Medical Research Council Classification Research Articles

Multichannel Conduits with Fascicular Complementation: Significance in Long Segmental Peripheral Nerve Injury.

Despite the advances in tissue engineering approaches, reconstruction of long segmental peripheral nerve defects remains unsatisfactory. Although autologous grafts with proper fascicular complementation have shown meaningful functional recovery according to the Medical Research Council Classification (MRCC), the lack of donor nerve for such larger defect sizes (>30 mm) has been a serious clinical issue. Further clinical use of hollow nerve conduits is limited to bridging smaller segmental defects of denuded nerve ends (<30 mm). Recently, bioinspired multichannel nerve guidance conduits (NGCs) gained attention as autograft substitutes as they mimic the fascicular connective tissue microarchitecture in promoting aligned axonal outgrowth with desirable innervation for complete sensory and motor function restoration. This review outlines the hierarchical organization of nerve bundles and their significance in the sensory and motor functions of peripheral nerves. This review also emphasizes the major challenges in addressing the longer nerve defects with the role of fascicular arrangement in the multichannel nerve guidance conduits and the need for fascicular matching to accomplish complete functional restoration, especially in treating long segmental nerve defects. Further, currently available fabrication strategies in developing multichannel nerve conduits and their inconsistency in existing preclinical outcomes captured in this review would seed a new process in designing an ideal larger nerve conduit for peripheral nerve repair.

Polyethylene Glycol-Mediated Axonal Fusion Promotes Early Sensory Recovery After Digital Nerve Injury: A Randomized Clinical Trial

Background. Peripheral nerve repair is limited by Wallerian degeneration coupled with the slow and inconsistent rates of nerve regrowth. In more proximal injuries, delayed nerve regeneration can cause debilitating muscle atrophy. Topical application of polyethylene glycol (PEG) during neurorrhaphy facilitates the fusion of severed axonal membranes, immediately restoring action potentials across the coaptation site. In preclinical animal models, PEG-fusion resulted in remarkable early functional recovery. Methods. This is the first randomized clinical trial comparing functional outcomes between PEG-fusion and standard neurorrhaphy. Participants with digital nerve transections were followed up at 2 weeks, 1 month, and 3 months postoperatively. The primary outcome was assessed using the Medical Research Council Classification (MRCC) rating for sensory recovery at each timepoint. Semmes-Weinstein monofilaments and static two-point discrimination determined MRCC ratings. Postoperative quality of life was measured using the Michigan Hand Questionnaire (MHQ). Results. Forty-eight transected digital nerves (25 control, 23 PEG) across twenty-two patients were analyzed. PEG-fused nerves demonstrated significantly higher MRCC scores at 2 weeks (OR 16.95, 95% CI: 1.79 – 160.38, p = 0.008) and 1 month (OR 13.40, 95% CI: 1.64 – 109.77, p = 0.009). Participants in the PEG cohort also had significantly higher average MHQ scores at 2 weeks (Hodge’s g 1.28, 95% CI: 0.23 – 2.30, p = 0.0163) and 1 month (Hodge’s g 1.02, 95% CI: 0.04 – 1.99, p = 0.049). No participants had adverse events related to the study drug. Conclusion. PEG-fusion promotes early sensory recovery and improved patient well-being following peripheral nerve repair of digital nerves.

[Efficacy and Safety of Decitabine Combined with Modified CAG Regimen in Patients Aged ≥ 70 Years with Newly Diagnosed Acute Myeloid Leukemia].

To evaluate the clinical efficacy and safety of decitabine combined with modified CAG regimen (D-CAG regimen) in patients aged ≥70 years with newly diagnosed acute myeloid leukemia (AML). The clinical data of 59 AML patients (≥70 years old) who were newly diagnosed and treated in the Hematology Department of the First Affiliated Hospital of Nanjing Medical University from November 2010 to June 2021 were retrospectively analyzed. Among the 59 AML patients, 28 were males and 31 were females, with a median age of 74 (70-86) years. The complete remission (CR) rate was 69.4% (34/49), and the median duration of CR was 10.7 (0.6-125.4) months after 2 courses of D-CAG treatment. According to the British Medical Research Council (MRC) classification, there was only one patient in the favorable-risk group, and the CR rate was 71.8% (28/39) in the intermediate-risk group, and 55.6% (5/9) in the adverse-risk group, respectively. There was no statistical difference in the CR rate between the intermediate-risk and adverse-risk group. Referring to ELN 2017 genetic risk classification, CR rate was 88.2% (15/17) in the favorable-risk group, 45.5% (5/11) in the intermediate-risk group, and 66.7% (14/21) in the adverse-risk group. There was no significant difference in CR rate between the favorable-risk and adverse-risk categories, but both were significantly higher than that in the intermediate-risk group (P <0.05). Next-generation sequencing (NGS) analysis showed that 11 gene mutations with a frequency of more than 10%, including TET2 mutation (35.6%), ASXL1 mutation (30.5%), NPM1 mutation (28.8%), FLT3-ITD mutation (27.1%), DNMT3A mutation (22.0%), IDH1 mutation (15.3%), CEBPA single mutation (13.6%), TP53 mutation (13.6%), IDH2 mutation (11.9%), RUNX1 mutation (11.9%), and NRAS mutation (10.2%). There were no statistical differences in mutation frequency of these 11 genes between CR group and non-CR group. Compared with normal karyotypes, patients with complex karyotypes were more likely to develop TP53 mutations (P <0.001), while FLT3-ITD and DNMT3A mutations were more likely to occur in patients with normal karyotypes (P =0.04, P =0.047). The median follow-up, overall survival (OS), and event-free survival (EFS) of all the patients was 11.7 (1.5-128.2) months, 12.3 (1.5-128.2) months, and 8.5 (1.5-128.2) months, respectively. The median OS and EFS of CR patients were 19.8 and 13.3 months, respectively, which were significantly longer than 6.4 and 5.7 months in patients experiencing treatment failure (P < 0.001, P =0.009). In regard to genes with mutation frequency >10%, there were no statistical differences in CR rate, median OS, and median EFS between mutated and wild-type patients by Chi-square test and survival analysis. Univariate analysis showed that age, hemoglobin, lactate dehydrogenase, cytogenetics and CR were factors affecting prognosis, while multivariate analysis showed that only CR failure was an independent adverse prognostic factor for OS. The major adverse reactions to D-CAG regimen were grade 3-4 myelosuppression, pulmonary infection, and fever (infection focus was not identified). D-CAG regimen is safe and effective in the treatment of AML patients ≥70 years old, and can partially improve the prognosis of elderly and high-risk patients.

