6-week Course Research Articles

Abstract PO1-19-06: Physical exercise during neoadjuvant chemotherapy for breast cancer as a mean to increase pathological complete response rates: the randomized Neo-ACT trial

Abstract Introduction In early breast cancer, neoadjuvant chemotherapy (NACT) is increasingly used. The proof of efficacy is pathologically complete response (pCR), i.e. the absence of invasive tumour in breast and lymph nodes at surgery. Today, pCR is a common endpoint in pharmaceutical trials since it is significantly associated with survival especially in triple-negative and HER2-positive subtypes. Apart from the mitigation of treatment-related toxicity and symptoms, physical exercise mediates anti-tumoral systemic effects associated with tumour regression in preclinical and clinical models. The aim of Neo-ACT is to test the hypothesis that physical exercise can improve pCR rates in breast cancer patients receiving NACT. Method The Neo-ACT trial is an international prospective clinical trial, randomising T1-3N0-2 breast cancer patients planned for NACT to either a home-based physical exercise intervention supported by a mobile application or routine care. The primary endpoint is pCR; secondary endpoints are patient-reported quality of life, toxicity-related outcomes, and oncological outcomes such as Residual Cancer Burden, objective radiological tumour response, as well as overall, breast cancer-specific and disease-free survival at 2, 5 and 10 years. The intervention consists of a combination of high-intensity interval and resistance training of progressing intensity, and includes two weekly 60-min exercise sessions plus at least 150 min of moderate to vigorous physical activity per week. The Neo-ACT has been registered at clinicaltrials.gov on January 11, 2022 (NCT05184582). Statistical methods Patients will be randomized in a 1:1 fashion. It is anticipated that the rate of the primary endpoint pCR will be approximately 30% in the control arm (all subtypes). We aim to increase the rate of pCR in the experimental arm to 40%, i.e. a 10 percentage points increase, which is regarded clinically relevant since it would translate into improved disease-related outcomes. With a power of 80% and an alpha of 5%, a total of 712 patients have to be included; 356 in each arm. Accounting for a drop-out of 10%, we aim to include 790 patients. Stratification at the moment of computerized randomization is based on site of treatment (hospital) and biological tumour subtype (ER+HER2-, ER+HER2+, ER-HER2+, ER-HER2-). All outcomes will primarily be analysed using an intention-to-treat approach, i.e. all study subjects will belong to the treatment group (exercise intervention or control) they were assigned to, disregarding compliance. As sensitivity analysis, all outcomes will also be analysed using a per-protocol approach, meaning that participants in the intervention group who comply with less than 65% of the prescribed physical exercise program, and participants who complete less than 40% of the planned neoadjuvant systemic therapy (around two 3-weekly courses) will be excluded from analysis. Present accrual The Neo-ACT trial has started enrolment at the first site in December 2022 and since then initiated a further five Swedish and one Finnish site. Until June 15, 2023, 26 participants had been randomized in the trial. A feasibility questionnaire is distributed via the EUBREAST network which officially supports this trial and has added the designation EUBREAST12-R. Further participating sites can be accommodated depending on volume, competing trials and language requirements for the mobile application. Contact: jana.de-boniface@ki.se Citation Format: Jana de Boniface, Cecilia Haddad Ringborg, Renske Altena, Yvonne Wengström. Physical exercise during neoadjuvant chemotherapy for breast cancer as a mean to increase pathological complete response rates: the randomized Neo-ACT trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-19-06.

Pomegranate polyphenol punicalin ameliorates lipopolysaccharide-induced memory impairment, behavioral disorders, oxidative stress, and neuroinflammation via inhibition of TLR4-NF-кB pathway.

