Citations

592 Background: While not all fevers occurring during hematopoietic stem cell transplantation (HCT) are dangerous, episodes of febrile neutropenia tend to be managed aggressively given the significant mortality and morbidity associated with infectious complications of transplantation. This can potentially lead to unnecessary diagnostic testing, antibiotic treatment, and prolonged hospital stays for non-infectious fever etiologies such as engraftment. Our group has previously demonstrated that high-frequency body temperature monitoring (HFTM) using a wearable device detects fevers earlier in transplant recipients (Flora et al, Cancer Cell, 2021). We hypothesized that applying supervised machine learning to HFTM data collected from inpatient allogeneic HCT patients would allow for accurately distinguishing between non-infectious and infectious etiologies of fever and could potentially guide safe de-escalation of antibiotics. Methods: We analyzed 74 independent fever events detected in HCT patients (n=42) outfitted with an FDA-cleared, wireless sensor measuring axillary temperatures every 2 minutes for the duration of their respective hospitalizations. After data filtering, independent fever events were then retrospectively grouped by fever etiology using physician-determined annotation as previously described (Flora et al., 2021). A split ratio of 80:20 was used to create training and test sets from the parent data set, consisting of 59 and 15 fever events for each split, respectively. Training sets were used to create a classification algorithm identifying bacterial infections requiring antibiotics using the machine learning model XGBoost. The performance of this model was then evaluated using test sets of the remaining fevers (n=15). Results: Averaging over 1000 test sets of 15 independent fevers comprising 5 bacterial infection-related fevers and 10 non-infectious fevers, our model correctly identified 82% (mean recall) of cases requiring antibiotics with a mean precision of 0.41. The model also correctly identified 42% of non-infectious fevers (mean true negative rate, 0.42) that would otherwise have been treated with unnecessary antibiotics. The mean AUCPR was 0.58, with the best performing individual model achieving an AUCPR of 0.97. Conclusions: The preliminary results of this study demonstrate that our classification model shows promise for differentiating fevers requiring antibiotics due to bacterial infections from other non-infectious fever etiologies. Prospective studies further developing supervised machine learning models for subcategorization of febrile neutropenia could pave the way for safely de-escalating antibiotics in HCT and other immunocompromised patients undergoing cancer treatment monitored using HFTM.

Background: Chronic nonspecific low back pain (CNLBP) is a prevalent, disabling condition worldwide. Tuina, a traditional Chinese manual therapy, has shown potential benefits, but evidence remains limited. Objective: This study evaluated the effectiveness and safety of Tuina therapy in managing CNLBP in a U.S. population. Methods: A prospective, single-blind, randomized controlled trial was conducted at Mayo Clinic Rochester campus (February 2020-April 2024). 204 participants with CNLBP were randomized into 3 groups: Tuina (N = 68), physical therapy (N = 68), or a combination of both (N = 68). Each group received 6 treatments over 2 months. The primary outcome was pain intensity (VAS); secondary outcomes included disability (ODI), quality of life (SF-36), and adverse events. Additionally, participants completed a satisfaction survey at the end of the trial. Research Electronic Data Capture (REDCap) was used for survey data collection. Data was assessed by analysis of variance (ANOVA) for the multiple repeated measurements, Kruskal-Wallis tests, while Chi-square tests, and Bonferroni correction in SAS software. Results: 185 subjects completed the study. Significant decreases in VAS, ODI, and SF-36 Overall Physical scores were found from baseline, to post treatment and follow-up in all groups ( P < .05), while there were no significant differences in VAS, ODI, or SF-36 outcomes between the Tuina group and the other 2 groups. There were 4 adverse events observed in the trial, 1 in the Physical therapy group and 3 in the Mixed group. Only 1 transient low back pain after Tuina therapy was observed in the Mixed group but did not require treatment. The high percentage of patients who received the Tuina program was extremely helpful (n = 94/126, 77.0%). The willingness to recommend was significantly higher for Tuina compared to physical therapy (Mixed group [N = 59/62, 95.2%], Tuina group [N = 57/64, 91.9%], and physical therapy group [N = 31/59, 59.6%] ( P < .05). Conclusion: Tuina therapy showed comparable benefits to physical therapy and combined treatment of both in improving pain, function, and quality of life in patients with CNLBP. With high patient satisfaction and a favorable safety profile, Tuina appears to be a safe and acceptable non-invasive treatment option. Further studies are needed to validate these findings in the future.

