Neuromuscular consequences of spinal cord injury: New mechanistic insights and clinical considerations.

The spinal cord facilitates communication between the brain and the body, containing intrinsic systems that work with lower motor neurons (LMNs) to manage movement. Spinal cord injuries (SCIs) can lead to partial paralysis and dysfunctions in muscles below the injury. While traditionally this paralysis has been attributed to disruptions in the corticospinal tract, a growing body of work demonstrates LMN damage is a factor. Motor units, comprising the LMN and the muscle fibers with which they connect, are essential for voluntary movement. Our understanding of their changes post-SCI is still emerging, but the health of motor units is vital, especially when considering innovative SCI treatments like nerve transfer surgery. This review seeks to collate current literature on how SCI impact motor units and explore neuromuscular clinical implications and treatment avenues. SCI reduced motor unit number estimates, and surviving motor units had impaired signal transmission at the neuromuscular junction, force-generating capacity, and excitability, which have the potential to recover chronically, yet the underlaying mechanisms are unclear. Furthermore, electrodiagnostic evaluations can aid in assessing the health lower and upper motor neurons, identify suitable targets for nerve transfer surgeries, and detect patients with time sensitive injuries. Lastly, many electrodiagnostic abnormalities occur in both chronic and acute SCI, yet factors contributing to these abnormalities are unknown. Future studies are required to determine how motor units adapt following SCI and the clinical implications of these adaptations.

Evaluating peripheral neuromuscular function with brief movement-evoked pain.

Movement-evoked pain is an understudied manifestation of musculoskeletal conditions that contributes to disability, yet little is known about how the neuromuscular system responds to movement-evoked pain. The present study examined whether movement-evoked pain impacts force production, electromyographic (EMG) muscle activity, and the rate of force development (RFD) during submaximal muscle contractions. Fifteen healthy adults (9 males; age = 30.3 ± 10.2 yr, range = 22-59 yr) performed submaximal isometric first finger abduction contractions without pain (baseline) and with movement-evoked pain induced by laser stimulation to the dorsum of the hand. Normalized force (% maximal voluntary contraction) and RFD decreased by 11% (P < 0.001) and 15% (P = 0.003), respectively, with movement-evoked pain, without any change in normalized peak EMG (P = 0.77). Early contractile RFD, force impulse, and corresponding EMG amplitude computed within time segments of 50, 100, 150, and 200 ms relative to the onset of movement were also unaffected by movement-evoked pain (P > 0.05). Our results demonstrate that movement-evoked pain impairs peak characteristics and not early measures of submaximal force production and RFD, without affecting EMG activity (peak and early). Possible explanations for the stability in EMG with reduced force include antagonist coactivation and a reorganization of motoneuronal activation strategy, which is discussed here.NEW & NOTEWORTHY We provide neurophysiological evidence to indicate that peak force and rate of force development are reduced by movement-evoked pain despite a lack of change in EMG and early rapid force development in the first dorsal interosseous muscle. Additional evidence suggests that these findings may coexist with a reorganization in motoneuronal activation strategy.

Segmental infralesional pathological spontaneous activity in subacute traumatic spinal cord injury.

INTRODUCTION/AIMS: There is a dearth of knowledge regarding the status of infralesional lower motor neurons (LMNs) in individuals with traumatic cervical spinal cord injury (SCI), yet there is a growing need to understand how the spinal lesion impacts LMNs caudal to the lesion epicenter, especially in the context of nerve transfer surgery to restore several key upper limb functions. Our objective was to determine the frequency of pathological spontaneous activity (PSA) at, and below, the level of spinal injury, to gain an understanding of LMN health below the spinal lesion. METHODS: Ninety-one limbs in 57 individuals (53 males, mean age = 44.4 ± 16.9 years, mean duration from injury = 3.4 ± 1.4 months, 32 with motor complete injuries), were analyzed. Analysis was stratified by injury level as (1) C4 and above, (2) C5, and (3) C6-7. Needle electromyography was performed on representative muscles innervated by the C5-6, C6-7, C7-8, and C8-T1 nerve roots. PSA was dichotomized as present or absent. Data were pooled for the most caudal infralesional segment (C8-T1). RESULTS: A high frequency of PSA was seen in all infralesional segments. The pooled frequency of PSA for all injury levels at C8-T1 was 68.7% of the limbs tested. There was also evidence of PSA at the rostral border of the neurological level of injury, with 58.3% of C5-6 muscles in those with C5-level injuries. DISCUSSION: These data support a high prevalence of infralesional LMN abnormalities following SCI, which has implications to nerve transfer candidacy, timing of the intervention, and donor nerve options.

