Revised Grading System Research Articles

Proposed revision of the American Association for Surgery of Trauma Renal Organ Injury Scale: Secondary analysis of the Multi-institutional Genitourinary Trauma Study.

This study updates the American Association for the Surgery of Trauma (AAST) Organ Injury Scale (OIS) for renal trauma using evidence-based criteria for bleeding control intervention. This was a secondary analysis of a multicenter retrospective study including patients with high-grade renal trauma from seven level 1 trauma centers from 2013 to 2018. All eligible patients were assigned new renal trauma grades based on revised criteria. The primary outcome used to measure injury severity was intervention for renal bleeding. Secondary outcomes included intervention for urinary extravasation, units of packed red blood cells transfused within 24 hours, and mortality. To test the revised grading system, we performed mixed-effect logistic regression adjusted for multiple baseline demographic and trauma covariates. We determined the area under the curve (AUC) to assess accuracy of predicting bleeding interventions from the revised grading system and compared this to 2018 AAST OIS. Based on the 2018 OIS grading system, we included 549 patients with AAST grades III to V injuries and computed tomography scans (III, 52% [n = 284]; IV, 45% [n = 249]; and V, 3% [n = 16]). Among these patients, 89% experienced blunt injury (n = 491), and 12% (n = 64) underwent intervention for bleeding. After applying the revised grading criteria, 60% (n = 329) of patients were downgraded, and 4% (n = 23) were upgraded; 2.8% (n = 7) downgraded from grade V to IV, and 69.5% (n = 173) downgraded from grade IV to III. The revised renal trauma grading system demonstrated improved predictive ability for bleeding interventions (2018 AUC, 0.805; revised AUC, 0.883; p = 0.001) and number of units of packed red blood cells transfused. When we removed urinary injury from the revised system, there was no difference in its predictive ability for renal hemorrhage intervention. A revised renal trauma grading system better delineates the need for hemostatic interventions than the current AAST OIS renal trauma grading system. Diagnostic Test/Criteria; Level III.

Abstract 936: Clinicogenomic predictors for the pattern of failure in high-grade glioma

Abstract Background: High-grade gliomas, the most common primary brain tumors, are highly lethal, and treatment options remain limited. Despite advances in genomic technologies, there are few molecular biomarkers to guide precision medicine for high-grade glioma. Here, we aimed to identify the clinicogenomic features associated with its prognosis and recurrence patterns. Materials/Methods: Our single-institution retrospective analysis included 223 patients diagnosed with high-grade gliomas who underwent next-generation sequencing targeting 82 brain tumor-relevant genes. We categorized them according to the 2021 WHO classification, and their clinicopathological statuses, treatment characteristics, survival, and genomic profiles were analyzed. Results: The most common genomic variants were TERT promoter (51%), TP53 (39%), IDH1/2 (18%), NF1 (13%), ATRX (12%), PTEN (11%), PIK3CA (9%), SETD2 (7%), and H3F3A (6%) mutation. Regarding copy number variants, amplification of EGFR (21%), PDGFRA (11%), CDK4 (9%) and loss of CDKN2A/2B (55%), PTEN (29%), 19q (17%), NF2 (14%), and RB1 (10%) were the most common copy number aberrations. At a median follow-up of 18 months (range, 2-54 months), 174 patients (78%) had progression or recurrences. A total of 15.2% of our patients were re-classified under the 2021 WHO classification, and there was a clear separation of overall survival(OS) and progression-free survival(PFS) curves between grade 3 and 4 groups using the revised grading system. On multivariate cox regression analysis, MYCN amplification (HR 6.08, p = 0.002) and SETD2 mutation (HR 0.19, p =0.06) were independent predictors of OS and PFS. Conclusion: The assessment of genomic characteristics in conjunction with the pattern of failure for high-grade glioma aids in identifying patients who are likely to benefit from personalized medicine. The 2021 WHO grading system explains survival differences between grade 3 and 4 tumors better than the 2016 WHO classification dose. We identified SETD2 mutation and MYCN as prognostic biomarkers with potential therapeutic implications in patients with high-grade glioma. Citation Format: Joo Ho Lee, Byung-Hee Kang, Seungbok Lee. Clinicogenomic predictors for the pattern of failure in high-grade glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 936.

Prognostic significance of tumor budding thresholds in oral tongue squamous cell carcinoma.