Abstract BACKGROUND Ovarian cancer rarely metastasises to the brain, thus studies reporting the outcomes of affected patients are lacking. Stereotactic radiosurgery (SRS) is now the mainstay of management for patients with brain metastases (BM) from most primary sites, but little evidence of its efficacy in ovarian cancer is available. The current study was undertaken to provide guidance for SRS management using pooled data from multiple institutions. MATERIAL AND METHODS Centers participating in the IRRF (International Radiosurgery Research Foundation) were asked to provide outcome data for patients who had SRS for ovarian cancer brain metastases between 2020 and 2024 and at least one clinical and imaging follow-up after the procedure. Primary endpoints included survival from SRS, local tumor response according to RANO-BM criteria and occurrence of adverse radiation effects (ARE). Cox regression analyses were performed to identify variables impact each endpoint. RESULTS 128 patients had SRS for a total of 532 BM treated. Epithelial histology was the most common (91%). Median age at SRS was 62 years (IQR 56-70). Median KPS was 80% (IQR 80-90%) and 71.9% of patients had neurological symptoms at presentation. Other active systemic metastases were present in 41.4%. The median number of treated BM was 2 (IQR1-3) and the median cumulative treatment volume was 6 cc (IQR 2-12.9). The median margin dose was 18 Gy (IQR 16-20). At last follow-up, 19.5% of patients were still alive. The median overall survival (OS) after SRS was 27 months, and 6-, 12- and 24-month OS was 83.8%, 74.2% and 52.2%, respectively. Multivariate analyses revealed that increasing age at SRS (HR 1.02, p=0.05), active systemic metastases (HR 2, p=0.005) and increasing number of brain metastases (HR 1.05, p=0.04) were associated with worse survival, while repeating SRS (HR 0.4, p=0.002) led to improved survival. Local failure occurred in 12.8% of treated BM. Actuarial progression-free survival (PFS) at 6, 12 and 24 months was 92.3%, 86.6% and 70.3%, respectively. Only prior WBRT (HR 4.36, p=0.03) led to worse local control on multivariate analyses. New remote BM appeared in 49.5% of patients and 14.5% suffered from leptomeningeal dissemination. ARE were seen in 12.1% of BM but were symptomatic in only 3.2%. On multivariate analyses, prior SRS (HR 3.13, p=0.002) was associated with increased risk of ARE. CONCLUSION Ovarian cancer brain metastases can be safely and effectively managed with SRS as the primary treatment modality in most patients.

Abstract The acetabular labrum is a fibrocartilaginous structure that deepens the acetabular socket and helps maintain a suction seal. In patients with hip dysplasia, a distinct labral tear pattern called an inside‐out labral tear is often seen. This tear pattern is particularly challenging to correct via conventional techniques since the labrum can potentially remain everted and insufficiently restore the native hip labral suction seal after repair. An inverted hip labral repair technique is performed for this pathology at our institution and focuses on achieving optimal labral orientation to enhance the suction seal and joint stability, particularly in dysplastic hips. This Technical Note aims to describe the key surgical principles and clinical considerations of inverted hip labral repair. Technique Video video See video under supplementary data.