Allogeneic Hematopoietic Cell Transplantation vs Standard Consolidation Chemotherapy in Patients With Intermediate-Risk Acute Myeloid Leukemia

The ideal postremission strategy in intermediate-risk acute myeloid leukemia (AML) in first complete remission (CR) has been a matter of debate. To explore the optimal therapy for patients with intermediate-risk AML after first complete remission. This investigator-initiated, open-label, 2-armed, phase 3 randomized clinical trial assessed patients at 16 hospitals in Germany from February 2, 2011, until July 1, 2018. Key eligibility criteria included cytogenetically defined intermediate-risk AML according to Medical Research Council classification, first CR or CR with incomplete blood cell count recovery after conventional induction therapy, age of 18 to 60 years, and availability of a human leukocyte antigen (HLA)-matched sibling or unrelated donor. A detailed statistical analysis plan was written and finalized on July 7, 2020. Data were exported for analysis on April 13, 2021. Patients were randomized 1:1 to receive allogeneic hematopoietic cell transplantation (HCT) or high-dose cytarabine for consolidation and salvage HCT only in case of relapse. Strata for randomization included age (18-40 vs 41-60 years), NPM1 and CEBPA variation status, and donor type (unrelated vs related). End points included overall-survival as the primary outcome and disease-free survival, cumulative incidence of relapse, treatment-related mortality, and quality of life measured according to the Medical Outcomes Study 36-Item Short-Form Health Survey as secondary outcomes. A total of 143 patients (mean [SD] age, 48.2 [9.8] years; 81 [57%] male) with AML who fulfilled the eligibility criteria were randomized. In the intention-to-treat analysis, the probability of survival at 2 years was 74% (95% CI, 62%-83%) after primary allogeneic HCT and 84% (95% CI, 73%-92%) after consolidation chemotherapy (P = .22). Disease-free survival after HCT at 2 years was 69% (95% CI, 57%-80%) compared with 40% (95% CI, 28%-53%) after consolidation chemotherapy (P = .001). Allogeneic HCT during the first CR was associated with a cumulative incidence of relapse at 2 years of 20% (95% CI, 13%-31%) compared with 58% (95% CI, 47%-71%; P < .001). Nonrelapse mortality at 2 years after primary allogeneic HCT was 9% (95% CI, 5%-19%) and 2% (95% CI, 0%-11%) after consolidation chemotherapy (P = .005). Similar outcomes were observed when analyses were confined to the 96 patients at intermediate risk according to the European Leukemia Network classification. Most importantly, all 41 patients relapsing after consolidation chemotherapy (36 hematologic, 4 molecular, and 1 extramedullary) proceeded to allogeneic HCT. No significant differences in health-related quality of life measures were observed between groups. Primary allogeneic HCT during first CR was not associated with superior overall survival compared with consolidation chemotherapy in patients 60 years or younger with intermediate-risk AML during the first CR and an available donor. ClinicalTrials.gov Identifier: NCT01246752.

P504: CLINICAL MUTATIONAL ANALYSIS BY NEXT-GENERATION SEQUENCING AND REAL-LIFE VALIDATION OF THE REVISED 2017 EUROPEAN LEUKEMIANET GENETIC RISK STRATIFICATION IN AML PATIENTS

Background: Recently, a census of mutated genes in AML has been described but their value in clinical practice is not fully elucidated. The revised 2017 European LeukemiaNet (ELN) recommendations for genetic risk stratification of AML have been widely adopted, but have not yet been validated in large cohorts of AML patients in real life. Aims: The objective of this work is to analyze the mutations detected by Next Generation Sequencing (NGS) and to study whether the application of ELN 2017 scale improves prognostic risk stratification with respect to ELN 2010 and Medical Research Council (MRC). Methods: We included 112 adult AML patients diagnosed in our center between Jun2017 and Dec2021 and who were studied at diagnostic using the spanish PLATFOLMA PETHEMA. The prognostic risk was established according to MRC, ELN2010 and ELN2017 classification. Baseline demographic, disease characteristics, treatment procedures and mutations by functional groupsare summarized in Table 1 NPM1 and FLT3-ITD were determined by melting curve analysis and standard PCR-EC technique according to Thiede et al (Blood 2002) in ABI 3130 Analyzer (Thermofisher). For NGS, the commercial panel Myeloid SolutionTM (Sophia Genetics) KAPA Kit amplification libraries and sequencing on ILUMINA Myseq platform were used. Variant analysis was performed using DDM software (Sophia Genetics). Results: The majority of the patients (97.1%) had at least one mutation at diagnosis detected by NGS. The median number of mutations was 2.36 (0-6). Grouped by functional groups, the most frequent were those related to DNA methylation (44.6 %) and signaling/kinase pathways (37.5%). The most prevalent were FLT3 (29 %), IDH1/IDH2 (27%) and TP 53 (19.6%) followed by NPM1 and RUNX-1 (17%). Patients older than 60 years, presented higher percentage of unfavorable ASXL1 (18.6%), RUNX1 (20%) and TP53 (25.7%) mutations with respect to younger (4.8%, 11.9% and 9.5 %) being these differences statistically significant in ASXL 1 and TP 53 (χ2 p=0.044 and p=0.047 respectively). NPM1 (28.6%) and FLT3 (40.5%) mutations were significantly more frequent in younger patients (χ2 p=0.017 and p=0.013 respectively), than in >60 years (10% and 17.1%, respectively). Re-stratifying according to ELN 2017, the 53% of patients categorized within the intermediate risk group according to MRC change prognostic group: 28.9% became redefined as unfavorable risk and 24.1% as favorable. In the overall series the overall survival analysis shows statistically significant differences taking into account either ELN 2017 or ELN 2010 and MRC (T.logrank p=0.003, p=0.018 and p=0.012, respectively). However, according to ELN 2017 there are greater differences between intermediate and unfavorable groups than in the other classifications. Statistically significant differences in overall survival according to ELN 2017 (T.logrank p=0.028) are also found in patients receiving intensive treatment. The estimated overall survival at two years is 72.%, 52.1% and 46.8% in the favorable, intermediate and unfavorable group, respectively. Image:Summary/Conclusion: - NGS proves its usefulness by detecting more clinically relevant alterations than conventional cytogenetic techniques and PCR, and stratifies a larger group of patients as favorable and unfavorable. - Our results validate the prognostic significance of the ELN2017 classification in real life, both in the overall series and in candidates for intensive QT. - ELN 2017 establishes greater survival differences between the intermediate and unfavorable group than ELN 2010 and MRC redefining the intermediate group.

Challenges and Controversies in the Management of Tuberculous Meningitis with Hydrocephalus: A Systematic Review and Sarawak Institution's Experience.