Oral tongue squamous cell carcinoma (OTSCC) represents the most common malignancy of the oral cavity. Tumor budding (TB) is a reliable prognostic factor in OTSCC; however, a standardized scoring system is not still validated. The study aims to evaluate the prognostic role of TB in 211 OTSCC patients treated between 1997 and 2018. TB was evaluated on hematoxylin and eosin-stained sections in the hotspot area of the infiltrative front (×200-magnification). It was scored using a two-tier system, a three-tier system, and according to BD-model and revised-Grading system. Univariate and multivariate Cox regression analyses of disease-specific survival (DSS) and disease-free survival (DFS) were performed. A p<0.05 was considered as statistically significant. The two-tier and three-tier systems resulted an independent prognostic factor of DSS. High-risk patients had a 2.21 and 3.08 times increased probability of poor DSS compared with low-risk group. It is significantly increased even for intermediate-risk group. No significant differences emerged classifying patients according to BD-model and revised-Grading system. These data confirm the prognostic value of TB in predicting DSS in OTSCC. Classifying patients into two groups using the 5-bud cutoff significantly discriminates their outcomes. Since the established role of DOI and the poor prognostic value of grading, TB could be considered an independent prognostic marker.

Revision of the AAST grading scale for acute cholecystitis with comparison to physiologic measures of severity.

Grading systems for acute cholecystitis are essential to compare outcomes, improve quality, and advance research. The American Association for the Surgery of Trauma (AAST) grading system for acute cholecystitis was only moderately discriminant when predicting multiple outcomes and underperformed the Tokyo guidelines and Parkland grade. We hypothesized that through additional expert consensus, the predictive capacity of the AAST anatomic grading system could be improved. A modified Delphi approach was used to revise the AAST grading system. Changes were made to improve distribution of patients across grades, and additional key clinical variables were introduced. The revised version was assessed using prospectively collected data from an AAST multicenter study. Patient distribution across grades was assessed, and the revised grading system was evaluated based on predictive capacity using area under receiver operating characteristic curves for conversion from laparoscopic to an open procedure, use of a surgical "bail-out" procedure, bile leak, major complications, and discharge home. A preoperative AAST grade was defined based on preoperative, clinical, and radiologic data, and the Parkland grade was also substituted for the operative component of the AAST grade. Using prospectively collected data on 861 patients with acute cholecystitis the revised version of the AAST grade has an improved distribution across all grades, both the overall grade and across each subscale. A higher AAST grade predicted each of the outcomes assessed (all p ≤ 0.01). The revised AAST grade outperformed the original AAST grade for predicting operative outcomes and discharge disposition. Despite this improvement, the AAST grade did not outperform the Parkland grade or the Emergency Surgery Score. The revised AAST grade and the preoperative AAST grade demonstrated improved discrimination; however, a purely anatomic grade based on chart review is unlikely to predict outcomes without addition of physiologic variables. Follow-up validation will be necessary. Diagnostic Test or Criteria, Level IV.

Bringing clerkship grading back to the bedside.

The hallmark of medical education is learning from patients through interactions at the bedside. However, many medical schools incorporate clinical clerkship grading systems that incentivize time away from patient care activities to focus on examinations of medical knowledge. The purpose of this innovation was to develop a grading system that encouraged development of competencies beyond medical knowledge, including patient care, communication, and professionalism skills. In 2016, the authors convened a diverse workgroup to reform the clerkship grading approach at their institution. The group reviewed relevant literature and discussed approaches used by other institutions. They developed a competency-based criterion system. For each of four competency domains (patient care, medical knowledge (examination score), professionalism, and communication/teamwork), students received a designation of inadequate, competent, or exemplary. The highest grade ("honors") was awarded to students who met the criteria for exemplary performance in at least two domains. It was a primarily compensatory model, although to achieve competency (pass) scoring was non-compensatory (acceptable performance in all categories). A total of 231 medical students received 1499 clerkship grades during the 2018-2019year. Compared to previous years, more students (40% vs. 15%) received honors. A substantial proportion (43%) received honors without achieving an exemplary designation in the medical knowledge domain (i.e., standardized examination). The revised grading system provided several avenues for students to excel and receive honors in their clerkships allowing for recognition of students who excelled in patient care-related areas other than standardized examinations.

