group (MS-DRG) codes, but they utilize an overly simplistic categorization of surgical procedures. The specificity and familiarity of the CPT coding structure makes it a better option for categorizing differences in surgical decision making and technique. METHODS: Hospital billing data for patients undergoing a surgical spine procedure requiring an overnight, in-patient stay was retrospectively collected over 4 fiscal years (2012-2016) from a single health care system. Linear regression analysis was performed to assess the correlation between cost variation and: spine-specific MS-DRG codes; a novel CPT-based categorization method; and the combination of MS-DRG codes and CPT-based categorization. RESULTS: There were 5020 surgical procedures were analyzed with respect to 16 different MS-DRG codes and 30 distinct CPT-based surgical categories (CSCs). Linear regression results were: MS-DRG R2 = 0.6545 (P < 0.001); CSC R2 = 0.5709 (P < 0.001); and R2 = 0.744 for the combined MS-DRG and CSC methods (P < 0.05). Median difference between the actual and predicted cost for the combined model was -$261.00, compared with -$727.50 for the CSC model and -$478.70 for the MS-DRG model. CONCLUSION: Addition of the CPT-based categorization method to MS-DRG coding provides an enhanced method to evaluate the association between predicted and actual cost when using linear regression analysis to assess cost variation in spine surgery.Level of Evidence: 3.

Surgeons lack of agreement on determining preoperative radiographic and clinical shoulder balance in adolescent and adult idiopathic scoliosis patients.

PURPOSE: Preoperative shoulder balance is an important factor in determining the upper instrumented vertebrae (UIV). In adolescent and adult idiopathic scoliosis (AIS/AdIS) patients, we studied the intraobserver and interobserver reliability of spinal surgeons' assessment of preoperative shoulder balance using X-rays (XR) and anterior/posterior photographs. METHODS: An observational review of a prospective multicenter database (AIS Lenke Type 1/5/6) and prospective single-institution database (AdIS) was conducted. Ten spine surgeons reviewed AIS cases; 12 spine surgeons reviewed AdIS cases. Surgeons rated the higher shoulder: left/right/same/unsure. Reliability was calculated using Fleiss' kappa coefficient. RESULTS: Among 145 Type 1 AIS cases, intraobserver reliability was moderate-to-substantial: XR (κ = 0.59), anterior photographs (κ = 0.68), posterior photographs (k = 0.65). Interobserver reliability was fair to moderate for XR (κ = 0.31), anterior photographs (κ = 0.20), and posterior photographs (κ = 0.30). Among 52 Type 5/6 AIS cases, intraobserver reliability was substantial: XR (κ = 0.70), anterior photographs (κ = 0.76), posterior photographs (κ = 0.71). Interobserver reliability was fair to moderate for XR (κ = 0.49), anterior photographs (κ = 0.47), and posterior photographs (κ = 0.36). Among 66 AdIS cases, intraobserver reliability was substantial: XR (κ = 0.68), anterior photographs (κ = 0.67), posterior photographs (κ = 0.69). Interobserver reliability was moderate for XR (κ = 0.45), anterior photographs (κ = 0.43), posterior photographs (κ = 0.49). Within Type 1 AIS patients, attendings had better intraobserver reliabilities compared to fellows using X-rays (κ = 0.61 vs. 0.53), yet no effect of surgeon experience was seen with clinical photographs. CONCLUSION: Though surgeons' ability to agree with themselves was moderate to substantial, surgeons' ability to agree with each other was fair to moderate. Combined measures to assess preoperative shoulder balance are needed for UIV selection.

A new modular radiographic classification of adult idiopathic scoliosis as an extension of the Lenke classification of adolescent idiopathic scoliosis.

PURPOSE: To propose and test the reliability of a radiographic classification system for adult idiopathic scoliosis. METHODS: A three-component radiographic classification for adult idiopathic scoliosis consisting of curve type, a lumbosacral modifier, and a global alignment modifier is presented. Twelve spine surgeons graded 30 pre-marked cases twice, approximately 1 week apart. Case order was randomized between sessions. RESULTS: The interrater reliability (Fleiss' kappa coefficient) for curve type was 0.660 and 0.798, for the lumbosacral modifier 0.944 and 0.965, and for the global alignment modifier 0.922 and 0.916, for round 1 and 2 respectively. Mean intrarater reliability was 0.807. CONCLUSIONS: This new radiographic classification of adult idiopathic scoliosis maintains the curve types from the Lenke classification and introduces the lumbosacral and global alignment modifiers. The reliability of the lumbosacral modifier and global alignment modifier shows near perfect agreement, and sets the foundation for further studies to validate the reliability, utility, and applicability of this classification system.