Introduction  To date, there are no standard practice guidelines available and no universal consensus regarding treatment protocol in management of tuberculous meningitis (TBM) with hydrocephalus. Over the years, diverse views have existed in neurosurgical management of TBM with hydrocephalus. Some authors advocate ventriculo-peritoneal (VP) shunt, while others suggest that external ventricular drainage (EVD) may be the preferable neurosurgical procedure for a poor-grade patient. Method  We systematically reviewed published literature and presented our institution's experience. We performed a retrospective case study in our Sarawak neurosurgical center from 2018 to 2020. We tabulated the outcome according to preoperative classifications, which were Vellore Grading (VG), Modified Vellore Grading (MVG), British Medical Research Council Classification (MRC), and others: author-defined. Result  In our center, there were 20 cases of TBM with hydrocephalus treated by EVD and VP shunt from 2018 to 2020. We systematically searched published medical literature, and 23 articles were retrieved and analyzed. Poor outcomes were observed in poor-grade patients, especially VG/MVG 3/4 and MRC 3, from both institution and systemic review data. Shunt complication rate was lower in our center as compared with published literature. Conclusion  Unfortunately, morbidity and mortality were approximately twofold higher in poor-grade as compared with good-grade patients. However, about one-third of poor-grade patients achieved a good outcome. Cerebrospinal fluid (CSF) diversion would be an unavoidable treatment for hydrocephalus. Poor-grade patients tend to have cerebral infarcts in addition to hydrocephalus. An extended duration of EVD placement could be a potential measure to assess Glasgow coma scale recovery and monitor serial CSF samples.

COMMON PERONEAL NERVE INJURIES AT THE KNEE: OUTCOMES OF NERVE REPAIR

Background. Common peroneal nerve (CPn) lesion at the knee is one of the most frequent neurologic injury of the lower limb. Among the etiologies there are also open and closed trauma. If direct nerve repair is not possible, nerve grafting is indicated as a primary or delayed procedure. Nerve and tendon transfer are other possible therapeutic options. Material and methods. In this retrospective double center study, 35 patients with post-traumatic CPn lesion at the knee, that underwent surgical repair, were analyzed. Exclusion criteria were severe concomitant neurological pathologies, complex injury of the lower leg including major vessels lesion and or tibial nerve injury. The objective of the study is to demonstrate the degree of foot dorsiflexion recovery based on the type of trauma and the corresponding performed surgery: the Medical Research Council classification (M0-M5) was used as rating scale. Results. There were 23 closed and 12 open injuries. Time of surgery varied from 6 to 11 months after closed trauma, whereas 2 open traumas were explored at emergency and the remaining 10 patients were explored 3 to 9 months after injury. Neurolysis was performed in 12 cases. Neurorraphy was performed in 2 cases. Sural nerve grafting was performed in 21 patients, with a length range of 6-10,5 cm and 4-9 cm for closed and open trauma respectively. Conclusions. Our series confirms that repairs of traumatic CPn injuries have an unfavorable outcome. Motor recovery score ≥&nbsp;M3 was obtained in only 10 cases (28,57%). Neurolysis and nerve suture show better results than nerve graft alone, although no statistically significant differences emerged; CPn reconstructions with grafts show unsatisfactory results, particularly if the length of the grafts exceeds 6 cm and when patients are treated over 6 months after the trauma. Patients with closed trauma achieve less satisfactory results than those with open injury (13 vs 58%) and this was statistically significant (p&nbsp;&lt;&nbsp;0.05), so palliative surgery may be indicated as the first surgical approach for these patients to achieve good foot dorsiflexion.

Failed Acellular Nerve Allografts: A Critical Review.

Acellular nerve allograft (ANA) occupies an increasingly prominent role in the treatment of peripheral nerve reconstruction. There is demonstrable efficacy; however, some grafts fail to support axonal regrowth and the reasons for this are unclear. This study examines the ANA experience in a specialized peripheral nerve surgery department to discuss the clinical and histological findings in failed cases. Failed ANA grafts were identified from a prospective database using Medical Research Council Classification (MRCC) S3 and M3 as thresholds for success. Cases in which ANA grafting was indicated for nerve related pain and dysesthesia but where no subjective improvement in symptoms occurred were also included. Patients requiring revision surgery after ANA grafting were also considered failures. Cases were then examined in conjunction with a literature review to identify possible mechanisms of failure, including detailed histological analysis in 2 cases. Eight failed procedures were identified from a database of 99 separate allograft records on 74 patients. This included procedures for 2 tibial nerves, 2 superficial radial nerves, 2 median nerves, 1 digital nerve and a lateral cord brachial plexus injury (male/female, 5:3; age range, 24-54 years). Allograft length range 25 to 120 mm. One postoperative infection was identified. Histological findings in 2 cases included adequate vascularization of allograft material without subsequent axonal regeneration, a reduction of large myelinated fibers proximal to a tibial nerve allograft in the setting of a chronic injury, and a preference for small rather than large fiber regeneration. This article reports instances of ANA graft failure in a variety of contexts, for which the primary reasons for failure remain unclear. The etiology is likely to be multifactorial with both patient, graft and surgeon factors contributing to failure. Further clinical and histological analysis of ANA failures will improve our understanding of the mechanisms of graft failure.

Early Bone Marrow Assessment after 7+3 Induction Chemotherapy Is Predictable of Outcome in AML with Adverse Cytogenetics

IntroductionAlthough many new therapeutic agents have been introduced in the field of AML, the most important intensive induction regimen of AML patients is still 7+3 chemotherapy based on cytarabine and anthracycline. Currently, major guidelines recommend to exam bone marrow (BM) assessment in 14-21 days after the initiation of induction to determine whether to proceed with intensification chemotherapy. However, there is no solid evidence that these timings are most optimal. If the evaluation at an earlier time point is prognostic for response, earlier intensification could be considered. In this regard, we investigated if the BM blast rate at the 7th day after the start of 7+3 chemotherapy (D7 BM blast) was useful in predicting the treatment response of induction chemotherapy.MethodsWe retrospectively collected the data of patients who were newly diagnosed with AML from February 2002 to February 2021, received induction chemotherapy by 7+3, had a D7 BM examination without any intensification. A total of 665 patients were enrolled and we analyzed the prognostic significance of the D7 BM blast for the induction treatment response (complete remission or complete remission with incomplete hematologic recovery (CR/CRi)). In addition, we analyzed whether the predictive significance of the D7 BM blast varies by the patient's cytogenetic features by Medical Research Council classification (MRC risk). Then, we evaluated the diagnostic ability of the D7 BM blast by the receiver operating characteristic (ROC) curve for treatment response prediction. To find an optimal D7 BM blast cut-off value, the value that maximizes Youden's index was investigated.ResultsAmong 665 AML patients who underwent 7+3 without intensification, the proportion of patients who acquired CR/CRi after single induction was 68.3%. A significant decrease in the CR/CRi rate was observed in the intermediate/adverse MRC group according to the increase of the D7 BM blast (tests for the trends in the intermediate and adverse group, p<0.001 and p=0.008, respectively; Figure 1). In univariable/multivariable (using covariates of age, sex, etiology, and MRC risk) logistic regression models, the D7 BM blast showed a significant correlation with the CR/CRi rate in the intermediate/adverse cytogenetic group (Table 1). To evaluate the usability of the D7 BM blast as a predictive tool, the ROC curve for the treatment response prediction was plotted (Figure 2) and the D7 BM blast was significantly predictable only in the adverse MRC risk group (Area under the curve: 0.7007, Mann-Whitney test statistics p=0.002). The D7 blast cut-off in the adverse MRC risk group which maximizes Youden's index was 4-4.9%, near to 5%, which is the cut-off used to evaluate the treatment response. The sensitivity and specificity for treatment response prediction according to D7 BM blast <5% or not were 82.8% and 61.1%, respectively.ConclusionThe BM assessment performed at 7 days after 7+3 chemotherapy was available to predict the treatment response in intermediate and adverse cytogenetic risk patients. In particular, it can be practically used in patients with adverse cytogenetics, and a value of around BM blast 5% can be used as cut-off for response prediction. Early intensification in these patients could be considered, which would be beneficial in various aspects such as shorter nadir period or hospital stay and possibly better treatment response compared with the current strategies of later intensification or second induction. [Display omitted] DisclosuresKim: Novartis: Research Funding; BMS: Research Funding; Pfizer: Research Funding; ILYANG: Research Funding; Takeda: Research Funding. Lee: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kim: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AIMS Biosciense: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AML-Hub: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BL & H: Research Funding; BMS & Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boryung Pharm Co.: Consultancy; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Consultancy, Honoraria; LG Chem: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Pintherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Honoraria, Speakers Bureau; SL VaxiGen: Consultancy, Honoraria; VigenCell: Consultancy, Honoraria.