Objectives: Historically, horizontal cleavage meniscus tears have been debrided with single leaflet preservation, but more recently this has been challenged by repair of these tear types. While circumferential meniscus repair with all-inside and inside-out instrumentation has been described, there remains a paucity of literature regarding the clinical outcomes of this technique. Our purpose was to assess clinical outcomes and reoperation rates of circumferential meniscus repair for horizontal cleavage tears at minimum 2-year follow-up. Methods: Patients with isolated horizontal cleavage tears of the meniscus (Fig. 1a) undergoing primary circumferential meniscus repair (Fig. 1b), including both inside-out and all-inside suturing techniques, at a single institution between 2015 and 2022 were eligible for inclusion and analyzed retrospectively. Arthroscopic images and operative notes were examined to confirm circumferential meniscal repair. Patient demographics, surgery details, and clinical findings were extracted from the institutional electronic medical records. Exclusion criteria consisted of patients not consenting for research, less than 2-years of clinical follow-up, and concurrent ipsilateral repair of a non-horizontal cleavage tear. Patients were not excluded if they had a concomitant anterior cruciate ligament reconstruction (ACLR). Thirty-seven patients met the criteria for inclusion in this study. Knees were analyzed for laterality, number of sutures, suturing technique, concurrent injuries, concurrent procedures, and surgical history. Visual Analogue Scale (VAS) for pain, Tegner, and International Knee Documentation Committee (IKDC) scores were collected at minimum 2-year follow-up and analyzed. Return to sport (RTS) and revision surgery were analyzed. Results: Thirty-seven patients (25 male, 12 female; mean age, 29.4 ± 12.4 years) who underwent circumferential meniscal repair of a horizontal cleavage tear were included in the study and followed for a mean of 6.2 years (range, 2.2-9.3 years, Table 1). There was a total of 38 knees (23 right, 15 left). One patient (3%) had bilateral circumferential meniscal repair surgeries done at separate times. Three (16%) patients failed primary repair and had secondary partial meniscectomy. Similar numbers of circumferential meniscal repairs were performed on lateral and medial menisci, 21 (55%) and 17 (45%), respectively. An average number of 3 ± 2 sutures were used at the time or repair with one of 38 menisci (3%) having a hybrid combination of both all-inside and inside-out suture technique, 24 menisci (63%) had all-inside technique, and 13 menisci (34%) had inside-out technique. Concurrent procedures included 4 ACL reconstructions (3 autograft, 1 allograft), and 8 chondroplasties (4 patella, 2 trochlea, 1 medial femoral condyle, and 1 unspecified, Table 2). At the time of final follow-up, patients reported mean Tegner activity scores of 6.2 ± 2.3, VAS pain with rest of 1.0 ± 2.0, VAS pain with use of 2.5 ± 2.7, and IKDC of 81.6 ± 18.6. When asked, using a VAS Five Point scale, how their knee is currently compared to before their surgery, 14 (74%) feel much better than before surgery, 2 (11%) feel slightly better than before surgery, 1 (5%) feels no change when compared to before their surgery, 2 (11%) feel slightly worse than before surgery, and no one felt much worse than before surgery. Sixteen patients were involved in sports before their surgery. Of those that played sports before their surgery, 14 (88%) returned to sport (Table 3). The most common sports played were hockey (19%), volleyball (19%), tennis (13%), and football (13%). Levels of sport played before surgery included 7 (44%) recreational, 6 (38%) high school, 2 (13%) college, and 1 (6%) club. Levels of sport played after surgery for those who returned to sport included 6 (43%) recreational, 2 (14%) high school, 5 (36%) college, and 1 (7%) club with a significant increase in levels of sport played after surgery ( p ≤ 0.006) compared to before surgery. Conclusions: At an average of 6-years of follow up, there was an 84% success rate of circumferential meniscal repair for horizontal cleavage tears. Most patients who play sports, return to sport and do so at the same or higher level and report successful PROMs. Circumferential meniscal repairs should be considered for patients with horizontal cleavage tears.

The clinical benefit of blood transfusion is undeniable, and yet reliance on donated blood products has several shortcomings. These include risks of supply shortages due to reliance on volunteer donors, short storage life, and potential infectious disease transmission. Immune response complications to donated blood cannot be completely avoided, despite significant advances in testing. Many of these limitations are exacerbated in low-income countries. For decades, cell-free hemoglobin-based blood substitutes have been developed and tested as potential substitutes for red blood cell transfusions. Early studies found that purified, native hemoglobin exhibited significant safety risks, such as hypertension from excessive vasoconstriction and evidence of multiple organ toxicities. These effects are likely in part due to the reactive heme center, which will scavenge nitric oxide, generate reactive oxygen species, and may drive sterile inflammation. Numerous strategies have been explored to further modify hemoglobin in the hope of creating a safe and well-tolerated blood substitute. Despite some promising results in preliminary studies, large-scale clinical trials have continued to show elevated rates of adverse events and/or a failure to meet specified clinical endpoints. As a result, no hemoglobin-based oxygen carrier (HBOC) has obtained US Food and Drug Administration approval for clinical use. This review focuses on the history of HBOC development, the lessons that have been learned from prior failures of HBOC programs, and the status of ongoing artificial oxygen carrier development efforts.