Complete Responses in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients on a Weekly Dosing Schedule of Vibecotamab (XmAb14045), a CD123 x CD3 T Cell-Engaging Bispecific Antibody; Initial Results of a Phase 1 Study

Complete Responses in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients on a Weekly Dosing Schedule of Vibecotamab (XmAb14045), a CD123 x CD3 T Cell-Engaging Bispecific Antibody; Initial Results of a Phase 1 Study

Revised AAST scale for splenic injury (2018): does addition of arterial phase on CT have an impact on the grade?

To determine whether an additional arterial phase (AP) leads to a change in the grade of splenic injury according to the 2018 revision of the AAST Organ Injury Scale, which has incorporated vascular injuries into the grading system and also to study its impact on management. In this retrospective study, 527 patients who sustained blunt abdominal trauma and had underwent dual-phase CT (AP and portal venous phase (PVP)) from December 2014 to October 2016 (23months) were included. Two experienced radiologists independently graded the splenic injury according to the revised system in 2 blinded ways (AP + PVP and PVP alone). Receiver operator characteristic (ROC) curves were generated for grade of injury on both the phases for all splenic interventions. Splenic injuries were detected in 154 patients, and splenic vascular injuries were detected in 52 of them. Of these, 22 vascular injuries were detected only on the AP, leading to a change in the grade of injury according to the new system in 18 patients. The AUC for ROC curves was generated for the grade of injury on AP + PVP vs. PVP alone for angioembolization (0.80 vs. 0.71, p value 0.002), and all splenic interventions (0.89 vs. 0.83, p value 0.003) showed higher AUC for AP + PVP. Addition of AP leads to a significant change in the grading of splenic injuries according to the revised grading system due to increased detection of vascular injuries. Accurate classification of splenic injuries using additional AP would lead to better triage of patients for splenic interventions or conservative management.

Assessment of the Effects of Carcass Traits and Slaughter Age on the Carcass Grades of Hanwoo Steers Based on the Revised Grading System of Beef Carcasses

Assessment of the Effects of Carcass Traits and Slaughter Age on the Carcass Grades of Hanwoo Steers Based on the Revised Grading System of Beef Carcasses

A study to further develop and refine carpal tunnel syndrome (CTS) nerve conduction grading tool

BackgroundThe severity of carpal tunnel syndrome (CTS) may be categorised in a number of ways utilising one of a range of presently available grading tools. The grading systems proposed by Bland and Padua are the most commonly used, however, both have limitations, which are discussed in detail in this paper.The aim of this research is to establish, using the best available evidence, a clinically appropriate revision of the current CTS nerve conduction grading tool, and to compare with existing grading tools used in UK Neurophysiology clinics. The revised scale is designed from a clinical physiologist perspective and based on the numerical values of nerve conduction findings.The proposed revised grading system is based on more nuanced, descriptive categories, ranging from Normal to Early, Mild Sensory, Mild Sensory Motor, Moderate Sensory, Moderate Sensory Motor, Severe Sensory Motor, Extremely Severe Sensory Motor, and Complete absence.MethodA total of 1123 patients (2246 hands) were included in this study, with the aim of evaluating the revised grading system. Data was collected based on the extensive and detailed grading systems previously described by Bland and Padua. All data was recorded numerically to ensure methodological reliability.ResultOf the 2246 patients’ hands tested, the nerve conduction was graded as normal in 968 hands; nerve conduction showed early changes in 271 hands; mild sensory changes in 215 hands, mild changes in both motor and sensory response in 51 hands; moderate sensory changes in 134 hands; moderate sensory and motor changes in 356 hands; severe changes in motor and sensory responses in 204 hands; extremely severe sensory and motor changes in 33 hands and complete absence of response in 14 hands.ConclusionThe revised grading tool could offer a more numerical grading to the Clinical Physiologist and could help the surgeon to ascertain the level of severity in order to decide on either a conservative or surgical approach to treatment if they decide to use the proposed grading which could support them to defend their decision in cases of litigation.