Neuroinflammation may play an important role in the development of Alzheimer's disease (AD). Previous studies have reported that lipopolysaccharide (LPS)-induced neuroinflammation causes memory impairments and behavioral disorders. We investigated the potential preventive effects of punicalin (PUN), a polyphenolic component of pomegranate, on LPS-induced memory deficiency and anxiety- and depression-like behaviors, along with the underlying mechanisms. LPS-treated cultured microglial BV2 cells and BV2 cell/Neuro-2a (N2a) cell coculture system were investigated for anti-neuroinflammatory effects of PUN in vitro. The in vivo experiments involved mice administered a 4-week course of oral gavage with 1500 mg/kg/d PUN before intraperitoneal LPS (250 mg/kg daily 7 times) injections. The in vitro results demonstrated that PUN inhibited the LPS-induced inflammatory cytokine (IL-18, IL-1β, TNF-ɑ, and IL-6) production in BV2 cells and protected N2a cells from synaptic damage mediated by BV2 microglia-induced neuroinflammation. In in vivo studies, it was observed that PUN improved memory impairment and anxiety- and depression-like behaviors caused by LPS and reduced the expression of inflammatory proteins such as iNOS, COX-2, IL-1β, IL-2, IL-6, and TNF-α. Furthermore, PUN inhibited the LPS-induced production of MDA; increased the activities of CAT, SOD, and GSH-Px, and inhibited LPS-induced Aβ1-42 generation through down-regulation of APP and BACE1 expression. Moreover, PUN also suppressed the expression of TLR4, IRAK4, TRAF6, IKK-β, NF-κB, p65, and HMGB1 in LPS-treated mouse brain and cultured microglial BV-2 cells. These results suggest that PUN inhibits LPS-induced memory impairment via anti-inflammatory and anti-amylogenic mechanisms through inhibition of TLR4-NF-kB activation.

Abstract PO1-15-09: Vitamin A Metabolism Induces Ferroptosis to Enhance Immune Therapy Efficacy in HR+/HER2- Breast Cancer

Abstract Background: Immune checkpoint blockade (ICB) has substantially improved patient overall and progression-free survival in triple-negative breast cancer (TNBC), but its efficacy remains to be elucidated in the hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, which is characterized by generally impotent lymphocytic infiltration. In the I-SPY2 trial (NCT01042379), pembrolizumab- or durvalumab-containing neoadjuvant therapy increased the pathologic complete response of HR+/HER2- patients. However, pembrolizumab-containing therapy failed to improve the survival of metastatic HR+/HER2- breast cancer patients (NCT03051659). These inconsistent results underscored the necessity of the investigation of predictive biomarkers to pinpoint potential ICB responders in HR+/HER2- breast cancer. Method: In this study, we collected pretreatment tumor samples from 16 patients in two respective clinical trials (NCT: 04215003 and 04355858) and profiled droplet-based single-cell sequencing, bulk RNA-Seq. Patients were treated with camrelizumab (PD-1 inhibitor)-containing therapy, and five of them achieved partial relief after an 8-week course. We also leveraged the bulk RNA-Seq data from the I-SPY2 trial and Fudan University Shanghai Cancer Center (FUSCC) TNBC ICB trials (NCT04418154 and NCT04613674) for external validation. Another FUSCC transcriptome dataset consisting of 933 treatment-naïve HR+/HER2- or TNBC breast cancer patients was used to detect the abundance of cell types. In vitro and in vivo experiments were used to explore mechanisms of anti-tumor immune response. Results: Based on the single-cell sequencing results, we comprehensively delineated the microenvironmental landscape of HR+/HER2- breast cancer. We discovered responders of immunotherapy showed a higher presence of CXCL9/10+ M1-like macrophages and exhibited enrichment of tumor cells with ferroptosis. We further identified the upregulation of vitamin A metabolism and the vitamin A metabolic gene CRABP1 in tumor cells with ferroptosis. We verified the vitamin A metabolism could induce ferroptosis in HR+/HER2- breast cancers rather than TNBC by CRABP1-ERK axis, which could further recruit CXCL9/10+ M1-like macrophages and promote anti-tumor immune response in HR+/HER2- breast cancer. Combining anti-PD1 with enhancing vitamin A metabolism via retinoid acid possessed greater therapeutic efficacy than monotherapy in HR+/HER2- breast cancers. Finally, we developed an immune therapy response score and validated its reliability in predicting the immunotherapy efficacy for HR+/HER2-breast cancers through both internal and external cohorts. Conclusion: Our study represents the earliest efforts to decipher the microenvironmental landscape and the mechanisms underlying the response to ICB in HR+/HER2- breast cancer at single-cell resolution. We unraveled a HR+/HER2- breast cancer-specific Vitamin A-ferroptosis axis that mediated immunotherapy response and constructed a robust immunotherapy efficacy prediction score based on this Vitamin A-ferroptosis axis. Citation Format: Yi-Fan Zhou, Hu-Yun-Long Zhang, Xi Jin, Yi-Zhou Jiang, Zhi-Ming Shao. Vitamin A Metabolism Induces Ferroptosis to Enhance Immune Therapy Efficacy in HR+/HER2- Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-09.