Long-Term Outcome of Peripheral Blood Autologous Stem Cell Transplantation (AutoSCT) for De Novo Acute Myeloid Leukemia in Patients Achieving First Complete Remission after One Vs Two Induction Courses: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Background: Achieving a first complete remission (CR1) is the primary goal in the treatment of AML and is an important prognostic factor for transplantation outcome in general and even more so for autologous transplantation (AutoSCT). However, there are no data for AutoSCT indicating whether the number of chemotherapy courses (1 vs 2) needed to achieve CR1 is of prognostic significance for transplantation outcome.Methods: Using the EBMT/ALWP registry, we compared transplantation outcomes of adult patients (pts) aged ≥18 years with de novo AML that underwent a peripheral blood AutoSCT in 2000-2019 in CR1 achieved following one vs two chemotherapy courses. The primary outcome was the Leukemia Free Survival (LFS). Multivariate analysis (MVA) adjusting for differences between the groups and knowns factors were performed using Cox's proportional- hazards regression model for outcomes.Results: 1825 pts were included: 1532 (84%) with one and 293 (16%) with two induction chemotherapies courses. Time from diagnosis to AutoSCT was 4.7 (3.9-5.8) vs 5.7 (4.7-7.1) months, respectively (p<0.001). Median follow-up was 7.9 (95% CI: 7.4-8.4) and 7.7 (95% CI: 7.0-8.6) years, respectively (p=0.8). Median year of transplant was 2005 (2002-2009) and 2004 (2002-2007), respectively (p<0.001). Median age was 49 (38-57) and 47 (36 -56) years (p=0.06); 54% and 57 % of both groups were male, (p=0.35). Cytogenetic risk as defined by the Medical Research Council (MRC) classification, differed significantly between the two induction groups (p<0.001). Patients with one induction had a higher percentage of favorable-risk than those with two inductions (18% vs 14%), and a lower percentage of adverse-risk cytogenetics (6% vs 13%), while 76% and 73%, respectively, had intermediate-risk cytogenetics (missing data-11percentage). Karnofsky performance score (KPS) > 90 was higher in pts receiving 1 vs 2 inductions, 71% and 58% of pts, respectively (p<0.001). The most frequent conditioning regimen for both groups was Busulfan (Bu) /Cytoxan (Cy) 50% vs 45% and Bu / Melphalan (Mel) 17% and 19%, respectively, for induction groups 1 and 2, respectively.Day 30 neutrophil engraftment incidence was 96% and 96.5%.Five -year non-relapse mortality (NRM) was 6.2% vs 6.0% for pts achieving CR1 with 2 vs 1 chemotherapy courses, respectively, and did not differ significantly (HR=1.31 (95% CI: 0.81-2.10), p=0.27). Five -year relapse incidence (RI) was higher :67.2% vs 52.3%, (HR=1.46 (95% CI: 1.25-1.72), p<0.001), while LFS and overall survival (OS) were lower for pts achieving CR1 with 2 vs 1 course of chemotherapy: 26.6% vs 41.7% (HR= 1.42 (95% CI: 1.22-1.66), p<0.001) and 36.2% vs 53.3%, (HR=1.48 (95% CI: 1.25-1.75), p<0.001), respectively (Figure). Other significant prognostic factors in MVA were adverse- compared to good risk cytogenetics and older age (per 10 years) for all AutoSCT outcome parameters including RI, NRM, LFS and OS; intermediate compared to good risk cytogenetics for RI, LFS and OS; female gender for RI and LFS ;and year of transplant for RI and OS.Conclusions: The five -year RI was higher and transplantation outcomes significantly inferior in pts with AML undergoing AutoSCT but who received two lines of chemotherapy to achieve CR1. Such pts may benefit from additional novel therapies in the conditioning or post-AutoSCT or be considered for allogeneic transplantation in an attempt to reduce their high RI and improve outcomes. [Display omitted] DisclosuresLabopin: Jazz Pharmaceuticals: Honoraria. Blaise: Jazz Pharmaceuticals: Honoraria. Huynh: Jazz Pharmaceuticals: Honoraria. Mohty: Takeda: Honoraria; Jazz: Honoraria, Research Funding; Astellas: Honoraria; Janssen: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Gilead: Honoraria; Pfizer: Honoraria; Adaptive Biotechnologies: Honoraria; Sanofi: Honoraria, Research Funding. Pigneux: Amgen: Consultancy; Sunesis: Consultancy, Research Funding; BMS Celgene: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.