Lack of Pathological Response of Rectal Cancer to Neoadjuvant Chemoradiotherapy is Associated with Poorer Long-Term Oncological Outcomes

Purpose: Tumor regression scores are used to evaluate local response to preoperative treatment. Complete pathological response (tumor regression score=0) is associated with excellent prognosis. In this study we evaluated the prevalence and impact of poor-to-no pathological response to neoadjuvant treatment (tumor regression score=3), based on a recently revised grading system on long term oncologic outcomes among rectal cancer patients. Methods: This retrospective study included rectal cancer patients who received. neoadjuvant chemoradiotherapy and surgical resection at our medical center. Pathological specimens were ren evaluated and graded (grades 0-3) based on the revised tumor regression scores. Disease free survival and cancer specific survival rates were documented and matched with the patients’ tumor regression scores. Results: Initially 78 patients were included. 6 patients were later excluded from the long-term follow up since they developed disease progression during neoadjuvant treatment. Among the other 72 patients, 38 (52.8%) were classified as tumor regression score=3 (no response) and 34 (47.2%) tumor regression score=0-2 (any level of response). Conversion from laparoscopy to open surgery was higher in the tumor regression score=3 group (21% vs. 2.9%, p=0.02). Follow-up ranged from 5 months to 12 years. Nine (12.5%) patients experienced disease recurrence, 8 with tumor regression score=3. Most recurrences were metastases to liver and lungs. Disease free survival was lower in tumor regression score=3 patients as compared to tumor regression score=0-2. Conclusions: Non-responders to neoadjuvant therapy are at higher risk for disease recurrence, conversion to open surgery and disease-related mortality. Systemic recurrence of tumor regression score=3 tumors suggests an aggressive biology of these tumors. Further studies are needed to characterize tumors that are less likely to respond to radiotherapy and to personalize preoperative treatment decisions.

A revised grading system for the Tinnitus Handicap Inventory based on a large clinical population

Objective: Tinnitus Handicap Inventory (THI) is one of the world’s most commonly used tools to assess tinnitus severity. The aim of the current study was to establish a revised THI grading system using standard Z-scores and percentiles.Design: Cross-sectional observational study.Study sample: Adult patients (1042 participants – 518 (49.7%) female and 524 (50.3%) male) reporting tinnitus duration of a minimum of 6 months with complete documentation on patient’s clinical status (age, gender, tinnitus duration and laterality, tinnitus handicap based on THI and hearing status based on pure-tone audiometry) were included in the study.Results: Multivariate analysis of variance was used to analyse the effects of gender and hearing loss on THI scores and revealed there was a significant effect of both. Consequently, separate grading systems for women and men, as well as for subjects with normal hearing and hearing loss, is proposed.Conclusions: Our findings are generally consistent with existing grading. Normative values proposed for THI scores, based on a large group of tinnitus patients, could be useful to guide decisions about appropriate intervention options or to evaluate treatment outcomes.

Predicting early post-operative remission in pituitary adenomas: evaluation of the modified knosp classification.

Cavernous sinus invasion by pituitary adenomas is an important prognostic factor for evaluating the possibilities of complete remission and to guide patient management. A widely used Magnetic Resonance Imaging grading system, suggested by Knosp in 1993, has recently been revised by the same group. The aims of our study were to apply this revised grading system to our surgical series, to determine its association with surgical outcomes, gross-total resection (GTR) and endocrinological remission (ER), paying particular attention to grades 3A and 3B, which represent the novelty of this revised classification. We included consecutive patients who underwent endoscopic endonasal surgery for a macroadenoma from September 2012 to December 2016. MRI images were reviewed and classified according to the revised Knosp classification. Surgical reports indicated the intra-operative CS invasion. GTR and ER were evaluated on 3-months post-operative MRI and endocrine evaluation. 254 patients were included in this study. We found a total rate of cavernous sinus invasion of 18.4%. Different outcomes were observed for each grade, with an increased rate of cavernous sinus invasion with each grade. Per-operative rates of invasion were 61.5 and 78.6% in grades 3A and 3B respectively. GTR was negatively correlated with the grade, while rates were 55.8% and 30.0% for grades 3A and 3B respectively. The revised Knosp radiological classification contributes to the prediction of surgical outcomes and early ER in pituitary adenomas. To manage, as precisely as possible, the risk of early recurrence in pituitary adenomas, clinicians should also consider other recognized prognostic factors, such as the proliferative status of the tumor.

Field testing of the revised neuropathic pain grading system in a cohort of patients with neck and upper limb pain.