Meeting summary: Exploring cloud dynamics with Cloud Model 1 and 3D visualization – insights from a university modeling workshop

Abstract. We introduce an innovative 2-week educational block course held at the University of Bonn during the 2023 winter semester, focusing on Cloud Model 1 (CM1) and its convection-resolving capabilities. During the course, participants gained essential skills in setting up and customizing CM1 simulations on a high-performance computing cluster while gaining insights into moist-convection dynamics. An additional introduction to three-dimensional visualization software allowed the participants to transform numerical data into compelling visualizations, deepening their insights into cloud dynamics. The participants applied their gained knowledge in research projects of their own choice that will be presented here and in the Supplement.

Abstract 3047: Extracellular Vesicles Produced By IL4-polarized Human Macrophages Suppress Atherosclerosis By Reprograming Ly6c hi Monocytes

Introduction: Extracellular vesicles (EVs) produced by IL4-polarized macrophages (Mφ) suppress inflammation by communicating microRNA-controlled immunometabolic signaling to recipient immune cells and adipocytes. However, detailed cellular and molecular pathways responsible for these effects remain incompletely understood. Objectives: Examine transcriptional responses sensitive to IL4-polarized Mφ EVs among circulating Ly6C hi monocytes derived from mice with hyperlipidemia. Methods/Approach: EVs were produced by culturing THP1 macrophages with human IL4, and purified using cushioned-density gradient ultracentrifugation. Twenty-week old male LDL-receptor deficient mice fed high-fat diet for 16 weeks were treated to a 6-week course of 3-weekly intraperitoneal infusions of 10e 10 THP1-IL4 EVs or sham. Circulating Ly6C hi monocytes were collected using a cell sorter and RNA was examined using nanoString nCounter inflammatory and metabolic pathway panels. Plasma cytokines were detected with a V-Plex MesoScale assay, while atherosclerosis was assessed by detecting myeloid cell subsets in enzymatically-digested aortae and oil red O positive lesions in the aortic root. Results: THP1-IL4 EVs caused profound transcriptional reprogramming among Ly6C hi monocytes, resulting in reduced signaling pathways controlled by MAPK, PI3K, TLR and inflammasomes. We identified reduced levels of Casp-1, Nlrp1a, as well as Aim2, all recognized to drive atherosclerosis including in JAK2 vf clonal hematopoiesis. Furthermore, THP1-IL4 EVs upregulated metabolic pathways involved in arginine metabolism, IDH1/2 activity, redox stress control, nucleotide salvage, fatty acid oxidation and mitochondrial respiration. In contrast they reduced pathways involved in glucose transport, hypoxia, KEAP-NRF2 pathway and tryptophan metabolism. Control of these pathways in Ly6C hi monocytes contributed to reduced levels of IL-1β, IL-6, IFNγ and TNFα in plasma, as well as CD45 + aortic myeloid cells and oil red O positive aortic lesions. Conclusions: IL4-polarized Mφ EVs suppress atherosclerosis by communicating profound transcriptional reprogramming to Ly6C hi monocytes. Ongoing studies examine their capacity to drive atherosclerosis regression.

Pulmonary rehabilitation in Iranian outpatients with mustard gas lung disease: a randomised controlled trial

ObjectivePeople with mustard gas lung disease experience cough, sputum, breathlessness and exercise limitation. We hypothesised that pulmonary rehabilitation (PR) would be beneficial in this condition.DesignAn assessor-blind, two-armed, parallel-design randomised controlled...