Nerve Transfer After Cervical Spinal Cord Injury: Who Has a "Time Sensitive" Injury Based on Electrodiagnostic Findings?

OBJECTIVE: To use the ulnar compound muscle action potential (CMAP) to abductor digiti minimi (ADM) to identify the proportion of individuals with cervical spinal cord injury (SCI) who have lower motor neuron (LMN) abnormalities involving the C8-T1 spinal nerve roots, within 3-6 months, and thus may influence the response to nerve transfer surgery. DESIGN: Retrospective analysis of prospectively collected data. Data were analyzed from European Multicenter Study About SCI database. SETTING: Multi-center, academic hospitals. PARTICIPANTS: We included 79 subjects (age=41.4±17.7, range:16-75; 59 men; N=79), who were classified as cervical level injuries 2 weeks after injury and who had manual muscle strength examinations that would warrant consideration for nerve transfer (C5≥4, C8<3). INTERVENTIONS: None. MAIN OUTCOME MEASURES: The ulnar nerve CMAP amplitude to ADM was used as a proxy measure for C8-T1 spinal segment health. CMAP amplitude was stratified into very abnormal (<1.0 mV), sub-normal (1.0-5.9 mV), and normal (>6.0 mV). Analysis took place at 3 (n=148 limbs) and 6 months (n=145 limbs). RESULTS: At 3- and 6-month post-injury, 33.1% and 28.3% of limbs had very abnormal CMAP amplitudes, respectively, while in 54.1% and 51.7%, CMAPs were sub-normal. Median change in amplitude from 3 to 6 months was 0.0 mV for very abnormal and 1.0 mV for subnormal groups. A 3-month ulnar CMAP <1 mV had a positive predictive value of 0.73 (95% CI 0.69-0.76) and 0.78 (95% CI 0.75-0.80) for C8 and T1 muscle strength of 0 vs 1 or 2. CONCLUSION: A high proportion of individuals have ulnar CMAPs below the lower limit of normal 3- and 6-month post cervical SCI and may also have intercurrent LMN injury. Failure to identify individuals with LMN denervation could result in a lost opportunity to improve hand function through timely nerve transfer surgeries.

Motor and autonomic concomitant health improvements with neuromodulation and exercise (MACHINE) training: a randomised controlled trial in individuals with spinal cord injury.

INTRODUCTION: Motor and autonomic dysfunctions are widespread among people with spinal cord injury (SCI), leading to poor health and reduced quality of life. Exercise interventions, such as locomotor training (LT), can promote sensorimotor and autonomic recovery post SCI. Recently, breakthroughs in SCI research have reported beneficial effects of electrical spinal cord stimulation (SCS) on motor and autonomic functions. Despite literature supporting the independent benefits of transcutaneous SCS (TSCS) and LT, the effect of pairing TSCS with LT is unknown. These therapies are non-invasive, customisable and have the potential to simultaneously benefit both sensorimotor and autonomic functions. The aim of this study is to assess the effects of LT paired with TSCS in people with chronic SCI on outcomes of sensorimotor and autonomic function. METHODS AND ANALYSIS: Twelve eligible participants with chronic (>1 year) motor-complete SCI, at or above the sixth thoracic segment, will be enrolled in this single-blinded, randomised sham-controlled trial. Participants will undergo mapping for optimisation of stimulation parameters and baseline assessments of motor and autonomic functions. Participants will then be randomly assigned to either LT+TSCS or LT+Sham stimulation for 12 weeks, after which postintervention assessments will be performed to determine the effect of TSCS on motor and autonomic functions. The primary outcome of interest is attempted voluntary muscle activation using surface electromyography. The secondary outcomes relate to sensorimotor function, cardiovascular function, pelvic organ function and health-related quality of life. Statistical analysis will be performed using two-way repeated measures Analysis of variance (ANOVAs) or Kruskal-Wallis and Cohen's effect sizes. ETHICS AND DISSEMINATION: This study has been approved after full ethical review by the University of British Columbia's Research Ethics Board. The stimulator used in this trial has received Investigation Testing Authorisation from Health Canada. Trial results will be disseminated through peer-reviewed publications, conference presentations and seminars. TRIAL REGISTRATION NUMBER: NCT04726059.