Does the Global Alignment and Proportion score overestimate mechanical complications after adult spinal deformity correction?

OBJECTIVE: The goal of this study was to validate the Global Alignment and Proportion (GAP) score in a cohort of patients undergoing adult spinal deformity (ASD) surgery. The GAP score is a novel measure that uses sagittal parameters relative to each patient's lumbosacral anatomy to predict mechanical complications after ASD surgery. External validation is required. METHODS: Adult ASD patients undergoing > 4 levels of posterior fusion with a minimum 2-year follow-up were included. Six-week postoperative standing radiographs were used to calculate the GAP score, classified into a spinopelvic state as proportioned (P), moderately disproportioned (MD), or severely disproportioned (SD). A chi-square analysis, receiver operating characteristic curve, and Cochran-Armitage analysis were performed to assess the relationship between the GAP score and mechanical complications. RESULTS: Sixty-seven patients with a mean age of 52.5 years (range 18-75 years) and a mean follow-up of 2.04 years were included. Patients with < 2 years of follow-up were included only if they had an early mechanical complication. Twenty of 67 patients (29.8%) had a mechanical complication. The spinopelvic state breakdown was as follows: P group, 21/67 (31.3%); MD group, 23/67 (34.3%); and SD group, 23/67 (34.3%). Mechanical complication rates were not significantly different among all groups: P group, 19.0%; MD group, 30.3%; and SD group, 39.1% (χ2 = 1.70, p = 0.19). The rates of mechanical complications between the MD and SD groups (30.4% and 39.1%) were less than those observed in the original GAP study (MD group 36.4%-57.1% and SD group 72.7%-100%). Within the P group, the rates in this study were higher than in the original study (19.0% vs 4.0%, respectively). CONCLUSIONS: The authors found no statistically significant difference in the rate of mechanical complications between the P, MD, and SD groups. The current validation study revealed poor generalizability toward the authors' patient population.

Virtual Spine: A Novel, International Teleconferencing Program Developed to Increase the Accessibility of Spine Education During the COVID-19 Pandemic.

BACKGROUND: The coronavirus identified in 2019 (COVID-19) pandemic effectively ended all major spine educational conferences in the first half of 2020. In response, the authors formed a "virtual" case-based conference series directed at delivering spine education to health care providers around the world. We herein share the technical logistics, early participant feedback, and future direction of this initiative. METHODS: The Virtual Global Spine Conference (VGSC) was created in April 2020 by a multiinstitutional team of spinal neurosurgeons and a neuroradiologist. Biweekly virtual meetings were established wherein invited national and international spine care providers would deliver case-based presentations on spine and spine surgery-related conditions via teleconferencing. Promotion was coordinated through social media platforms such as Twitter. RESULTS: VGSC recruited more than 1000 surgeons, trainees, and other specialists, with 50-100 new registrants per week thereafter. An early survey to the participants, with 168 responders, indicated that 92% viewed the content as highly valuable to their practice and 94% would continue participating post COVID-19. Participants from the United States (29%), Middle East (16%), and Europe (12%) comprised the majority of the audience. Approximately 52% were neurosurgeons, 18% orthopedic surgeons, and 6% neuroradiologists. A majority of participants were physicians (55%) and residents/fellows (21%). CONCLUSIONS: The early success of the VGSC reflects a strong interest in spine education despite the COVID-19 pandemic and social distancing guidelines. There is widespread opinion, backed by our own survey results, that many clinicians and trainees want to see "virtual" education continue post COVID-19.

Diverse approaches to predicting drug-induced liver injury using gene-expression profiles.