Clinical Outcomes of Symptomatic Neuroma Resection and Reconstruction with Processed Nerve Allograft

Background:Neuromas causing sensory disturbance can substantially affect nerve function and quality of life. Historically, passive termination of the nerve end and proximal relocation to muscle or bone has been performed after neuroma resection, but this method does not allow for neurologic recovery or prevent recurrent neuromas. The use of processed nerve allografts (PNAs) for intercalary reconstruction of nerve defects following neuroma resection is reasonable for neuroma management, although reported outcomes are limited. The purpose of this study was to assess the outcomes of pain reduction and functional recovery following neuroma resection and intercalary nerve reconstruction using PNA.Methods:Data on outcomes of PNA use for peripheral nerve reconstruction were collected from a multicenter registry study. The registry database was queried for upper extremity nerve reconstruction with PNA after resection of symptomatic neuroma. Patients completing both pain and quantitative sensory assessments were included in the analysis. Improvement in pain-related symptoms was determined via patient self-reported outcomes and/or the visual analog scale. Meaningful sensory recovery was defined as a score of at least S3 on the Medical Research Council Classification scale.Results:Twenty-five repairs involving 21 patients were included in this study. The median interval from injury to reconstruction was 386 days, and the average nerve defect length was 31 mm. Pain improved in 80% of repairs. Meaningful sensory recovery was achieved in 88% of repairs.Conclusion:Neuroma resection and nerve reconstruction using PNA can reduce or eliminate chronic peripheral nerve pain and provide meaningful sensory recovery.

[Risk assessment of intensive care unit admission for postoperative patients with stable chronic obstructive pulmonary disease].

To observe the risk factors of intensive care unit (ICU) admission for postoperative patients with stable chronic obstructive pulmonary disease (COPD). Patients with stable COPD who were admitted to Shengjing Hospital of China Medical University for proposed surgical procedures from March 2014 to December 2020 were enrolled. Based on the criteria of the global initiative for chronic obstructive lung disease (GOLD), the patients were classified according to the severity of airflow limitation as grade 1 [forced expiratory volume in one second as a percentage of expected value (FEV1%) ≥ 80%], grade 2 (50% ≤ FEV1% < 80%), grade 3 (30% ≤ FEV1% < 50%), and grade 4 (FEV1% < 30%). Then the patients were divided into groups A, B, C, D according to symptom level and history of moderate/severe acute exacerbation within 1 year. The patients in the group A had the lightest symptoms, the lowest frequency and degree of acute exacerbation, while those in the group D had the most severe symptoms, the most frequent and degree of acute exacerbation. Data of general information, COPD-related factors, surgical-related factors and postoperative admission to ICU were collected. The correlation between different degree of airflow limitation subgroups as well as different comprehensive assessment of symptom subgroups and risk of postoperative ICU admission was analyzed. Multivariate Logistic regression models were used to analyze the risk factors affecting postoperative ICU admission. A total of 143 patients were enrolled in the analysis. According to the degree of airflow limitation, there were 34 patients in GOLD grade 1, 72 in grade 2, 32 in grade 3 and 5 in grade 4. According to the comprehensive assessment of symptoms, there were 78 patients in group A, 31 in group B, 5 in group C and 29 in group D. There were no statistically significant differences in the general data of gender, age, height and weight of patients in each group with different degrees of airflow limitation and different comprehensive assessment of symptoms. Univariate analysis showed that the degree of airflow limitation and comprehensive assessment of symptoms were not associated with postoperative ICU admission [degree of airflow limitation: odds ratio (OR) = 1.526, 95% confidence interval (95%CI) was 0.682-3.415, P = 0.304; comprehensive assessment of symptoms: OR = 1.508, 95%CI was 0.921-2.469, P = 0.103]. There was also no statistically significant difference in the surgical-related factors such as surgical site, surgical method, anesthesia, and surgical duration among the patients with different degrees of airflow limitation and different comprehensive assessment of symptoms. Among the 143 patients, 10 were admitted to ICU postoperation and 133 were not. Compared with the non-admitted ICU patients, patients admitted ICU were older (years old: 73.10±10.56 vs. 65.14±9.79, P < 0.05), had a higher modified Medical Research Council (mMRC) classification [1.5 (1.0, 2.0) vs. 1.0 (0, 2.0), P < 0.05], and had more frequent acute exacerbations per year [times: 1 (1, 2) vs. 1 (0, 1), P < 0.05]. There was also significant difference in surgical method between the two. Multivariate Logistic regression analysis showed that age and frequency of acute exacerbations per year were risk factors for postoperative admission to the ICU (age: OR = 1.093, 95%CI was 1.010-1.183, P = 0.028; frequency of acute exacerbations per year: OR = 2.400, 95%CI was 1.015-5.676, P = 0.046). Different levels of airflow restriction and symptom comprehensive assessment groupings in stable COPD patients are not associated with the risk of postoperative ICU admission. Age and frequency of acute exacerbations per year were risk factors for postoperative ICU admission.

The GETUG SEMITEP Trial: De-Escalating Chemotherapy in Good-Risk Metastatic Seminoma Based on Early FDG-PET/CT

