Targeted Muscle Reinnervation at the Time of Amputation Decreases Recurrent Symptomatic Neuroma Formation.

BACKGROUND: Targeted muscle reinnervation (TMR) is an effective technique for the prevention and management of phantom limb pain (PLP) and residual limb pain (RLP) among amputees. The purpose of this study was to evaluate symptomatic neuroma recurrence and neuropathic pain outcomes between cohorts undergoing TMR at the time of amputation (ie, acute) versus TMR following symptomatic neuroma formation (ie, delayed). METHODS: A cross-sectional, retrospective chart review was conducted using patients undergoing TMR between 2015 and 2020. Symptomatic neuroma recurrence and surgical complications were collected. A subanalysis was conducted for patients who completed Patient-Reported Outcome Measurement Information System (PROMIS) pain intensity, interference, and behavior scales and an 11-point numeric rating scale (NRS) form. RESULTS: A total of 105 limbs from 103 patients were identified, with 73 acute TMR limbs and 32 delayed TMR limbs. Nineteen percent of the delayed TMR group had symptomatic neuromas recur in the distribution of original TMR compared with 1% of the acute TMR group ( P < 0.05). Pain surveys were completed at final follow-up by 85% of patients in the acute TMR group and 69% of patients in the delayed TMR group. Of this subanalysis, acute TMR patients reported significantly lower PLP PROMIS pain interference ( P < 0.05), RLP PROMIS pain intensity ( P < 0.05), and RLP PROMIS pain interference ( P < 0.05) scores in comparison to the delayed group. CONCLUSIONS: Patients who underwent acute TMR reported improved pain scores and a decreased rate of neuroma formation compared with TMR performed in a delayed fashion. These results highlight the promising role of TMR in the prevention of neuropathic pain and neuroma formation at the time of amputation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Physical clinical care and artificial-intelligence-guided core resistance training improve endurance and patient-reported outcomes in subjects with lower back pain.

BACKGROUND: Low back pain is an extremely prevalent issue with an extensive impact, ranging from decreased quality of life to lost years of productivity. Many interventions have been developed to alleviate chronic lower back pain, yet it remains a widespread problem. The objective of this study was to examine the role of artificial intelligence guided resistance training relative to clinical variables in subjects experiencing lower back pain. METHODS: 69 out of 108 enrolled and 92 accrued subjects completed the 8-week intervention. Subjects were randomized into four groups (Control, Training, Clinical, or Combined). The Training cohort received supervised artificial-intelligence-guided core-focused resistance training while the Clinical group received clinical care. The Combined group received both clinical care and artificial-intelligence-guided training and the Control group received no treatment. Participants were evaluated using functional testing and patient-reported outcomes at baseline, 4 weeks, and 8 weeks. FINDINGS: In the clinical tests, the Clinical and Combined cohorts showed increased total time for isometric extensor endurance and the Clinical cohort increased total distance traveled in the 6-min walk test at 8 weeks. The Training, Clinical, and Combined groups showed improvements in Patient-reported outcomes after 8 weeks. Most of the significant improvements were only seen at the 8-week evaluation for both the clinical evaluations and Patient-reported outcomes. The Control group did not show significant improvements in any outcome measures. INTERPRETATION: The present data indicate that core-focused interventions, including artificial-intelligence-guided moderate-resistance exercise, can increase objective functional outcomes and patient satisfaction using Patient-reported outcomes in individuals with lower back pain.

High pre-treatment neutrophil-to-lymphocyte ratio as a prognostic marker for worse survival in patients with recurrent/metastatic cervical cancer treated with immune checkpoint inhibitors.