Patient perspectives and self-rated knowledge of nerve transfer surgery for restoring upper limb function in spinal cord injury.

BACKGROUND: Nerve transfer surgery has the potential to restore upper limb function in patients with spinal cord injury (SCI); however, there has been limited exploration of patient perception of nerve transfer. OBJECTIVE: To explore the perspectives of patients with chronic SCI (>2 years from injury) on nerve transfer surgery, and to determine if an educational intervention improved participants' perceived knowledge levels about the procedure. DESIGN: Mixed-methods study including qualitative semi-structured interviews and self-reported rating scales. Pre- and post-interviews were completed following an educational presentation. SETTING: Two local SCI clinics. PARTICIPANTS: Ten patients with chronic traumatic SCI and neurological level of injury C3-C7 (motor complete or incomplete), recruited via snowball sampling (six male, four female). INTERVENTION: An educational slide presentation on nerve transfer concepts. MAIN OUTCOME MEASURES: The primary study outcome measure is the participants' responses to interview questions. The secondary study outcome measure is their self-reported knowledge levels of nerve transfer before and after education. RESULTS: Regaining upper limb function was a priority for all participants. Although most participants had heard of nerve transfer, none were offered it at the time of their SCI, and only two stated that they had any peers who had undergone the procedure. The educational module significantly increased self-rated scores on understanding of nerve transfer (p < .05). Although all participants were open to nerve transfer after the educational module, they described weighing different factors, including (1) potential for loss versus gain of function, (2) inadequate knowledge about nerve transfer, (3) recovery time, and (4) determining their eligibility for the surgery. CONCLUSIONS: These findings suggest that people with SCI have limited understanding of nerve transfer as a potential option and would benefit from educational opportunities to help them make informed decisions. This study may inform the development of patient resources to improve pre-surgical consultation and informed decision-making.

Effects of non-invasive spinal cord stimulation on lower urinary tract, bowel, and sexual functions in individuals with chronic motor-complete spinal cord injury: Protocol for a pilot clinical trial.

INTRODUCTION: Electrical spinal cord neuromodulation has emerged as a leading intervention for restoring autonomic functions, such as blood pressure, lower urinary tract (LUT), bowel, and sexual functions, following spinal cord injury (SCI). While a few preliminary studies have shown the potential effect of non-invasive transcutaneous spinal cord stimulation (tSCS) on autonomic recovery following SCI, the optimal stimulation parameters, as well as real-time and long-term functional benefits of tSCS are understudied. This trial entitled "Non-invasive Neuromodulation to Treat Bladder, Bowel, and Sexual Dysfunction following Spinal Cord Injury" is a pilot trial to examine the feasibility, dosage effect and safety of tSCS on pelvic organ function for future large-scale randomized controlled trials. METHODS AND ANALYSIS: Forty eligible participants with chronic cervical or upper thoracic motor-complete SCI will undergo stimulation mapping and assessment batteries to determine the real-time effect of tSCS on autonomic functions. Thereafter, participants will be randomly assigned to either moderate or intensive tSCS groups to test the dosage effect of long-term stimulation on autonomic parameters. Participants in each group will receive 60 minutes of tSCS per session either twice (moderate) or five (intensive) times per week, over a period of six weeks. Outcome measures include: (a) changes in bladder capacity through urodynamic studies during real-time and after long-term tSCS, and (b) resting anorectal pressure determined via anorectal manometry during real-time tSCS. We also measure assessments of sexual function, neurological impairments, and health-related quality of life using validated questionnaires and semi-structured interviews. ETHICS AND DISSEMINATION: Ethical approval has been obtained (CREB H20-01163). All primary and secondary outcome data will be submitted to peer-reviewed journals and disseminated among the broader scientific community and stakeholders.

Reverse End-to-Side Nerve Transfer for Severe Ulnar Nerve Injury: A Western Canadian Multicentre Prospective Nonrandomized Cohort Study.