Background: Negative positron emission tomography/computed tomography (FDG-PET/CT) predicts the absence of viable seminoma cells in residual disease after chemotherapy in men with metastatic seminoma. In this study, we assessed whether men with good-prognosis metastatic seminoma could be treated with 2 cycles of etoposide-cisplatin (EP) followed by only one cycle of carboplatin (CARBO) based on a negative interim FDG-PET/CT, thereby limiting the burden of treatment and toxicity. Methods: In this non-randomised, multicentre, phase 2 trial (NCT01887340), we enrolled patients with good-prognosis metastatic seminoma (stage IIB, IIC and III with a good prognosis according to the Medical Research Council classification). All patients with baseline-positive FDG-PET/CT received EP for two cycles. After completing the first two cycles, the patients underwent a second FDG-PET/CT scan to assess the response between days 17 and 20. Patients with persistent positive FDG-PET/CT (based on local review) proceeded directly to two additional EP cycles (for a total of 4 cycles); those who achieved FDG-PET/CT negativity received only one cycle of CARBO AUC=7. The primary outcome was the proportion of patients with a negative FDG-PET/CT on interim assessment who received de-escalating chemotherapy. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Findings: Between June 2013 and July 2017, 102 patients were enrolled in the study. Three patients were deemed ineligible or not evaluable; thus, 99 patients received treatment. After the first 2 EP cycles, FDG-PET/CT was available in 98 pts. Overall, 67 patients (68.4%; 95% CI: 58.2-77.4) had a negative FDG-PET/CT and proceeded to a single CARBO cycle. Twenty-seven patients (27.6%; 95% CI: 19.0-37.5) still had a positive FDG-PET/CT after 2 EP cycles; overall, 31 patients received two additional cycles of EP. After a median follow-up of 39.4 months, only 9 patients relapsed (3/31 in the EP group and 6/67 in the CARBO group). The 3-year PFS rate was 90.0% (95% CI: 74.4-96.5) in the EP group and 90.2% (95% CI: 80.2-95.5) in the CARBO group. One patient died from sepsis during the first two cycles. Interpretation: De-escalating treatment based on a negative FDG-PET/CT after 2 cycles of chemotherapy appears to be safe and feasible in most men with good-prognosis metastatic seminoma. Trial Registration: The trial was registered at ClinicalTrials.gov (NCT01887340). Funding Statement: Programme Hospitalier de Recherche Clinique (PHRC) from the Institut National du Cancer (INCA), France. Declaration of Interests: Yohann Loriot: Dr Loriot reports grants from CELSIUS, grants from SANOFI, grants and personal fees from JANSSEN, personal fees from ASTELLAS, grants and personal fees from MSD, personal fees from ASTRA ZENECA, personal fees from BMS, personal fees from SEATTLE GENETICS, personal fees from PFIZER, personal fees from ROCHE, personal fees from IMMUNOMEDICS outside the submitted work; Matthieu Texier: Dr Texier has nothing to disclose; Stephane Culine: Dr Culine has nothing to disclose; Aude Flechon: Dr Flechon has nothing to disclose; Antoine Thierry-Vuillemin: Dr Thierry-Vuillemin reports personal fees from Pfizer, Astra Zeneca, Sanofi, Janssen, Novartis, Ipsen, Roche, Bristol-Myers Squibb, MSD, Astellas; Gwenaelle Gravis: Dr Gravis has nothing to disclose; Lionel Geoffrois: Dr Geoffrois reports personal fees from BMS, personal fees from NOVARTIS, personal fees and other from IPSEN, personal fees from PFIZER, personal fees from A-Z, personal fees from MSD, outside the submitted work; Christine Chevreau: Dr Chevreau has nothing to disclose; Marine Gross-Goupil: Dr Gross-Goupil has nothing to disclose; Philippe Barthelemy: Dr Barthelemy reports advisory board and travels from BMS, advisory board from MSD, advisory board and travels from IPSEN, advisory board from EUSAPHARMA, advisory board from NOVARTIS, advisory board and travels from ROCHE, advisory board and travels from PFIZER, advisory board and travels from JANSSEN, advisory board from ASTELLAS, outside the submitted work; Emmanuelle Bompas: Dr Bompas has nothing to disclose; Hakim Mahammedi : Dr Mahammedi reports personal fees from Bayer, personal fees from BMS , personal fees from Roche , personal fees from MSD , personal fees from Astra Zeneca , personal fees from Sanofi , personal fees and other from Janssen , personal fees and other from Astellas , outside the submitted work; Brigitte Laguerre: Dr Laguerre has nothing to disclose; Sophie Abadie Lacourtoisie : Dr Abadie Lacourtoisie has nothing to disclose; Carole Helissey: Dr Helissey reports personal fees from Sanofi, Janssen, Astellas and Roche; Sylvain Ladoire : Dr Ladoire reports grants from Pfizer, grants from Astellas, grants from Roche , grants from Novartis , grants from BMS, grants from Ipsen, grants from Janssen, grants from Sanofi, outside the submitted work; Christine Abraham: Dr Abraham has nothing to disclose; Christophe Massard: Dr Massard reports Consultant/Advisory fees from Amgen, Astellas, Astra Zeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion; Serena Grimaldi: Dr Grimaldi has nothing to disclose; Karim Fizazi: Dr Fizazi reports Consultant/Advisory fees from Amgen, Astellas, Bayer, Jansen, Takeda, Sanofi, Orion, Essa, Genentech, Astra Zeneca, Clovis. Ethics Approval Statement: Written informed consent was obtained from all the patients. The study was approved by the ethics committee of Ile de France II (N°2013-02-12 MS1) and the French Healthcare Agency (N°130253B-12).

A Retrospective Case Series Reporting the Outcomes of Avance Nerve Allografts in the Treatment of Peripheral Nerve Injuries.

Acellular nerve allografts are a viable treatment modality for bridging nerve gaps. Several small studies have demonstrated results equal to those of autologous grafts; however, there is information lacking with regard to outcomes for wider indications. The authors evaluated the outcomes of patients treated with a nerve allograft in a variety of clinical situations. A retrospective chart analysis was completed between April of 2009 and October of 2017. Inclusion criteria were age 18 years or older at the time of surgery and treatment with a nerve allograft. Patients were excluded if they had not been followed up for a minimum of 6 months. The modified Medical Research Council Classification was used to monitor motor and sensory changes in the postoperative period. Two hundred seven nerve allografts were used in 156 patients; of these, 129 patients with 171 nerve allografts fulfilled the inclusion criteria. Seventy-seven percent of patients achieved a sensory outcome score of S3 or above and 36 percent achieved a motor score of M3 or above. All patients with chronic pain had improvement of their symptoms. Graft length and diameter were negatively correlated with reported outcomes. One patient elected to undergo revision surgery, and the original graft was shown histologically to have extensive central necrosis. Anatomically, allografts used for lower limb reconstruction yielded the poorest results. All chronic patients had a significantly lower postoperative requirement for analgesia, and allografts were effective in not only reducing pain but also restoring a functional level of sensation. This study supports the wider application of allografts in managing nerve problems. However, caution must be applied to the use of long grafts with larger diameters. Therapeutic, IV.

Outcome of Achilles tendon plication and transfer of peroneus longus to Achilles tendon for correction of dynamic calcaneo-valgus deformity of the foot in post-polio residual paralysis

