Citations

Background Adductor canal block (ACB) is an alternative method to femoral nerve block (FNB) for post-operative analgesia for anterior cruciate ligament reconstruction (ACLR) in pediatric and adolescent patients. Prior studies have suggested that FNB is associated with persistent strength deficits at 6 months after ACLR in this population. Proponents of the ACB consider that this method may result in a decreased incidence of quadriceps strength deficits during post-operative rehabilitation. The purpose of this study was to compare knee strength and function at 6 and 9 months after ACLR in pediatric and adolescent patients who received FNB versus ACB peri-operatively. Methods Patients 18 years or younger who underwent primary ACLR between 2002 and 2017 at a single institution were identified. ACLR was performed with either a patellar tendon autograft or hamstring autograft. A transphyseal ACLR was performed in patients with open physes. All patients participated in a comprehensive rehabilitation program which included isokinetic strength testing and functional testing at 6 and/or 9 months postoperatively. Patients were excluded if they underwent multiligamentous knee reconstruction, concomitant cartilage restoration procedures, did not receive perioperative FNB or ACB, or if they did not complete isokinetic strength and functional testing at 6 or 9 months. The included cohort was separated into FNB group and ACB group for comparison. Isokinetic extension and flexion strength deficits and functional deficits in vertical jump, single hop, and triple hop between the two groups were compared at both time points. A strength deficit of 15% or less and a functional deficit of 10% or less compared to the contralateral side were considered satisfactory. Univariate analysis was performed to assess for differences in patient demographics and surgical variables. A 1:1 matched subgroup analysis between the two groups was performed to account for possible differences in outcomes associated to graft types, concomitant meniscus repair, and BMI. Results Of the 240 patients identified, 85 patients (64 FNB, 21 ACB) with a mean age of 15.9 years (Range: 11-18) met inclusion criteria for comparison at 6 months and 76 patients (40 FNB, 36 ACB) with a mean age of 15.5 years (Range: 12-17) met inclusion criteria for comparison at 9 months. Univariate analysis showed significantly greater deficits at 6 months in the FNB with respect to fast isokinetic flexion strength (7.7% vs. -4.9%; p = .03). There were no differences in slow isokinetic flexion (10.5% vs. 6.8%; p = .79) and fast isokinetic extension (11.9% vs. 13.9%; p = .68) strength deficits between the groups. There were clinically relevant greater deficits in the FNB group with respect to slow isokinetic extension (19.3% vs. 12.0%; p = .24), but this did not reach statistical significance. This clinical difference in satisfactory scores between the groups with respect to slow isokinetic extension was accentuated with the 1:1 matched outcome trial (23.9% vs. 12.1%; p = .20). With respect to function, there were no differences in deficits for vertical jump (8.4% vs. 4.3%; p = .55), single hop (7.4% vs. 9.3%; p = .65), or triple hop (6.0% vs. 7.1%; p = .77) between the two groups. Univariate analysis showed significant greater deficits at 9 months in the FNB with respect to slow isokinetic flexion strength (9.6% vs. 0.4%; p = .01). There were no differences in fast isokinetic flexion (-0.2% vs. 0.7%; p = .87) and fast isokinetic extension (6.0% vs. 2.7%; p = .51) strength deficits between the groups. There were clinically relevant greater deficits in the FNB group with respect to slow isokinetic extension (17.3% vs -14.0%, p = .19), but this did not reach statistical significance. With respect to function, there were no differences in deficits for vertical jump (5.2% vs. 6.5%, p = .85), single hop (7.7% vs. 6.2%; p = .79), or triple hop (1.9% vs. 3.9%; p = .35) between the two groups. Conclusion Because previous studies have shown a significant delay in return of strength with FNB, ACB began to be employed at our center for post-operative pain control following ACLR in pediatric and adolescent patients. This study showed that pediatric and adolescent patients treated with FNB as a method of post-operative analgesia after ACLR had significantly greater deficits in fast isokinetic flexion at 6 months and slow isokinetic flexion at 9 months compared to those who received ACB. These differences may or may not have clear clinical relevance. However, patients treated with FNB showed clinically relevant greater deficits in slow isokinetic extension strength at 6 and 9 months postoperatively compared to those who received ACB if 85% strength return is used as criteria to return to sport. Pediatric and adolescent patients could benefit from undergoing perioperative analgesia with ACB instead of FNB, but comparison between these two methods of regional anesthesia may require a prospective trial. Level of Evidence Retrospective cohort study, Level IV [Table: see text][Table: see text]