BACKGROUND: Reverse end-to-side (RETS) nerve transfer has become increasingly popular in patients with severe high ulnar nerve injury, but the reported outcomes have been inconsistent. OBJECTIVE: To evaluate the "babysitting effect," we compared outcomes after anterior interosseous nerve RETS transfer with nerve decompression alone. To evaluate the source of regenerating axons, a group with end-to-end (ETE) transfer was used for comparisons. METHODS: Electrophysiology measures were used to quantify the regeneration of anterior interosseous nerve (AIN) and ulnar nerve fibers while functional recovery was evaluated using key pinch and Semmes-Weinstein monofilaments. The subjects were followed postsurgically for 3 years. RESULTS: Sixty-two subjects (RETS = 25, ETE = 16, and decompression = 21) from 4 centers in Western Canada were enrolled. All subjects with severe ulnar nerve injury had nerve compression at the elbow except 10 in the ETE group had nerve laceration or traction injury. Postsurgically, no reinnervation from the AIN to the abductor digiti minimi muscles was seen in any of the RETS subjects. Although there was no significant improvement in compound muscle action potentials amplitudes and pressure detection thresholds in the decompression and RETS group, key pinch strength significantly improved in the RETS group ( P < .05). CONCLUSION: The results from published clinical trials are conflicting in part because crossover regeneration from the donor nerve has never been measured. Unlike those with ETE nerve transfers, we found that there was no crossover regeneration in the RETS group. The extent of reinnervation was also no different from decompression surgery alone. Based on these findings, the justifications for this surgical technique need to be carefully re-evaluated.

Effect of the COVID-19 pandemic on individuals with spinal cord injury: Mental health and use of telehealth.

INTRODUCTION: Limited access to health care services and the self-isolation measures due to the coronavirus disease 2019 (COVID-19) pandemic may have had additional unintended negative effects, affecting the health of individuals with spinal cord injury (SCI). OBJECTIVES: To examine the perceived influence of the COVID-19 pandemic on individuals with SCI. First, this study looked to understand how the pandemic affected the use and perception of telehealth services for these individuals. Second, it investigated the effect of COVID-19 on mental health. DESIGN: Cross-sectional online survey. SETTING: Individuals with SCI living in the community in British Columbia, Canada. PATIENTS: This survey was offered to individuals with SCI and had 71 respondents, with 34% living in a rural setting and 66% in an urban setting. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Telehealth utility, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7 (GAD-7), Fear of COVID-19 scale (FCV-19S), and Perceived Vulnerability to Disease (PVD). RESULTS: Telehealth use in the SCI population has increased from 9.9% to 25.4% over the pandemic, with rates of telehealth use in urban centers nearing those of rural participants. Thirty-one percent of respondents had probable depression and 7.0% had probable generalized anxiety disorder as measured by a score of ≥10 on the PHQ-9 and GAD-7, respectively. The mean scores on FCV-19S and PVD were 17.0 (6.6 SD) and 4.29 (1.02 SD), respectively. CONCLUSION: Telehealth use during COVID-19 has more than doubled. It is generally well regarded by respondents, although only a fourth of the SCI population has reported its use. With this in mind, it is important to understand the barriers to further adoption. In addition, higher rates of probable depression were seen than those estimated by pre-pandemic studies in other countries.

Clinical electrodiagnostic evaluation for nerve transfer surgery in spinal cord injury: a new indication and clinical pearls.

In this review, we highlight the important role of the clinical electrodiagnostic (EDX) evaluation after cervical spinal cord injury (SCI). Our discussion focuses on the need for timely, frequent, and accurate EDX evaluations in the context of nerve transfer surgery to restore critical upper limb functions, including elbow extension, hand opening, and hand closing. The EDX evaluation is crucial to define the extent of lower motor neuron lesions and determine candidacy for surgery. We also discuss the important role of the postoperative EDX evaluation in determining prognosis and supporting rehabilitation. We propose a practical framework for EDX evaluation in this clinical setting.

Evaluation of muscle strength following peripheral nerve surgery: A scoping review.

Peripheral nerve injury (PNI) can result in devastating loss of function, often with poor long-term prognosis. Increased use of peripheral nerve surgical techniques (eg, nerve transfer, nerve grafting, and nerve repair) has resulted in improved muscle strength and other functional outcomes in patients with PNI. Muscle strength has largely been evaluated with the British Medical Research Council (MRC) scale. MRC is convenient to use in clinical settings, but more robust measures of muscle function are necessary to fully elucidate patient recovery. This scoping review aims to examine alternative instruments used to assess muscle function in studies of peripheral nerve surgery for PNI of the upper and lower limbs. A scoping review was conducted using Ovid MEDLINE, CINAHL, EMBASE, and PubMed databases in May and December of 2020, yielding a total of 20 studies pertaining to the review question. Studies pertaining to handheld dynamometry, grip and pinch dynamometry, Rotterdam Intrinsic Hand Myometers, isokinetic dynamometry, ultrasonography, and electromyography were reviewed. We provide a synopsis of each method and current clinical applications and discuss potential benefits, disadvantages, and areas of future research.