Repetitive transcranial magnetic stimulation can improve negative symptoms and/or neurocognitive impairments in the first psychosis episode: A randomized controlled trial

ObjectiveNegative symptoms and neurocognitive impairments in psychosis correlate with their severity. Currently, there is no satisfactory treatment. We aimed to evaluate and compare the effects of repetitive transcranial magnetic stimulation(rTMS) on negative symptoms and neurocognitive impairments in patients in first-episode of psychosis(FEP) in a randomized controlled trial(RCT). MethodThis is a single-site RCT of 85 patients with FEP. Patients were randomized to receive a 4-week course of active(n = 45) or sham rTMS(n = 40). Factor analysis was applied to a cross-sectional dataset of 744 FEP patients who completed negative symptom evaluation and neurocognitive battery tests. Two independent dimensions were generated and used for the K-means cluster analysis to produce sub-clusters. rTMS of 1-Hz was delivered to the right orbitofrontal(OFC) cortex. ResultsTwo distinct dimensional factors of neurocognitive functions(factor-1) and negative symptoms(factor-2), and three clusters with distinctive features were generated. Significant improvements in factor-1 and factor-2 were observed after 4-weeks of rTMS treatment in both the active and sham rTMS groups. The repeated-measures analysis of variance revealed a significant effect of time×group(F = 5.594, p = 0.021, η2 = 0.073) on factor-2, but no effect of time×group on factor-1. Only improvements in negative symptoms were significantly different between the active and sham rTMS groups(p = 0.028). Patients in cluster-3 characterized by extensive negative symptoms, showed greater improvement in the active rTMS group than in the sham rTMS group. ConclusionsThe 1-Hz right OFC cortex rTMS is more effective in reducing negative symptoms than neurocognitive impairments. It is especially effective in patients with dominantly negative symptoms in FEP.

The effectiveness of a short course to improve coaches’ knowledge on considerations for female athletes

ABSTRACT This study aimed to assess the effectiveness of an online short course in improving the knowledge and confidence of coaching and support staff when working with female athletes. A mixed-methods survey design was used, where participants completed surveys pre-, post-, and 6 months following an 8-week online course. Qualitative responses were analysed inductively using thematic analysis based on two pre-identified themes. Of the 92 participants who completed both pre- and post-course surveys, 72% (n = 66) were female and 67% (n = 62) were from team sports. Perceived knowledge and confidence improved following the course (p < 0.001) and were above pre-course values 6-months post (p < 0.001). A-priori theme Course Expectations generated two sub-themes: ’Empowering [me] to empower and support [them]’, and “Sharing knowledge and experiences”. A-priori theme Changes in Practice had subthemes of “Relaxing into it” and “Embedding support structures”. Participants indicated that they enjoyed learning from a variety of content experts as well as other participants in an online format. Future courses aimed at coaching/support staff should design and deliver accessible programs aligned with the learning preferences of these individuals. When delivering specific education regarding supporting female athletes, targeting and encouraging men to participate may be beneficial.

Feasibility, Acceptability, and Potential Efficacy of a Mobile Health Application for Community-Dwelling Older Adults with Frailty and Pre-Frailty: A Pilot Study.

Smartphone applications aimed at enhancing physical, cognitive, and social activities through mobile health (mHealth) technology are of increasing interest. Their feasibility and acceptability, alongside impacts on frailty phenotype scores and step counts among older adults with frailty, remain to be fully validated. This study presents a 13-week preliminary intervention trial assessing an mHealth app's feasibility in a cohort of 34 eligible older adults, including 5 frail and 29 pre-frail participants. The intervention entailed a 6-week course on app usage, followed by 7 weeks of observation, with four participants withdrawing early. Feasibility was determined by login and active use rates, with a target login rate of 60% or higher. Post-intervention, 100% session attendance and a median login rate of 88.4% were observed. Acceptability was high, with 73% affirming the app's health benefits. Notably, frailty scores and step counts improved post-intervention, underscoring the app's potential for supporting older adults with frailty.