Objective: To evaluate the association between pre-treatment neutrophil-to-lymphocyte ratio (NLR) and survival outcomes among patients with recurrent/metastatic cervical cancer treated with PD-1/PD-L1 inhibitors. Methods: A retrospective analysis of patients with recurrent/metastatic cervical cancer treated with PD-1/PD-L1 inhibitors from 2016 to 2021 was conducted. Progression free survival (PFS) and overall survival (OS) outcomes were assessed for patients stratified by NLR (<8 vs ≥ 8) utilizing Kaplan-Meier method. Univariable analysis was performed to compare baseline characteristics between the two groups. Results: A total of 49 patients were included in analysis. A majority of patients had squamous cell histology (57%), were PD-L1 positive (55%), received ≤ 1 prior lines of systemic therapy (57%), and had distant metastatic disease at the time of treatment (69%). The groups were well-balanced with respect to age, race, histology, smoking status, PD-L1 positivity, prior lines of treatment (≤1 vs > 1), prior radiation therapy, ECOG performance status, and disease distribution for patients with a NLR < 8 (n = 35) compared to those with a NLR ≥ 8 (n = 14). A pre-treatment NLR of < 8 was associated with improved survival (p < 0.01), with 57% (95% CI: 41%, 78%) probability of survival at one year compared to 26% (95% CI: 10%, 66%) for those with NLR ≥ 8. No statistically significant differences in probability of PFS at 1 year were seen between NLR < 8 compared to those with NLR ≥ 8 (p = 0.70). Conclusions: Pre-treatment NLR may hold prognostic value for patients with metastatic/recurrent cervical cancer treated with PD-1/PD-L1 inhibitors, with NLR < 8 associated with improved survival.

Beyond mismatch repair deficiency? Pre-treatment neutrophil-to-lymphocyte ratio is associated with improved overall survival in patients with recurrent endometrial cancer treated with immunotherapy.

OBJECTIVE: To determine the association of pre-treatment neutrophil-to-lymphocyte ratio (NLR) with progression-free survival (PFS) and overall survival (OS) for patients with recurrent endometrial cancer (EC) treated with immunotherapy. METHODS: Recurrent EC patients treated with immunotherapy alone or in combination from 2016 to 2021 were included. Demographics, pre-treatment laboratory results, pathologic data, response at first radiographic assessment, and cancer outcomes were obtained from the medical record. Kaplan-Meier curves were generated to compare PFS and OS stratified by NLR. RESULTS: The 106 patients included in the study were stratified by NLR <6 (n = 77, 72.6%) or NLR ≥6 (n = 29, 27.3%). Most had endometrioid pathology (59%), widely metastatic disease, and 36.8% had received ≥2 treatment lines before initiating immunotherapy. Mismatch repair deficiency (dMMR) was noted in 52 (49.1%) tumors. Most dMMR patients (94.3%) were treated with single-agent pembrolizumab, and most MMR proficient patients (78.7%) were treated with lenvatinb plus pembrolizumab. In the overall cohort, 40.2% (partial response (PR) 29.9%, complete response (CR) 10.4%) of patients with a NLR <6 responded at first radiographic assessment, compared to 31% (PR 27.5%, CR 3.4%) of patients with NLR ≥6 (p 0.691). Kaplan-Meier curves stratified by NLR <6 vs. ≥6 showed no difference in PFS. However, NLR <6 was associated with improved OS (p < 0.05). In the NLR < 6 group, the probability of survival at one year was 69% (95% CI: 58%, 82%), compared to 41% (95% CI: 26%, 67%) for the NLR > 6 group. CONCLUSIONS: Pre-treatment NLR <6 was associated with improved OS for recurrent EC patients treated with immunotherapy. NLR holds promise as a predictive biomarker for survival after immunotherapy treatment for patients with recurrent EC.

Evaluating hip disarticulation outcomes in a 51-patient series.

Background: Hip disarticulations are proximal lower extremity amputations with high postoperative complication and mortality rates. The purpose of the study was to evaluate hip disarticulation outcomes at our institution. Targeted Muscle Reinnervation (TMR) is an effective surgical technique shown to reduce pain in amputees. A secondary goal of the study was to evaluate the impact of implementing TMR on this patient population. Methods: A retrospective review was performed for patients who underwent hip disarticulation with and without TMR between 2009 and 2020. Information on one-year mortality, thirty-day complication rates, operation times, surgical charges, and pain scores was collected. Results: Fifty-one patients underwent hip disarticulation, eight of which had TMR performed at the time of their hip disarticulation. The one-year mortality rate was 37% with 30-day infection, readmission, reoperation, and rates of 37%, 39%, and 27% respectively. The thirty-day major complication rate was 47% overall but not statistically significantly different between groups. There were no differences between groups with regard to 30-day readmission, reoperation, and infection rates. Conclusions: Our results represent one of the largest series of hip disarticulation outcomes. Performing TMR at the time of hip disarticulation did not negatively affect outcomes and may be a beneficial adjunct to improve pain. Further research is warranted.