Lower Motor Neuron Abnormality in Chronic Cervical Spinal Cord Injury: Implications for Nerve Transfer Surgery.

Nerve transfer surgery (NT) constitutes an exciting option to improve upper limb functions in chronic spinal cord injury (SCI), but requires intact sublesional lower motor neuron (LMN) health. The purpose of this study was to characterize patterns of LMN abnormality in nerve-muscle groups that are the potential recipients of NT, using a standardized electrodiagnostic examination, in individuals with chronic SCI (injury duration >2 years, injury levels C4-T1). The LMN abnormality was determined using a semihierarchical approach, combining the amplitude compound muscle action potential (CMAP) and abnormal spontaneous activity on needle electromyography (EMG). Ten participants (46 potential recipient muscles) were included (median age, 42.5 years; six males and four females; median duration from injury, 15.5 years). A high frequency of LMN abnormality was observed (87%), although there was substantial variation within and between individuals. No statistically significant discordance was observed between LMN abnormality on CMAP and EMG (p = 0.24), however, 50% of muscles with normal CMAP demonstrated abnormal spontaneous activity. The high frequency of LMN abnormality in recipient nerve-muscle groups has implications to candidate selection for NT surgery in chronic SCI and supports the important role of the pre-operative electrodiagnostic examination. Our results further support the inclusion of both CMAP and needle EMG parameters for characterization of LMN health. Although the number of nerve-muscle groups with normal LMN health was small (13%), this underscores the neurophysiological potential of some patients with chronic injuries to benefit from NT surgery.

Test-retest reliability of the Valsalva maneuver in spinal cord injury.

Objective: To determine the test-retest reliability of quantitative and qualitative baroreflex sensitivity (BRS) parameters derived from the Valsalva maneuver (VM) in individuals with traumatic cervical SCI.Design: Test-retest reliability.Setting: Tertiary rehabilitation center.Participants: Fourteen participants with cervical SCI (ranging from C3-C8 neurological level).Outcome Measurements: Beat-to-beat systolic blood pressure (SBP) traces (finger photoplethysmography) were obtained during a 15-second forced expiration at two time points (7.6 ± 2.9 days between sessions) to assess VM reliability. Test-retest reliability of BRS metrics from derived from the VM (Valsalva ratio; VR, pressure recovery time; PRT, vagal baroreflex sensitivity; BRSv, adrenergic baroreflex sensitivity; BRSa1, and total recovery; TR) were assessed by intra-class correlation coefficient (ICC, with 95% confidence interval; CI) and by qualitative reproducibility (V, N, or M pattern).Results: ICCs for quantitative parameters were (CI): VR = 0.894 (0.703-0.965), TR = 0.927 (0.789-0.976), BRSa1 = 0.561 (0.149-0.911), PRT = 0.728 (0.343-0.904), BRSv = 0.243 (-0.309-0.673). Qualitatively, 12 subjects (85.7%) demonstrated reproducible VM patterns at both time points (3 "M" pattern, 8 "V" pattern and one "N" pattern).Conclusion: VR (a measure of cardiovagal function) and TR (a measure of sympathetic adrenergic function) are reliable quantitative parameters that can be derived from SBP response to VM in participants with SCI. Qualitative waveform analysis was reproducible in 12/14 participants. This provides the foundational evidence required to pursue further validity testing to establish a role for VM in the assessment of autonomic functions in SCI.

Can Magnetic Resonance Imaging Reveal Lower Motor Neuron Damage after Traumatic Spinal Cord Injury? A Scoping Review.