Background: The patient/caregiver experience during CAR-T therapy is stressful, overwhelming, terrifying, and often a patient’s last treatment option. The Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery Innovation and Design team has worked with the CAR-T therapy clinical team to develop a patient experience that provides patients with a sense of caring, supportive environment, timely knowledge, and realistic expectations. Using a human-centered design approach, the Innovation and Design team worked with patients and caregivers to understand latent and unspoken needs in order to develop an ideal CAR-T therapy patient journey. Methods: With qualitative interviewing techniques, patient observation, and low fidelity experimentation, 21 patients/caregiver pairs were interviewed throughout their CAR-T therapy experience in 2018. Patients were interviewed at several touch points as well as encouraged to reach out to the Innovation and Design team at any point with reflections on their experiences. Patients were recruited as they began their evaluation phase for CAR-T therapy. The interviews were unscripted to allow for a breadth of discovery by not constraining the conversations to previously developed themes. As themes emerged from patient/caregiver interviews, artifacts and interventions were designed to alleviate pain points and improve the patient/caregiver experience. These artifacts and interventions were integrated into the clinical processes in real time and patient/caregivers were interviewed to understand the impact of these activities. Results: Several themes emerged from qualitative interviews with patients and caregivers. From the themes, interventions were developed. We were able to demonstrate a qualitative improvement in patient/caregiver experience through these interventions (Figure 1). Conclusions: Patients/caregivers undergoing CAR-T therapy have unique issues surrounding the logistics of care, emotional burden, and physical effects of treatment. We implemented processes to address these issues and observed a qualitative improvement via patient interviews/feedback. Ongoing work includes optimizing remote monitoring, digital platforms for patient education, and a quantitative study looking at patient reported outcomes (PROs) in such patients. To our knowledge, this is the first report for care delivery optimization in real-world practice for this new therapy.

Background Steps towards the development of diagnostic criteria are needed for children with the radiologically isolated syndrome to identify children at risk of clinical demyelination. Objectives To evaluate the 2005 and 2016 MAGNIMS magnetic resonance imaging criteria for dissemination in space for multiple sclerosis, both alone and with oligoclonal bands in cerebrospinal fluid added, as predictors of a first clinical event consistent with central nervous system demyelination in children with radiologically isolated syndrome. Methods We analysed an international historical cohort of 61 children with radiologically isolated syndrome (≤18 years), defined using the 2010 magnetic resonance imaging dissemination in space criteria (Ped-RIS) who were followed longitudinally (mean 4.2 ± 4.7 years). All index scans also met the 2017 magnetic resonance imaging dissemination in space criteria. Results Diagnostic indices (95% confidence intervals) for the 2005 dissemination in space criteria, with and without oligoclonal bands, were: sensitivity 66.7% (38.4–88.2%) versus 72.7% (49.8–89.3%); specificity 83.3% (58.6–96.4%) versus 53.9% (37.2–69.9%). For the 2016 MAGNIMS dissemination in space criteria diagnostic indices were: sensitivity 76.5% (50.1–93.2%) versus 100% (84.6–100%); specificity 72.7% (49.8–89.3%) versus 25.6% (13.0–42.1%). Conclusions Oligoclonal bands increased the specificity of magnetic resonance imaging criteria in children with Ped-RIS. Clinicians should consider testing cerebrospinal fluid to improve diagnostic certainty. There is rationale to include cerebrospinal fluid analysis for biomarkers including oligoclonal bands in planned prospective studies to develop optimal diagnostic criteria for radiologically isolated syndrome in children.