Background and aims In 2008, the International Association for the Study of Pain Special Interest Group on Neuropathic Pain (NeuPSIG) proposed a clinical grading system to help identify patients with neuropathic pain (NeP). We previously applied this classification system, along with two NeP screening tools, the painDETECT (PD-Q) and Leeds Assessment of Neuropathic Symptoms and Signs pain scale (LANSS), to identify NeP in patients with neck/upper limb pain. Both screening tools failed to identify a large proportion of patients with clinically classified NeP, however a limitation of our study was the use of a single clinician performing the NeP classification. In 2016, the NeuPSIG grading system was updated with the aim of improving its clinical utility. We were interested in field testing of the revised grading system, in particular in the application of the grading system and the agreement of interpretation of clinical findings. The primary aim of the current study was to explore the application of the NeuPSIG revised grading system based on patient records and to establish the inter-rater agreement of detecting NeP. A secondary aim was to investigate the level of agreement in detecting NeP between the revised NeuPSIG grading system and the LANSS and PD-Q. Methods In this retrospective study, two expert clinicians (Specialist Pain Medicine Physician and Advanced Scope Physiotherapist) independently reviewed 152 patient case notes and classified them according to the revised grading system. The consensus of the expert clinicians' clinical classification was used as "gold standard" to determine the diagnostic accuracy of the two NeP screening tools. Results The two clinicians agreed in classifying 117 out of 152 patients (ICC 0.794, 95% CI 0.716-850; κ 0.62, 95% CI 0.50-0.73), yielding a 77% agreement. Compared to the clinicians' consensus, both LANSS and PD-Q demonstrated limited diagnostic accuracy in detecting NeP (LANSS sensitivity 24%, specificity 97%; PD-Q sensitivity 53%, specificity 67%). Conclusions The application of the revised NeP grading system was feasible in our retrospective analysis of patients with neck/upper limb pain. High inter-rater percentage agreement was demonstrated. The hierarchical order of classification may lead to false negative classification. We propose that in the absence of sensory changes or diagnostic tests in patients with neck/upper limb pain, classification of NeP may be further improved using a cluster of clinical findings that confirm a relevant nerve lesion/disease, such as reflex and motor changes. The diagnostic accuracy of LANSS and PD-Q in identifying NeP in patients with neck/upper limb pain remains limited. Clinical judgment remains crucial to diagnosing NeP in the clinical practice. Implications Our observations suggest that in view of the heterogeneity in patients with neck/upper limb pain, a considerable amount of expertise is required to interpret the revised grading system. While the application was feasible in our clinical setting, it is unclear if this will be feasible to apply in primary health care settings where early recognition and timely intervention is often most needed. The use of LANSS and PD-Q in the identification of NeP in patients with neck/upper limb pain remains questionable.

Oral epithelial dysplasia: Classifications and clinical relevance in risk assessment of oral potentially malignant disorders.

After more than a decade, the World Health Organization (WHO) published the revised grading system for oral epithelial dysplasia in 2017. The revised classification has changes reflecting our evolution of understanding of the dysplastic process. Although the WHO 2017 three-tier grading system is the gold standard for histological diagnosis of oral potentially malignant disorders, it has certain limitations. Suggestions to overcome these limitations include the use of clinical determinants and molecular markers to supplement the grading system. It has also been suggested that a two-tier system may be more reproducible and clinically translatable for better management. These advances in the understanding of epithelial dysplasia are very important globally and for us in the Indian subcontinent, given the prevalence of habits (tobacco/areca nut) and burden of oral cancer in this part of the world. The following review traces the evolution of the grading system of dysplasia, its relevance and clinical utility.

Complete Responses in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients on a Weekly Dosing Schedule of XmAb14045, a CD123 x CD3 T Cell-Engaging Bispecific Antibody: Initial Results of a Phase 1 Study