LSD increases sleep duration the night after microdosing

Microdosing psychedelic drugs at a level below the threshold to induce hallucinations is an increasingly common lifestyle practice. However, the effects of microdosing on sleep have not been previously reported. Here, we report results from a Phase 1 randomized controlled trial in which 80 healthy adult male volunteers received a 6-week course of either LSD (10 µg) or placebo with doses self-administered every third day. Participants used a commercially available sleep/activity tracker for the duration of the trial. Data from 3231 nights of sleep showed that on the night after microdosing, participants in the LSD group slept an extra 24.3 min per night (95% Confidence Interval 10.3–38.3 min) compared to placebo—with no reductions of sleep observed on the dosing day itself. There were no changes in the proportion of time spent in various sleep stages or in participant physical activity. These results show a clear modification of the physiological sleep requirements in healthy male volunteers who microdose LSD. The clear, clinically significant changes in objective measurements of sleep observed are difficult to explain as a placebo effect. Trial registration: Australian New Zealand Clinical Trials Registry: A randomized, double-blind, placebo-controlled trial of repeated microdoses of lysergic acid diethylamide (LSD) in healthy volunteers; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381476; ACTRN12621000436875.

Sequential endoluminal gemcitabine and docetaxel vs. Bacillus Calmette–Guérin for the treatment of upper tract carcinoma in situ

IntroductionNephroureterectomy is commonly performed for high-grade (HG) upper tract (UT) urothelial carcinoma (UC). However, some patients may benefit from a de-escalation of surgical management, particularly for noninvasive disease and carcinoma in situ (CIS). Bacillus Calmette–Guerin (BCG) is currently the only guideline-recommended endoluminal treatment option. Gemcitabine/Docetaxel (Gem/Doce) has shown promising efficacy as a treatment for noninvasive HG UTUC, though a comparison to BCG is lacking. We report the outcomes of patients treated with endoluminal Gem/Doce vs. BCG for UT-CIS. MethodsA single-institutional retrospective review of patients treated with Gem/Doce vs. BCG for UT-CIS was performed. Treatment was instilled via nephrostomy or retrograde ureteral catheter. In both treatment groups, induction consisted of 6 weekly instillations. Maintenance was initiated if disease-free and consisted of 6 monthly instillations in the Gem/Doce group and a reduced dose (one-tenth) 3-week course at 3 months in the BCG group. Recurrence was defined as biopsy-proven disease or HG cytology. ResultsThe final cohort included 53 patients with 65 upper tract units; 31 received BCG and 34 received Gem/Doce. Median follow-up was 88 and 29 months in the BCG and Gem/Doce groups, respectively. Presenting pathology included biopsy-proven CIS and HG cytology in 9.7% and 90% of the BCG group, and 8.8% and 91% of the Gem/Doce group, respectively. The 2-year estimates for recurrence-free and nephroureterectomy-free survival were 61% and 89% for the BCG group and 54% and 100% for the Gem/Doce group, respectively. Upon multivariable analysis, instillation via percutaneous nephrostomy tube was associated with an increased risk of recurrence (HR 3.89, 95% CI 1.59–9.53). The development of any symptom was not statistically different between treatment groups (P = 0.12). There were 2 treatment-related deaths that occurred, 1 within each treatment group. ConclusionEndoluminal Gem/Doce and BCG have similar oncological outcomes and major adverse event rates in the treatment of UT-CIS. Further prospective evaluation is warranted.

Impact of a Special Operations Forces Basic Training on Body Composition and Energy Expenditure.