Objective: Tendon transfers are indicated when dynamic muscle imbalance results in a deformity that interferes with ambulation or function of the extremities. Foot and ankle are the most dependent parts of the body and are subjected to greater strain than other parts. Calcaneo-valgus deformity is one of the common deformities seen in Post-Polio Residual Paralysis. A host of operative procedures have been described in the management of this deformity. We report the results of the study conducted in our institute where Achilles tendon plication and transfer of Peroneus Longus tendon to Achilles tendon has been done for dynamic calcaneo-valgus deformity of the foot in patients of post-polio residual paralysis. Methods: This is a prospective study of 37 patients with Calcaneovalgus deformity having Post-Polio Residual Paralysis presenting to Balaji Institute of Surgery, Research and Rehabilitation for the Disabled Hospital from December 2009 to December 2012. Informed consent was taken from the parents of all the patients. Ethical committee approval was also taken. Patients with age more than 7 years, ability to walk without support and Peroneal tendon having minimum motor power of grade 4 or 5 as per MRC classification are included in our study. Patients with fixed deformity at ankle joint or subtalar joint are excluded from the study. Pre-operative evaluation included detailed motor examination of the involved lower limbs as per MRC (Medical research council) classification, evaluation of deformity in the hip and knee and range of motion at ankle. AOFAS (American Orthopaedic Foot and Ankle Society) clinical rating system was used to assess the patient pre-operatively and post-operatively. The aggregate score of the AOFAS ankle-hind foot clinical rating scale pre and post operatively were analyzed with use of chi-square analysis. The level of significance of < 0.05 was considered to be significant. The surgical procedure was done under spinal anesthesia with the patient in lateral position under pneumatic tourniquet. A longitudinal incision is made starting from the tip of lateral malleolus midway between the posterior border of lateral malleolus & Achilles tendon to about 8-10cm proximally. Skin flaps are mobilized without dissecting the subcutaneous fat. The two peroneal tendons are identified as they pass down the leg and around the back of the lateral malleolus. The peroneus longus tendon is divided as distally as possible and mobilized. Similarly the Achilles tendon is identified. Plication of the Achilles tendon is done in its middle third with nylon sutures and the peroneus longus tendon is transferred through it using Fish-Mouth (Pulvertaft) tendon suturing technique and is secured over itself proximally under tension providing the tenodesis effect. While this is done the ankle is kept in plantar flexion. The deep fascia is closed over the tendon. Pneumatic tourniquet was released, and the incision was closed in layers after hemostasis was achieved. Below knee cast is applied with the foot in plantar flexion. Movements of the toes are encouraged after recovery from anesthesia. Active toe movements were encouraged in the cast. After six weeks sutures are removed and ankle foot orthoses are provided for another six weeks. During this period supervised active exercises for strengthening the Tendoachilles (static cycling exercise) are started. Patient is reassessed after six weeks and the orthoses is discarded at this stage. Conclusion: Our experience concludes that Achilles tendon plication and transfer of peroneus longus tendon to Achilles tendon is an excellent procedure which improves the dynamic calcaneo-valgus deformity of foot in patients with post-polio residual paralysis. The advantage of the procedure being easy to do with very low complication rate and improves the quality of life in patients with post-polio residual paralysis. 37 patients with the dynamic calcaneo-valgus deformity of foot in patients with post-polio residual paralysis were analyzed with average follow up period of 12.5 months. Dynamic calcaneo-valgus deformity of the foot was corrected in 89.18% of patients. The study fared with 89 percent patients satisfied with the results. The patients showed improvement in their activity limitation, maximum walking distance, gait and stability.

PS29MRC - a Novel Predictive Score for Response to Therapy in Acute Myeloid Leukemia

About 20-25% of patients with Acute Myeloid Leukemia (AML) have primary drug resistant disease and fail to achieve complete remission after induction therapy. These patients have an extremely poor prognosis and cannot reliably be identified prior to therapy with current methods. The aim of this work was to develop a predictive tool that can identify therapy resistant patients with high accuracy at the time of diagnosis.We used two independent Affymetrix gene expression (GE) data sets and standard molecular and clinical variables to develop a predictive score for response to cytarabine/anthracycline-based induction chemotherapy. The "training set 1" consisted of 407 adult AML patients enrolled in the AMLCG-1999 trial (GSE37642). Training set 2 included 449 adults treated in various HOVON trials (GSE6891). GE-based classifiers for primary treatment resistance were developed in training set 1 using a penalized logistic regression approach (Lasso). A cut off with a specificity of 90% was predefined in training set 1. Training set 2 was used to select the best classifier. The predictive score and cut off were then validated in a third, fully independent data set, comprising 260 patients enrolled in AMLCG-1999 and 2008 trials studied by RNA sequencing. Additionally, targeted amplicon sequencing data for 68 recurrently mutated genes in AML was available for training set 1 and the validation set.The final classifier (Predictive score 29 MRC - PS29MRC) consisted of 29 gene expression values and the cytogenetic risk group (defined according to the United Kingdom Medical Research Council (MRC) classification) and was calculated as a weighted sum of Lasso coefficients and predictor values.PS29MRC was a highly significant predictor of resistant disease in the validation set with an odds ratio of 2.32 (p=1.53x10-8, AUC: 0.75). We tested the signature in a multivariable model including all variables with univariate p-value <0.05. TP53 mutations, age and PS29MRC (OR: 1.70; p=0.0020) were left significant in the validation set. In comparison to published predictive classifiers like the model by Walter et al. (integrating information on age, performance status, white blood cell count, platelet count, bone marrow blasts, gender, type of AML, cytogenetics and NPM1 and FLT3-ITD status; OR: 1.27; p=0.00083; AUC: 0.70) or the modified molecular version of this score (OR: 1.37; p=0.0027; AUC: 0.63) PS29MRC reached superior predictive accuracy. (Walter et al.; Leukemia 2015)Since we aimed to develop a clinically useful score, we categorized PS29MRC to distinguish between patients who have a high probability of refractory disease and those who are likely to benefit from induction therapy (complete remission or complete remission with incomplete hematologic recovery). By applying the predefined cut off, we were able to reach a specificity of 90% and sensitivity of 46% in the validation set (OR: 7.83; p=6.06x10-9). The accuracy of PS29MRC was 77%. In the multivariable model the categorized classifier was highly significant (OR: 4.45; p=0.00040) and only age and TP53 mutations were left as significant variables again. Within the cytogenetic subgroups favorable (n=14; refractory: n=0; responders: n=13), intermediate (n=189; refractory: n=43; responders: n=136) and adverse (n=49; refractory: n=29; responders: n=15) the classifier showed an accuracy of 100%, 78% and 66%, respectively. Furthermore, the classifier predicted survival and was able to unravel the intermediate MRC subgroup (Figure).Additionally, genes included in our predictive signature seem to be involved in AML pathogenesis and potentially actively contribute to mechanisms responsible for primary therapeutic resistance. For example MIR-155HG, an already known parameter of inferior outcome in AML, contributed significantly to PS29MRC. There are currently ongoing trials with the novel inhibitor Pevonedistat that aim to modulate this target in AML.In summary we were able to develop a predictive risk classifier summarizing 29 gene expression values and the MRC classification that outperformed all currently used methods to predict refractory disease in intensively treated adult AML patients. PS29MRC demonstrates that it is possible to identify patients at risk of treatment failure in AML at diagnosis with high specificity. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A novel therapy to promote axonal fusion in human digital nerves.

Peripheral nerve injury can have a devastating impact on our military and veteran population. Current strategies for peripheral nerve repair include techniques such as nerve tubes, nerve grafts, tissue matrices, and nerve growth guides to enhance the number of regenerating axons. Even with such advanced techniques, it takes months to regain function. In animal models, polyethylene glycol (PEG) therapy has shown to improve both physiologic and behavioral outcomes after nerve transection by fusion of a portion of the proximal axons to the distal axon stumps. The objective of this study was to show the efficacy of PEG fusion in humans and to retrospectively compare PEG fusion to standard nerve repair. Patients with traumatic lacerations involving digital nerves were treated with PEG after standard microsurgical neurorrhaphy. Sensory assessment after injury was performed at 1 week, 2 weeks, 1 month, and 2 months using static two-point discrimination and Semmes-Weinstein monofilament testing. The Medical Research Council Classification (MRCC) for Sensory Recovery Scale was used to evaluate the level of injury. The PEG fusion group was compared to patient-matched controls whose data were retrospectively collected. Four PEG fusions were performed on four nerve transections in two patients. Polyethylene glycol therapy improves functional outcomes and speed of nerve recovery in clinical setting assessed by average MRCC score in week 1 (2.8 vs 1.0, p = 0.03). At 4 weeks, MRCC remained superior in the PEG fusion group (3.8 vs 1.3, p = 0.01). At 8 weeks, there was improvement in both groups with the PEG fusion cohort remaining statistically better (4.0 vs 1.7, p = 0.01). Polyethylene glycol fusion is a novel therapy for peripheral nerve repair with proven effectiveness in animal models. Clinical studies are still in early stages but have had encouraging results. Polyethylene glycol fusion is a potential revolutionary therapy in peripheral nerve repair but needs further investigation. Therapeutic study, level IV.