Background: Blasts and leukemic stem cells of acute myeloid leukemia (AML) as well as several other hematologic malignancies express CD123, potentially providing a target for novel therapies. XmAb14045 (also known as SQZ622) is a potent bispecific antibody targeting both CD123 and CD3 that stimulates targeted T cell-mediated killing of CD123-expressing cells, regardless of T cell antigen specificity. It is a full-length immunoglobulin molecule designed to be dosed intermittently, in contrast to smaller constructs that are referred to as “DART” or “BiTE” bispecific antibodies that require a continuous infusion.Methods: Patients with relapsed or refractory AML, B cell acute lymphoblastic leukemia (B-ALL), blast phase chronic myelogenous leukemia, or blastic plasmacytoid dendritic cell neoplasm were eligible to enroll on this first-in-human, multicenter, open-label phase 1 dose-escalation study (XmAb14045-01) with standard 3+3 design. The primary objective was to estimate the maximum tolerated dose (MTD) or recommended dose and schedule of XmAb14045. Secondary objectives included safety, preliminary antileukemic activity, and pharmacokinetics/pharmacodynamics of XmAb14045. Treatment was administered weekly in 28 day cycles, using a weight-based dose with a single dose level in Part A and, in Part B, an initial priming dose on Day 1 followed by an escalated dose on subsequent weeks. Premedication to prevent cytokine release syndrome (CRS) was instituted as needed and included a steroid, acetaminophen, and diphenhydramine. Patients were premedicated at all XmAb14045 doses ≥0.075 µg/kg. Therapy was continued for as long as tolerated and there was continuing evidence of therapeutic benefit in the opinion of the investigator. Treatment response was assessed by the 2017 European LeukemiaNet (ELN) criteria after Cycle 1 and after each odd-numbered cycle. CRS was graded using the CRS revised grading system (Lee et al., Blood, 2014).Results: At data cut-off, 64 patients have been treated to date, 63 with relapsed/refractory AML and 1 with B-ALL. Patients had a median age of 61 years and were heavily pretreated (median of 3 prior therapies [range 1-8], including 19 [30%] who had undergone prior allogeneic stem cell transplantation). The recommended dose for Part A was 1.3 µg/kg after a single dose-limiting toxicity of Grade 4 CRS at 2.3 µg/kg; no MTD has been identified. CRS or its component symptoms was the most common treatment-emergent adverse event (TEAE). CRS episodes began within approximately 1-4 hours of the start of drug infusion and occurred in 49 of 64 patients (77%). Seven patients (11%) developed Grade ≥3 CRS, the majority of these on the first dose. There were no CRS-related deaths. Excluding CRS-related events, additional TEAEs occurring in >10% of patients included fatigue (31%), febrile neutropenia (30%), peripheral edema (30%), cough (23%), elevated hepatic transaminases (19%; all recovered without sequelae), pneumonia (17%), stomatitis (14%), hyperglycemia (13%), and sepsis (11%). No myelosuppression requiring dose modification or evidence of tumor lysis syndrome was seen. In Part A, single agent antileukemic activity was documented with a best response of CR (2) or CRi (1) in 3/13 AML patients (CR/CRi rate 23%) treated at the two highest dose levels studied to date (1.3 and 2.3 µg/kg weekly); no CR, CRi, or morphologic leukemia-free state (MLFS) responses were seen at lower doses. Antileukemic activity occurred quickly; all responders had achieved at least an MLFS response after 4 doses (1 cycle). Two responders were bridged to stem cell transplantation, and the third was ineligible for medical reasons but remains in remission at 14+ weeks after initiating therapy.Conclusions: XmAb14045 demonstrated evidence of antileukemic activity in heavily pretreated patients with relapsed/refractory AML treated in Part A at the 1.3 and 2.3 µg/kg doses administered once weekly, with a 23% CR/CRi rate. CRS was the most common toxicity but was generally manageable with premedications. The study is ongoing with further optimization of dose, schedule, and premedication regimen for CRS anticipated during accrual to dose escalation cohorts in Part B.ClinicalTrials.gov Identifier: NCT02730312 DisclosuresRavandi:Xencor: Research Funding; Abbvie: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Sunesis: Honoraria; Astellas Pharmaceuticals: Consultancy, Honoraria; Abbvie: Research Funding; Seattle Genetics: Research Funding; Macrogenix: Honoraria, Research Funding; Jazz: Honoraria; Sunesis: Honoraria; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Orsenix: Honoraria; Xencor: Research Funding; Orsenix: Honoraria; Jazz: Honoraria; Bristol-Myers Squibb: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Macrogenix: Honoraria, Research Funding. Foran:Xencor, Inc.: Research Funding; Agios: Research Funding. Stock:Jazz Pharmaceuticals: Consultancy. Mawad:Swedish Cancer Institute: Employment. Blum:Astellas: Consultancy; Pfizer: Consultancy; Boehringer Ingelheim: Research Funding; Forma: Research Funding; Xencor: Research Funding; Tolero: Research Funding. Saville:Xencor, Inc.: Employment, Equity Ownership. Johnson:Xencor, Inc.: Employment, Equity Ownership. Vanasse:Novartis: Employment, Equity Ownership. Ly:Xencor, Inc.: Employment, Equity Ownership. Mims:Novartis: Consultancy; Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

Prevalence of central and peripheral neuropathic pain in patients attending pain clinics in Spain: factors related to intensity of pain and quality of life.