BACKGROUND: Drug-induced liver injury (DILI) is a serious concern during drug development and the treatment of human disease. The ability to accurately predict DILI risk could yield significant improvements in drug attrition rates during drug development, in drug withdrawal rates, and in treatment outcomes. In this paper, we outline our approach to predicting DILI risk using gene-expression data from Build 02 of the Connectivity Map (CMap) as part of the 2018 Critical Assessment of Massive Data Analysis CMap Drug Safety Challenge. RESULTS: First, we used seven classification algorithms independently to predict DILI based on gene-expression values for two cell lines. Similar to what other challenge participants observed, none of these algorithms predicted liver injury on a consistent basis with high accuracy. In an attempt to improve accuracy, we aggregated predictions for six of the algorithms (excluding one that had performed exceptionally poorly) using a soft-voting method. This approach also failed to generalize well to the test set. We investigated alternative approaches-including a multi-sample normalization method, dimensionality-reduction techniques, a class-weighting scheme, and expanding the number of hyperparameter combinations used as inputs to the soft-voting method. We met limited success with each of these solutions. CONCLUSIONS: We conclude that alternative methods and/or datasets will be necessary to effectively predict DILI in patients based on RNA expression levels in cell lines. REVIEWERS: This article was reviewed by Pawel P Labaj and Aleksandra Gruca (both nominated by David P Kreil).

Dynamic Cord Compression Causing Cervical Myelopathy.

Due to the highly mobile nature of the cervical spine, and the fact that most magnetic resonance imagings (MRIs) and computed tomography scans are obtained only in one single position, dynamic cord compression can be an elusive diagnosis that is often missed and not well-understood. In this context, dynamic MRI (dMRI) has been utilized to improve the diagnostic accuracy of cervical stenosis. We performed a literature review on dynamic cord compression in the context of cervical spondylotic myelopathy (CSM), with particular emphasis on the role of dMRI. Cadaveric studies report that the spinal cord lengthens in flexion and the spinal canal dimension increases, whereas the spinal cord relaxes and shortens in extension and the spinal canal decreases. These changes may lead to biomechanical stress in the spinal cord with movement, especially in patients with critical cervical stenosis. The majority of the studies using dMRI in CSM reported that this imaging modality is more sensitive at detecting cervical cord compression compared to routine MRIs done in a neutral position, especially with the neck in extension. Dynamic MRI was also useful to diagnose dynamic cervical cord compression after laminectomies in patients with clinical deterioration without evident cord compression on neutral static MRI. Finally, dMRI is more sensitive in detecting stenosis in patients with CSM than in those with ossification of the posterior longitudinal ligament (OPLL), likely because OPLL patients often have a more limited range of motion than CSM patients. Thus, dMRI is a promising new tool that can help spine surgeons in diagnosing and treating CSM.

Minimally invasive approach to the lumbosacral junction with a single position, 360° fusion.

Degenerative lumbar pathologies are commonly encountered at the lumbosacral junction. The transition from the mobile lumbar spine to the stiff sacroiliac segment results in high biomechanical stresses and can lead to disc degeneration, ligamentum flavum hypertrophy, neural foraminal stenosis, and other causes of pain or neurologic deficit. Surgical intervention at the lumbosacral junction must be tailored to maximize pain relief and relieve neural compression and reverse neurologic deficit while preserving the spine's natural biomechanical strength and flexibility and preventing the slow march of adjacent segment degeneration cranially into the thoracolumbar spine. It is our practice to offer combined anterior and posterior minimally invasive options when appropriate to maximize neural decompression and pain relief while ensuring proper segmental alignment and maximizing fusion rates through a minimally disruptive approach. In this article we detail a common presentation of lumbosacral pathology and the approach and considerations for a single position, minimally invasive anterior and posterior approach at the L5/S1 segment.

Topical probiotics: the unknowns behind their rising popularity.

OBJECTIVE: Topical probiotics have been used for skin care and treatment since the early 20th century. Over the past decade, there has been a dramatic surge of commercially-available topical probiotic products. We conducted a systematic search of clinical data relating to the use of topical probiotics and identified relevant clinical and regulatory gaps. METHODS: PubMed and Google Scholar searches were conducted for trials and reviews of probiotics. FDA definitions of cosmetics, drugs, and regulation of topical probiotics were reviewed. RESULTS: Topical probiotics have shown efficacy in a number of limited trials, particularly those involving the treatment of acne, atopic dermatitis, and rosacea. However, there is a paucity of literature on the safety profiles, mechanistic action, and therapeutic potential of topical probiotic products. Several regulatory gaps exist, including approval and classification of topical probiotic products by the FDA; currently there are no topical probiotic products the FDA has approved as drugs. CONCLUSION: With increasing popularity among the general public, but insufficient clinical data to demonstrate large-scale effectiveness and a thorough understanding of side effects, there is a need for further mechanistic and clinical investigation, as well as improved regulation and standardization of topical probiotic products.