PURPOSE The mode of action of targeted cancer agents (TCAs) differs from classic chemotherapy, which leads to concerns about the role of RECIST in evaluating tumor response in trials with TCAs. We investigated the performance of RECIST using a pooled database from 50 clinical trials with at least one TCA. METHODS We examined the impact of the number of target lesions (TLs) on within-patient variability of tumor response. The prognostic effect of TL response (at 12 weeks or on study on the basis of a maximum five TLs) on survival was studied through landmark and time-dependent Cox models adjusted for baseline tumor load, occurrence of new lesions, or unequivocal progression of nontarget disease. RESULTS Data were obtained from 23,259 patients with cancer (36% lung, 28% colorectal, 11% breast, and 25% other); 15,620 received TCAs, predominantly transduction or angiogenesis inhibitors, as a single agent (37%), combined with other TCAs (7%), or as chemotherapy (56%); 28% received chemotherapy only; and 5% received best supportive care or placebo. A total of 17,222 patients contributed to the analyses. Within-patient variability decreased with increasing number of TLs, similarly for TCAs (with/without chemotherapy) and chemotherapy only. Mixed responses occurred proportionally in all treatment classes. Landmark analyses showed an ordinal relationship between percentage change from baseline to 12 weeks and overall survival, and demonstrated a clear distinction between tumor shrinkage and progressive disease according to RECIST. Time-dependent analysis showed no marked improvement in the ability to predict survival on the basis of TL tumor growth compared with nontarget progression or new lesion occurrence, regardless of treatment. Similar results were seen for major tumor types and different classes of TCAs. CONCLUSION This work reinforces that RECIST version 1.1 perform well for response assessment of TCAs.

PURPOSE Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)–positive breast cancer to the CNS are limited. We previously reported modest activity of neratinib monotherapy for HER2-positive breast cancer brain metastases. Here we report the results from additional study cohorts. PATIENTS AND METHODS Patients with measurable, progressive, HER2-positive brain metastases (92% after receiving CNS surgery and/or radiotherapy) received neratinib 240 mg orally once per day plus capecitabine 750 mg/m 2 twice per day for 14 days, then 7 days off. Lapatinib-naïve (cohort 3A) and lapatinib-treated (cohort 3B) patients were enrolled. If nine or more of 35 (cohort 3A) or three or more of 25 (cohort 3B) had CNS objective response rates (ORR), the drug combination would be deemed promising. The primary end point was composite CNS ORR in each cohort separately, requiring a reduction of 50% or more in the sum of target CNS lesion volumes without progression of nontarget lesions, new lesions, escalating steroids, progressive neurologic signs or symptoms, or non-CNS progression. RESULTS Forty-nine patients enrolled in cohorts 3A (n = 37) and 3B (n = 12; cohort closed for slow accrual). In cohort 3A, the composite CNS ORR = 49% (95% CI, 32% to 66%), and the CNS ORR in cohort 3B = 33% (95% CI, 10% to 65%). Median progression-free survival was 5.5 and 3.1 months in cohorts 3A and 3B, respectively; median survival was 13.3 and 15.1 months. Diarrhea was the most common grade 3 toxicity (29% in cohorts 3A and 3B). Neratinib plus capecitabine is active against refractory, HER2-positive breast cancer brain metastases, adding additional evidence that the efficacy of HER2-directed therapy in the brain is enhanced by chemotherapy. For optimal tolerance, efforts to minimize diarrhea are warranted.

HIV-1 infections usually start at a mucosal surface after sexual contact. Creating a barrier of protection at these mucosal sites may be a good strategy for to protect against HIV-1 infections. While HIV-1 enters at mucosa, most vaccines are not delivered here. Most are instead injected into the muscle, a site well distant and functionally different than mucosal tissues. This study tested if delivering HIV vaccines at mucosa or in the muscle makes a difference in the quality, quantity, and location of immune responses against the virus. These data suggest that there are indeed advantages to educating the immune system at mucosal sites with an HIV-1 vaccine.