BackgroundThe objective of the study was to estimate the prevalence of pure central neuropathic pain (CNP) and peripheral neuropathic pain (PNP) among patients attending pain clinics in Spain. The study also aimed to analyze factors associated with pain intensity and quality of life (QoL).MethodsA cross-sectional study was performed including 53 patients with pure CNP and 281 with pure PNP attending in 104 pain clinics in Spain. The revised grading system proposed in 2008 to determine a definite, probable or possible diagnosis of NP was used. Pain features, psychological variables and QoL were assessed. Descriptive, bivariate and multivariate analyses were performed.ResultsThe prevalence of pure CNP and PNP amongst neuropathic pain patients was 2.4% (95% CI: 1.7;3.1) and 12.9% (95% CI: 1.5;14.3), respectively. Comorbid anxiety, depression or sleep disorders were high in both groups, but higher in CNP patients (51.1%, 71.4%, respectively). Pain intensity in PNP patients was associated with the presence of depression and sleep disturbances. However, in CNP patients, it was related with pain in the lower limbs. The impairment of QoL was greater in CNP patients than in PNP patients; pain location, presence of depression and sleep disturbance were the factors that most negatively affected QoL. Among PNP patients, women and those with higher pain intensity had worse QoL.ConclusionPain intensity and QoL are affected by different factors in patients suffering from CNP or PNP. Identifying these factors could serve to guide therapeutic strategies and improve the QoL of patients.

Abstract P1-06-04: Simplified histological grading of breast carcinoma – potential for improved concordance and consistency in breast cancer grading?

Abstract Histological grade remains an independent predictor of outcome for invasive breast cancer. The internationally accepted standard grading system is the Elston and Ellis grading system based on a local hospital (Nottingham) cohort treated between 1951-1973. Histological grade, with nodal status, tumour size and receptor measurements (ER, PgR, HER2) give important information even in the context of current molecular testing for breast cancer. In 2009 we proposed a simplified approach to the EE system based on evidence from another hospital series (Thomas et al Histopathology 2009 DOI 10.1111/j.1365-2559.2009.03429.x). Here we report a second validation of this approach using a large phase III clinical trial cohort the Tamoxifen Exemestane Adjuvant multicentre Trial. A single pathologist (EM) regraded over 4200 cases using a single H&amp;E slide from the TEAM pathology study. Individual scores (1-3) were provided for tubule formation, nuclear pleomorphism and mitotic count and summed to provide the EE score (3-9) resulting in a final grade of 1, 2 or 3 for each case. As previously reported the Simplified Binary Scoring system (SBS) reorganizes this data such that each component is given a score of 1 or 2 with a sum ranging from 3-6. In the current analysis we compared the impact of this revised grading system on patient outcome. Of 4264 centrally regraded tumours in the TEAM pathology cohort, EE scores for tubular formation were 1 in 102 cases (2.4%), 2 in 503 cases (11.8%) and 3 in 3659 (85.8%). For nuclear pleomorphism only 2 cases were EE score 1 (0.05%), 3117 were score 2 (73.1%) and 1146 score 3 (26.9%). For Mitotic count 3423 (80.3%) were scored 1, 707 (16.6%) scored 2 and 134 scored 3 using the EE system. As previously observed, most/all EE categories could be captured using a simple binary system (SBS, see Table 1). Table 1 EE Grade SBS SCORE12335460043239705068217600618 GG Score EE GradeLowHigh 13327819.02%21377132248.98%35751790.07% GG Score SBS SCORELowHigh 33508419.35%4120284741.34%515947474.88%65751289.98% In a comparison between conventional grading and molecular (using a Genomic-Grade signature) we observed the predicted equal split of EE Grade 2 cases into GG high/versus low. For the SBS score the higher scores were enriched for GG High cases. We show a novel grading system can provides a potentially simple and more reproducible approach to immunohistochemical grading. Comparisons with molecular grading approaches may suggest improved concordance between novel grading approaches and molecular systems. Further comparisons with outcome and molecular signatures will be presented. Citation Format: Bartlett JMS, Thomas J, Mallon E, Piper T, Bayani J, Hasenburg A, Kieback DG, Markopoulos C, Dirix L, Seynaeve C, van de Velde CJH, Rea DW. Simplified histological grading of breast carcinoma – potential for improved concordance and consistency in breast cancer grading? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-06-04.