Increased multimodality treatment options has improved survival for Hepatocellular carcinoma but poor survival for biliary tract cancers remains unchanged.

BACKGROUND: Primary hepatobiliary cancer incidence in the UK is rising and survival rates are low. Surgery is the main curative option for these cancers, but multimodality therapies are expanding. The aim of our original study was to determine trends in survival, over an 8-year period, of patients treated for primary hepatobiliary cancers at our tertiary referral Centre. METHOD: Patients treated for the most common types of primary hepatobiliary cancers, namely Hepatocellular carcinoma (HCC), Cholangiocarcinoma and Gallbladder cancer between January 2009 and December 2016 were retrospectively analysed from a prospective database linked to UK Hospital Episode Statistics data. RESULTS: A total of 1536 patients with primary hepatobiliary cancers were assessed and treatment plans formulated at our supra-regional specialist Hepatobiliary MDT. The primary hepatobiliary cancers treated were HCC (n = 836), Cholangiocarcinoma (n = 516), and Gallbladder cancer (n = 184). Survival for all the 3 cancers was significantly better with curative treatment. Overall median survival times were 350, 180, and 150 days respectively for HCC, Cholangiocarcinoma and Gallbladder cancer. Excluding best supportive care patients, the respective survival figures were 900, 600, and 400 days. Survival for HCC patients improved over time and was significantly increased in the final 3 years of the study (p ≤ 0.011 for all). Cholangiocarcinoma and Gallbladder cancer survivals were poor and did not change significantly over time. CONCLUSION: HCC outcome has improved in association with expanded multimodal therapies. Survivals for cholangiocarcinoma and gallbladder cancer remain poor in parallel with limited expansion of multimodal therapies highlighting an unmet therapeutic need for biliary tract cancers.

Current and emerging therapies for hand eczema.

Although hand eczema (HE) and chronic hand eczema (CHE) are common conditions with significant disease burden, they traditionally have had limited treatment options beyond topical and short-term systemic corticosteroids. We reviewed published and preliminary evidence on the current and emerging topical and systemic therapeutic agents for HE and CHE. The etiologies of various HE subtypes are discussed, and remaining knowledge and practice gaps are highlighted to encourage further investigations. A comprehensive search of ClinicalTrials.gov and PubMed was completed for clinical trials that utilized known and emerging treatment options for HE and CHE. Several agents that target IL-4 and IL-13 signaling, keratinocyte proliferation, inflammatory cytokine production, bacterial protein synthesis, and inflammatory mediator (TNF-α, JAK1, JAK2, and JAK3) proliferation are shown to be involved in the pathogenesis of CHE. Systemic agents include dupilumab, alitretinoin, acitretin, cyclosporine, azathioprine, and probiotics. Topical agents include delgocitinib, retapamulin, halometasone/triclosan, calcipotriol/betamethasone, tacrolimus, and pimecrolimus. These modalities have demonstrated varying degrees of clinical efficacy, evaluated by subjective assessments and scoring indexes. Targeted therapies are emerging for HE, but options are still limited, partially due to our narrow understanding of this heterogeneous condition. Additional and targeted therapeutic options are needed to match the rising prevalence and burden of HE. KEYPOINTS: Hand eczema (HE) is a heterogenous dermatosis with limited therapeutic options due to a lack of international guidelines regarding classification of HE subtypes and treatment. This review discusses current and emerging topical and systemic agents and their efficacies in the treatment of different types of hand eczema.

Data on items of AKUSSI in Alkaptonuria collected over three years from the United Kingdom National Alkaptonuria Centre and the impact of nitisinone.

Alkaptonuria is a rare genetic disorder characterized by a high level of circulating (and urine) homogentisic acid (HGA), which contributes to ochronosis when it is deposited in connective tissue as a pigmented polymer. In an observational study carried out by National AKU Centre (NAC) in Liverpool, a total of thirty-nine AKU patients attended yearly visits in varying numbers. At each visit a mixture of clinical, joint and spinal assessments were carried out and the results calculated to yield an AKUSSI (Alkaptonuria Severity Score Index), see "Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre" (Ranganath at el., 2018). The aim of this data article is to produce visual representation of the change in the components of AKUSSI over 3 years, through radar charts. The metabolic effect of nitisinone is shown through box plots.