The Belgian Special Operations Regiment undergoes an 8-week basic training course (SOF Basic Course) following the Military Initiation Phase. The aims of the present study were to estimate energy expenditure and changes in body composition during SOF Basic Course. A multi frequency body composition analyser assessed baseline and endpoint body composition. For the purpose of estimating energy expenditure, 41 participants were fitted with triaxial accelerometers. T-tests were performed on paired and unpaired samples in order to estimate statistical significance. Effect size was estimated with Cohen's d. SOF Basic Course was completed by 88 out of 126 participants. The participants' mean (SD) age was 25.0 (4.1) years, weight was 77.6 (8.6) kg, and body fat percentage was 15.3% (3.3). Body weight of completers decreased from 78.3 (8.8) kg to 76.4 (8.0) kg (P = 0.01). Also, body fat decreased by 3.1 (1.8) kg (P = 0.01), and muscle mass increased by 1.2 (1.7) kg (P = 0.01). There was a decrease in body fat percentage from 15.3% (3.3) to 11.6% (3.4) (P = 0.01), with a Cohen's effect size of 1.86.The loss of 3.1 kg of body fat corresponds to a loss of 21,700.0 kcal (90.3 MJ) or 362.0 kcal.d-1 (1.5 MJ.d-1). The mean (SD) energy expenditure by physical activity was 1,943.0 (653.8) kcal.d-1 (14.6 [2.7] MJ.d-1). The average (SD) total energy expenditure was 4,088.0 (710.0) kcal.d-1 (36.8 [3.8] MJ.d-1). Tactical athletes must perform in hypo-energetic environment. Research in the future should investigate the impact of increased energy intake on body composition.

A Rare Case of Tuberculous Constrictive Pericarditis Due to Disseminated Tuberculosis with Response to Anti-tuberculosis Chemotherapy and Steroids in a Developed City State

A 27-year-old man presented with a 1-week history of atypical chest pain and sinus tachycardia. His physical examination was unremarkable. His resting ECG showed sinus tachycardia with widespread T-wave inversion. His initial blood tests show mildly raised troponin T and inflammatory markers and marked raised D-dimer. A CT pulmonary angiogram was performed to exclude pulmonary embolism but incidentally revealed an anterior mediastinal mass. A transthoracic echocardiogram and cardiac MRI showed features of constrictive pericarditis. A video-assisted thoracoscopic surgical biopsy of the anterior mediastinal mass showed thymic tissue with necrotising granulomatous inflammation and an acid-fast bacilli culture was positive to tuberculosis infection. The patient was started on anti-tuberculosis chemotherapy and a 6-week tapering course of oral steroids. A repeat cardiac MRI performed after 6 weeks of treatment showed a significant response to treatment with resolution of constrictive physiology.

Early Experience With Biologically Effective Dose-Comparable Short-Course Whole Brain Radiation Therapy for Metastatic Intracranial Disease.

For inpatients with metastatic intracranial disease burden exceeding established guidelines for stereotactic radiosurgery (SRS), the standard of care involves whole brain radiation therapy (WBRT), typically administered as a 2-week course of treatment with biologically effective dose (BED) of 60Gy. However, shorter course WBRT provides theoretical advantages in quality of life and decreasing systemic therapy delay. This retrospective study evaluates our early experience with BED-comparable short-course WBRT (23Gy in 5 fractions; BED=58.3Gy) for metastatic intracranial disease. Over a recent 2-month timeframe, 3 inpatients with intracranial disease burden exceeding SRS guidelines were administered BED-comparable short-course WBRT. Due to the high intracranial disease burden, 23Gy was chosen over 20Gy for 5-fraction WBRT due to the desire to optimally mimic the durability of the classic 30Gy in 10 fraction treatment regimen. The mean age at treatment was 65.7 years, the mean Karnofsky Performance Status (KPS) was 60, and the mean number of intracranial metastases was 20.3. The mean duration between inpatient Radiation Oncology consultation and the start of WBRT (following CT radiation therapy simulation) was 6.7 days. All patients completed WBRT no later than 2 weeks from the initial inpatient consultation. For inpatients with intracranial metastatic disease burden exceeding established SRS guidelines, BED-comparable short-course WBRT administered to 23Gy in 5 fractions (4.6Gy/fraction) is safe and efficacious. Given previous literature indicating that nearly half of the patients prescribed traditional 2-week WBRT die without completing treatment, BED-comparable WBRT represents an attractive and promising WBRT alternative in this patient population.