Can Processed Nerve Allografts be Used to Repair Nerve Injuries Greater than 4cm for the Return of Critical Function in the Upper Extremity?: Level 3 Evidence

Consulting Fee: AxoGen, Inc. (Safa)Speakers Bureau: AxoGen, Inc. (Safa, Buncke)Contracted Research: Lead site for Axogen-sponsored RANGER study (Buncke) Recent animal studies suggest acellular nerve allografts may provide inadequate regeneration compared to autografts for gaps greater than 40mm in rodents. To examine whether this observation translates to clinical practice, we queried a national nerve registry on processed nerve allograft (PNA) with autograft controls for injuries between 40-70mm. Based on clinical evidence and historical controls, we hypothesized that PNA would perform similar to nerve autograft in long gap upper extremity nerve injuries in humans. The RANGER registry is an IRB-approved, active database designed to collect injury, repair, safety and outcomes data for processed nerve allografts (Avance® Nerve Graft, AxoGen, Inc). Recently active control groups for autograft and conduit repair were added to RANGER. The registry database was queried for >40mm upper extremity nerve repairs with at least 9 months of quantitative follow-up data. Subject demographics and injury information were also evaluated for observable trends. Outcomes data were incorporated into the Medical Research Council Classification (MRCC) for sensory and motor function with meaningful recovery defined as S3/M3 or higher on the MRCC scale. Outcomes were compared to registry matched controls and historical data for nerve autograft. Twenty-seven subjects with 35 injuries were included. The groups consisted of PNA (n = 23) and nerve autograft (n = 12). Subject demographics, medical history, and concomitant injuries were comparable. PNA repairs were single stranded, caliber matched epineural repairs, while autografts were multi-strand cabled repairs. The PNA group contained a higher incidence of neuroma resections of digital nerves repaired in a delayed fashion. The average gap was 46±6mm and 48±8 mm for PNA and nerve autograft respectively. Meaningful recovery was comparable between the groups at 74% for the PNA and 67% for nerve autograft. In mixed nerve repairs reporting motor function, outcomes were also comparable with 5 of 6 and 6 of 7 repairs reporting return of motor function in the PNA and autograft groups respectively. There were no reported adverse events related to the treatment groups. See Table 1 for summary. •Clinically reported levels of meaningful recovery for >40mm processed nerve allografts are comparable to nerve autografts with both sensory and motor function outcomes.•No adverse events or revisions were reported.•Outcomes compare favorably to historical literature for nerve autograft.•The registry remains ongoing and continues to collect outcomes data on processed nerve allografts in long gap nerve reconstructions.

Outcomes of short-gap sensory nerve injuries reconstructed with processed nerve allografts from a multicenter registry study.

Short-gap digital nerve injuries are a common surgical problem, but the optimal treatment modality is unknown. A multicenter database was queried and analyzed to determine the outcomes of nerve gap reconstructions between 5 and 15 mm with processed nerve allograft. The current RANGER registry is designed to continuously monitor and compile injury, repair, safety, and outcomes data. Centers followed their own standard of care for treatment and follow-up. The database was queried for digital nerve injuries with a gap between 5 and 15 mm reporting sufficient follow-up data to complete outcomes analysis. Available quantitative outcome measures were reviewed and reported. Meaningful recovery was defined by the Medical Research Council Classification (MRCC) scale at S3-S4 for sensory function. Sufficient follow-up data were available for 24 subjects (37 repairs) in the prescribed gap range. Mean age was 43 years (range, 23-81). Mean gap was 11 ± 3 (5-15) mm. Time to repair was 13 ± 42 (0-215) days. There were 25 lacerations, 8 avulsion/amputations, 2 gunshots, 1 crush injury, and 1 injury of unknown mechanism. Meaningful recovery, defined as S3-S4 on the MRCC scales, was reported in 92% of repairs. Sensory recovery of S3+ or S4 was observed in 84% of repairs. Static 2PD was 7.1 ± 2.9 mm (n = 19). Return to light touch was observed in 23 out of 32 repairs reporting Semmes-Weinstein monofilament outcomes (SWMF). There were no reported nerve adverse events. Sensory outcomes for processed nerve allografts were equivalent to historical controls for nerve autograft and exceed those of conduit. Processed nerve allografts provide an effective solution for short-gap digital nerve reconstructions.

Evaluation of emergency nerve grafting for proper palmar digital nerve defects: A retrospective single centre study

HypothesisFinger trauma often results in discontinuity of the proper palmar digital nerves. The goal of this study was to retrospectively evaluate the clinical outcomes of emergency nerve grafting and the resulting donor site morbidity. Material and methodThree women and 13 men who had been operated between 2008 and 2012 were reviewed. The average patient age was 39 years (range 18–78). All were operated on an emergency basis. The average defect was 38mm long (range 15–60). The nerves were harvested from four sites: lateral antebrachial cutaneous nerve (12 cases), banked finger (2 cases), terminal portion of posterior interosseous nerve (1 case) and anterior interosseous nerve (1 case). The evaluation consisted of patient questioning and clinical examination of the treated finger and donor site. An objective sensory exam was also performed. The results were expressed according to the British Medical Research Council (MRC) classification. ResultsThere was little donor site morbidity (2 cases of symptomatic hypoesthesia, 1 case of scar hypersensitivity). Sixty-nine percent of patients stated that their grafted finger did not cause them any trouble during activities of daily living. Three patients required job retraining. Pain in the grafted finger was 0.6 (range 0–5) on the VAS. Normal sensation was restored in 31% of cases based on the monofilament sensory test; 25% had a slight decrease in touch sensitivity and 25% had reduced protective sensations. Weber's two-point discrimination test found 50% normal sensibility (threshold<6mm) and 6% with mediocre sensibility (threshold of 6–10mm). On the MRC grading scale, 50% of patients were at S4, 6% at S3+, 19% at S3, 12% at S2 and 12% at S1. ConclusionThere were 56% good results in this patient series (S3+/S4) and no patients at S0. Donor site morbidity was rare. Thus use of nerve grafting is still a relevant option in an emergency setting. Level of evidenceLevel IV.