Cannabinoids in the Orthopedic Setting: A Literature Review.

Public interest in the analgesic potential of cannabinoids has grown, but there is no consensus regarding orthopedic applications. Available evidence was identified for cannabinoid use in arthritis, neuropathic pain, fibromyalgia, multiple sclerosis, and postoperative pain. Extracted information included the risks of preoperative use, associations with opioid dependence, and surgical complications. There is limited evidence for therapeutic benefit of cannabinoids in rheumatoid arthritis and fibromyalgia. Cannabinoids are not indicated for postoperative pain. Preoperative unregulated use has been linked with postoperative opioid dependence. Cannabinoids may be considered a second- or third-line treatment for analgesia for some orthopedic pathologies. [Orthopedics. 2022;45(4):e183-e189.].

Conserved ESX-1 Substrates EspE and EspF Are Virulence Factors That Regulate Gene Expression.

Mycobacterium tuberculosis, the cause of human tuberculosis, and Mycobacterium marinum, a nontubercular pathogen with a broad host range, require the ESX-1 secretion system for virulence. The ESX-1 system secretes proteins which cause phagosomal lysis within the macrophage via an unknown mechanism. As reported elsewhere (R. E. Bosserman et al., Proc Natl Acad Sci U S A 114:E10772-E10781, 2017, https://doi.org/10.1073/pnas.1710167114), we recently discovered that the ESX-1 system regulates gene expression in M. marinum This finding was confirmed in M. tuberculosis in reports by C. Sala et al. (PLoS Pathog 14:e1007491, 2018, https://doi.org/10.1371/journal.ppat.1007491) and A. M. Abdallah et al. (PLoS One 14:e0211003, 2019, https://doi.org/10.1371/journal.pone.0211003). We further demonstrated that a feedback control mechanism connects protein secretion to WhiB6-dependent expression of the esx-1 genes via an unknown mechanism. Here, we connect protein secretion and gene expression by showing for the first time that specific ESX-1 substrates have dual functions inside and outside the mycobacterial cell. We demonstrate that the EspE and EspF substrates negatively control esx-1 gene expression in the M. marinum cytoplasm through the conserved WhiB6 transcription factor. We found that EspE and EspF are required for virulence and promote lytic activity independently of the major EsxA and EsxB substrates. We show that the dual functions of EspE and EspF are conserved in the orthologous proteins from M. tuberculosis Our findings support a role for EspE and EspF in virulence that is independent of the EsxA and EsxB substrates and demonstrate that ESX-1 substrates have a conserved role in regulating gene expression.

A Team Disclosure of Error Educational Activity: Objective Outcomes.

Medical errors can involve multiple team members. Few curricula are being developed to provide instruction on disclosing medical errors that include simulation training with interprofessional team disclosure. To explore more objective evidence for the value of an educational activity on team disclosure of errors, faculty developed and assessed the effectiveness of a multimodal educational activity for learning team-based disclosure of a medical error. This study employed a methodological triangulation research design. Participants (N = 458) included students enrolled in academic programs at three separate institutions. The activity allowed students to practice team communication while: (1) discussing a medical error within the team; (2) planning for the disclosure of the error; and (3) conducting the disclosure. Faculty assessed individual student's change in knowledge and, using a rubric, rated the performance of the student teams during a simulation with a standardized family member (SFM). Students had a high level of preexisting knowledge and demonstrated the greatest knowledge gains in questions regarding the approach to disclosure (P < .001) and timing of an apology (P < .001). Both SFMs and individual students rated the team error disclosure behavior highly (rho = 0.54; P < .001). Most participants (more than 80%) felt the activity was worth their time and that they were more comfortable with disclosing a medical error as a result of having completed the activity. This activity for interprofessional simulation of team-based disclosure of a medical error was effective for teaching students about and how to perform this type of important disclosure.