Emphasizing the Importance of Naproxen Prophylaxis May Decrease the Rate of Heterotopic Ossification After Hip Arthroscopy

To investigate the incidence of heterotopic ossification (HO) in patients prescribed prophylactic nonsteroidal anti-inflammatory drugs (NSAIDs), both before and after the introduction of a standardized education protocol. A retrospective review was conducted using a database of hip arthroscopy patients treated by a single surgeon at an academic hospital from 2015 to 2023. The inclusion criteria were (1) primary hip arthroscopy for the treatment of femoroacetabular impingement, (2) completion of a 2-week course of prophylactic postoperative NSAIDs (500 mg of naproxen twice daily), and (3) availability of follow-up radiographs at the 6-month postoperative visit. The control cohort was merely prescribed the postoperative prophylactic NSAIDs, whereas the intervention cohort also received dedicated in-person education, emphasizing the importance of NSAID adherence. The presence of HO was determined through review of follow-up radiographs. Standard descriptive statistics were used to describe the findings. Both the control and intervention groups consisted of 200 continuous hip arthroscopy patients, with the control group treated from 2015 to 2017 and the intervention group treated from 2020 to 2023. Within the control group, 10 cases of HO (5%) were detected. Within the intervention group, 2 cases of HO (1%) were found. The Pearson χ2 test with Yates continuity correction produced a value of 4.21, with a P value of .04. In this study, we found a significantly lower incidence rate of HO in patients who received standardized education on the importance of NSAID compliance versus those who did not. This finding suggests that patient education may play a contributory role in reducing the incidence of HO after hip arthroscopy. Level III, comparative cohort study.

The significance of subjective mechanical symptoms in rotator cuff pathology

BackgroundThe presence of subjective mechanical symptoms, such as clicking or popping, is common in patients presenting for shoulder pain and dysfunction, with unclear clinical significance. The primary objective of this study was to assess whether subjective mechanical symptoms in the affected shoulder were associated with full-thickness rotator cuff tearing in a consecutive, prospective cohort of patients undergoing shoulder magnetic resonance imaging (MRI) for suspected rotator cuff pathology. MethodsA prospective cohort study was performed of 100 consecutive patients with suspected rotator cuff tendinopathy and/or tearing who underwent shoulder MRI. The presence of subjective shoulder mechanical symptoms, including clicking or popping, was documented prior to MRI. Indications for MRI included weakness on isolated testing of rotator cuff muscle(s) or symptoms refractory to conservative treatment including at least a 6-week course of physical therapy. The primary outcome variable was the presence of full-thickness rotator cuff tearing; secondary outcome variables included any (full-thickness or partial-thickness) rotator cuff tearing and biceps long head subluxation. Radiographic parameters, including critical shoulder angle, Goutallier grade, tear retraction, and tear size were quantified. One patient was lost to follow-up, and 99 patients completed MRI imaging. ResultsIn our cohort, 60% of patients reported subjective mechanical symptoms in the affected shoulder. Full-thickness rotator cuff tearing was identified in 42% of patients, any rotator cuff tearing in 69% of patients, and biceps long head subluxation in 14% of patients. Subjective mechanical symptoms were not associated with full-thickness rotator cuff tearing, any rotator cuff tearing, biceps long head subluxation, critical shoulder angle, Goutallier grade, tear size, or tear retraction. Older age was associated with full-thickness and any rotator cuff tearing. As a diagnostic test for full-thickness rotator cuff tearing, subjective shoulder mechanical symptoms has a sensitivity of 64%, a specificity of 44%, and Youden’s index of 0.08, consistent with poor diagnostic accuracy. ConclusionsSubjective mechanical symptoms in the affected shoulder are a common complaint in patients with suspected rotator cuff pathology. Patients may be reassured that a sensation of clicking or popping alone does not necessarily entail structural shoulder derangement.

A Case of Deep Cutaneous Mycosis Caused by Purpureocillium lilacinum

Purpureocillium lilacinum, previously known as Paecilomyces lilacinus, is a saprophytic fungus typically found in soil and decaying vegetation. Although it is infrequently pathogenic to humans, recent reports of P. lilacinum infections, primarily affecting the skin and eyes, have shown an increase. This report details a cutaneous infection caused by P. lilacinum in an 89-year-old woman. She presented with a 3-month history of an erythematous patch and nodule on her right forearm. A skin biopsy revealed inflammation, granuloma, and fungal organisms in the dermis. Periodic acid-Schiff (PAS) staining confirmed the presence of fungal elements. The fungal culture of the medium produced colonies with a velvety pink and brown hue. PCR testing on these cultured samples identified P. lilacinum. The patient received a 2-week course of oral itraconazole (200 mg/day), which improved her symptoms. However, ongoing antifungal treatment was necessary. Additionally, due to a recent myocardiac infarction, the patient required a statin. A MIC test was conducted to identify an antifungal drug compatible with statin therapy.