Restoring muscle function to patients with spinal cord injuries (SCIs) will invariably require a functioning lower motor neuron (LMN). As techniques such as nerve transfer surgery emerge, characterizing the extent of LMN damage associated with SCIs becomes clinically important. Current methods of LMN diagnosis have inherent limitations that could potentially be overcome by the development of magnetic resonance imaging (MRI) biomarkers: specific features on MRI that are indicative of LMN integrity. To identify research on MRI biomarkers of LMN damage in the acute phase after SCI, we searched PubMed, EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials for articles published from inception to April 27, 2021. Overall, 2 of 58 unique articles screened met our inclusion criteria, both of which were small studies. We therefore identify MRI biomarkers of LMN damage overlying SCI as a notable gap in the literature. Because of the lack of existing literature on this specific problem, we further our discussion by examining concepts explored in research characterizing MRI biomarkers of spinal cord and neuronal damage in different contexts that may provide value in future work to identify a biomarker for LMN damage in SCI. We conclude that MRI biomarkers of LMN damage in SCI is an underexplored, but promising, area of research as emerging, function-restoring therapies requiring this information continue to advance.

Relationship Between Sensibility Tests and Functional Outcomes in Patients With Traumatic Upper Limb Nerve Injuries: A Systematic Review.

OBJECTIVE: To investigate which tests of hand sensibility correlate with functional outcomes in patients with upper limb traumatic nerve injuries and to assess if composite scales of sensibility correlate with functions. DATA SOURCES: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched in May 2020, with a supplementary search in July 2020. Reference lists of the included publications were hand searched. STUDY SELECTION: Database search found 2437 records. Eligible studies reported on inferential association between sensibility tests and functions pertaining to adults after upper limb nerve repair. Two reviewers independently assessed eligibility. Fifteen publications were included. DATA EXTRACTION: Extracted data contain patient characteristics, surgical procedure, follow-up duration, sensibility tests, and functional assessments. Two reviewers independently assessed data quality. DATA SYNTHESIS: Fifteen publications involving 849 patients were reviewed. All publications reported on median and/or ulnar nerve injuries. Monofilament tests correlated with Short-Form Health Survey (r=0.548, P<.05), pick-up test (r=0.45, P<.05), and function domain of Patient-Rated Wrist and Hand Evaluation Questionnaire (PRWHE) (r=0.58, P<.05). The 8 studies of static and moving 2-point discrimination provided conflicting correlations with activities of daily living (ADL) and/or the pick-up test. Data for area localization and object/shape identification were equivocal as well. No data were found for Ten test and vibration tests. Rosén score sensory domain correlated with ADL (r=0.59; 95% confidence interval [CI], 0.41-0.72) and PRWHE function domain (r=-0.56, P<.05). Medical Research Council sensory scale was related to pick-up test; return to work status; and Disabilities of the Arm, Shoulder, and Hand questionnaire. CONCLUSIONS: Monofilament tests allow practitioners to gather sensibility data meaningful to patients' overall recovery of functions after upper limb nerve trauma. For 2-point discrimination and other sensibility tests, practitioners should be aware that improvement in test performance does not necessarily translate to improved hand function. Findings from the composite scales indicate that hand sensibility, in general, is related to functions. Future research on other common sensibility tests is recommended to explore how the test relates to patients' functions.

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer.

OBJECTIVE: To review the pharmacology, efficacy, and safety of sacituzumab govitecan (-hziy; IMMU-132, Trodelvy) for patients with metastatic triple-negative breast cancer (mTNBC) who have received at least 2 prior therapies for metastatic disease. DATA SOURCES: A literature search was conducted utilizing PubMed and MEDLINE databases, applicable published abstracts, and ongoing studies from ClinicalTrials.gov between January 1, 1981, and September 3, 2020. Keywords included sacituzumab govitecan (-hziy), IMMU-132, Trop-2 (trophoblast cell-surface antigen 2), and TACSTD2. STUDY SELECTION AND DATA EXTRACTION: All English-language trials involving sacituzumab govitecan for mTNBC were included and discussed. DATA SYNTHESIS: Sacituzumab govitecan is an antibody-drug conjugate targeted for Trop-2 and conjugated to the topoisomerase-1 inhibitor SN-38. It was granted accelerated Food and Drug Administration approval based on a phase I/II single-arm, multicenter study (n = 108), which reported an overall response rate of 33.3% and median duration of response of 7.7 months (95% CI = 4.9-10.8 months). Common adverse reactions include nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, abdominal pain, and respiratory infection. A confirmatory, randomized phase III clinical trial is ongoing (NCT02574455). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review covers the efficacy, safety, and clinical use of sacituzumab govitecan, a third-line drug with activity in mTNBC. CONCLUSION: Sacituzumab govitecan is a novel targeted treatment with promising activity in mTNBC.