Revised grading system of tympanosclerosis

IntroductionTympanosclerosis (TS) is a common sequelae of chronic otitis media found in all age groups, this study was conducted to analyze the extent of tympanosclerosis in patients operated for chronic suppurative otitis media in our hospital and have intraoperative findings of tympanosclerosis. Material and method165 patients of tympanoplasty who had TS involving ossicular chain, were enrolled in our study. Pre operative air bone gap and operative findings of extent of TS involving ossicles was recorded, time required to mobilize ossicles was also recorded. Post operative air bone gap was documented after 3months of surgery. ResultThis study showed that majority of patients were females from rural area. Most of the patients had grade II tympanosclerosis followed by grade III. There was no statistically significant difference in post operative air bone gap in patients with grade I and grade II TS. Our new grading system for TS removes the overlap between various grading systems for TS developed in past. ConclusionNew grading system for TS helps us to determine time taken for mobilizing ossicular chain, type of ossiculoplasty required and outcome of tympanoplasty surgery.

The intra-rater reliability of a revised 3-point grading system for accessory joint mobilizations

Objectives: Joint mobilizations are often quantified using a 4-point grading system based on the physiotherapist’s detection of resistance. It is suggested that the initial resistance to joint mobilizations is imperceptible to physiotherapists, but that at some point through range becomes perceptible, a point termed R1. Grades of mobilization traditionally hinge around this concept and are performed either before or after R1. Physiotherapists, however, show poor reliability in applying grades of mobilization. The definition of R1 is ambiguous and dependent on the skills of the individual physiotherapist. The aim of this study is to test a revised grading system where R1 is considered at the beginning of range, and the entire range, as perceived by the physiotherapists maximum force application, is divided into three, creating 3 grades of mobilization.Method: Thirty-two post-registration physiotherapists and nineteen pre-registration students assessed end of range (point R2) and then applied 3 grades of AP mobilizations, over the talus, in an asymptomatic models ankle. Vertical forces were recorded through a force platform. Intra-class Correlation Coefficients, Standard Error of Measurement, and Minimal Detectable Change were calculated to explore intra-rater reliability on intra-day and inter-day testing. T-tests determined group differences.Results: Intra-rater reliability was excellent for intra-day testing (ICC 0.96–0.97), and inter-day testing (ICC 0.85–0.93). No statistical difference was found between pre- and post-registration groups.Discussion: Standardizing the definition of grades of mobilization, by moving R1 to the beginning of range and separating grades into thirds, results in excellent intra-rater reliability on intra-day and inter-day tests.Level of Evidence: 3b.

Neuropathic pain: an updated grading system for research and clinical practice.

The redefinition of neuropathic pain as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system,” which was suggested by the International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) in 2008, has been widely accepted. In contrast, the proposed grading system of possible, probable, and definite neuropathic pain from 2008 has been used to a lesser extent. Here, we report a citation analysis of the original NeuPSIG grading paper of 2008, followed by an analysis of its use by an expert panel and recommendations for an improved grading system. As of February, 2015, 608 eligible articles in Scopus cited the paper, 414 of which cited the neuropathic pain definition. Of 220 clinical studies citing the paper, 56 had used the grading system. The percentage using the grading system increased from 5% in 2009 to 30% in 2014. Obstacles to a wider use of the grading system were identified, including (1) questions about the relative significance of confirmatory tests, (2) the role of screening tools, and (3) uncertainties about what is considered a neuroanatomically plausible pain distribution. Here, we present a revised grading system with an adjusted order, better reflecting clinical practice, improvements in the specifications, and a word of caution that even the “definite” level of neuropathic pain does not always indicate causality. In addition, we add a table illustrating the area of pain and sensory abnormalities in common neuropathic pain conditions and propose areas for further research.