Access to Allied Health Care Services in Canadian Interdisciplinary Complex Nerve Injury Programs.

Nerve transfer surgery for patients with nerve and spinal cord injuries can result in dramatic functional improvements. As a result, interdisciplinary complex nerve injury programs (CNIPs) have been established in many Canadian centers, providing electrodiagnostic and surgical consultations in a single encounter. We sought to determine which allied health care services are included in Canadian CNIPs, at the 3rd Annual Canadian Peripheral Nerve Symposium. Twenty CNIPs responded to a brief survey and reported access as follows: occupational therapy = 60%, physiotherapy = 40%, social work = 20%, and mental health = 10%. Access to allied health services is variable in CNIPs across Canada, possibly resulting in heterogeneity in patient care.

Progression-Free Survival for Real-World Use of Palbociclib in Hormone Receptor-Positive Metastatic Breast Cancer.

BACKGROUND: Additional use of cyclin-dependent kinase 4/6 inhibitors with endocrine therapy improves progression-free survival (PFS) in advanced hormone receptor (HR)-positive HER2-negative breast cancer. However, neutropenia is a common reason for dose reductions, leading to concerns about palbociclib efficacy at lower doses. A safety analysis confirmed no PFS differences between palbociclib doses in the second-line setting, but to our knowledge, this has not been evaluated for first-line treatment. PATIENTS AND METHODS: In this retrospective, single-center cohort study we evaluated real-world use of first-line palbociclib with aromatase inhibitor (AI) treatment in HR-positive, HER2-negative metastatic breast cancer patients who received treatment between February 2015 and July 2017. The primary objective was to determine PFS of treatment with palbociclib and an AI in a real-world first-line setting. Secondary objectives included determining the PFS for patients treated with palbociclib on the basis of final doses, time to first dose reduction, time to treatment failure (TTF), and safety. RESULTS: Seventy patients were included in the final analysis. Median PFS was 26.4 months. No significant differences in PFS were observed on the basis of final doses of palbociclib (P = .77). Time to first dose reduction was 2.3 months. Median TTF was 26.1 months. Dose delays, reductions, and Grade 3/4 neutropenia were common (63%, n = 44; 57%, n = 40; and 62%, n = 43, respectively). CONCLUSION: Real-world first-line palbociclib treatment produced outcomes similar to those in PALOMA-2 (Palbociclib and Letrozole in Advanced Breast Cancer) (median PFS 26.4 months vs. 24.8 months) despite more dose reductions (57%, n = 40 vs. 36%, n = 160) and shorter time to first dose reduction (2.3 vs. 3.0 months). No significant differences in PFS were observed for the varying palbociclib doses. Palbociclib dose reductions might not significantly affect PFS in the first-line setting.

Time to treatment failure of palbociclib and letrozole as second-line therapy or beyond in hormone receptor-positive advanced breast cancer.

PURPOSE: The management of endocrine therapy resistance is one of the most challenging facets of advanced breast cancer treatment. Palbociclib is an inhibitor of cyclin-dependent kinases 4 and 6 approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer in combination with fulvestrant in postmenopausal women with disease progression following endocrine therapy. However, treatment responsiveness of tumors to palbociclib after multiple lines of endocrine therapy is not clearly established. The purpose of this study was to determine the efficacy of palbociclib and letrozole in patients pretreated with one or more lines of endocrine therapy. METHODS: This was a single-center, retrospective cohort study of all postmenopausal hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer patients who received palbociclib and letrozole as a second-line endocrine therapy or beyond (and no prior cyclin-dependent kinases 4 and 6 inhibitor therapy) between February 1, 2015, and July 31, 2016. The primary objective was to evaluate time to treatment failure of palbociclib in combination with letrozole as a second-line of therapy or beyond. RESULTS: Fifty-three patients meeting eligibility criteria were included in the analysis. For the primary outcome, the median time to treatment failure of palbociclib and letrozole was 6.3 months (95% CI 3.1-7.4 months). Progression-free survival of palbociclib and letrozole therapy was 6.4 months (95% CI 4.9-8.3 months). CONCLUSIONS: Palbociclib and letrozole therapy is a viable, effective treatment option for metastatic breast cancer patients who were not exposed to cyclin-dependent kinases 4 and 6 inhibitors as a first-line endocrine therapy. The benefits of palbociclib and letrozole therapy were seen without excessive toxicity, and although neutropenia was common, it may be managed with dose reduction.