The First Case of Phaeohyphomycosis Caused by Exophiala xenobiotica in an Immunocompetent Patient in Korea

Phaeohyphomycosis is a rare fungal infection caused by dematiaceous fungi commonly associated with immunocompromised patients. Exophiala (E.) species are linked to phaeohyphomycosis, and in Korea, E. dermatitidis, E. jeanselmei, and E. salmonis were previously isolated from affected patients. Here, we describe a unique instance of phaeohyphomycosis in an immunocompetent patient attributed to E. xenobiotica. A 75-year-old female presented with an asymptomatic erythematous crusted subcutaneous nodule on the dorsum of her left-hand. Her past medical history was negative for immunosuppression or trauma to the affected area. Histopathological examination revealed suppurative granulomatous infiltration, with septate hyphae and spores detected by periodic acid-Schiff staining in the dermis. A fungal culture made from a tissue sample revealed E. xenobiotica, with subsequent confirmation through phylogenetic analyses of the internal transcribed spacer (ITS) and large subunit regions (LSU) of ribosomal ribonucleic acid (rRNA). The patient was diagnosed with phaeohyphomycosis and underwent a 3-week course of terbinafine, followed by 7 weeks of fluconazole. These treatments significantly improved the lesion. To our knowledge, this is the first reported case of phaeohyphomycosis caused by E. xenobiotica in Korea.

Predictors of Tumor Dynamics Over a 6-Week Course of Concurrent Chemoradiotherapy for Glioblastoma and the Effect on Survival

We present the final analyses of tumor dynamics and their prognostic significance during a 6-week course of concurrent chemoradiotherapy for glioblastoma in the Glioblastoma Longitudinal Imaging Observational study. This is a prospective serial magnetic resonance imaging study in 129 patients with glioblastoma who had magnetic resonance imaging obtained at radiation therapy (RT) planning (F0), fraction 10 (F10), fraction 20 (F20), and 1-month post-RT. Tumor dynamics assessed included gross tumor volume relative to F0 (Vrel) and tumor migration distance (dmigration). Covariables evaluated included: corpus callosum involvement, extent of surgery, O6-methylguanine-DNA-methyltransferase methylation, and isocitrate dehydrogenase mutation status. The median Vrel were 0.85 (range, 0.25-2.29) at F10, 0.79 (range, 0.09-2.22) at F20, and 0.78 (range, 0.13-4.27) at 1 month after completion of RT. The median dmigration were 4.7 mm (range, 1.1-20.4 mm) at F10, 4.7 mm (range, 0.8-20.7 mm) at F20, and 6.1 mm (range, 0.0-45.5 mm) at 1 month after completion of RT. Compared with patients who had corpus callosum involvement (n = 26), those without corpus callosum involvement (n = 103) had significant Vrel reduction at F20 (P = .03) and smaller dmigration at F20 (P = .007). Compared with patients who had biopsy alone (n = 19) and subtotal resection (n = 71), those who had gross total resection (n = 38) had significant Vrel reduction at F10 (P = .001) and F20 (P = .001) and a smaller dmigration at F10 (P = .03) and F20 (P = .002). O6-Methylguanine-DNA-methyltransferase methylation and isocitrate dehydrogenase mutation status were not significantly associated with tumor dynamics. The median progression-free survival and overall survival (OS) were 8.5 months (95% CI, 6.9-9.9) and 20.4 months (95% CI, 17.6-25.2). In multivariable analyses, patients with Vrel ≥ 1.33 at F10 had worse OS (hazard ratio [HR], 4.6; 95% CI, 1.8-11.4; P = .001), and patients with dmigration ≥ 5 mm at 1-month post-RT had worse progression-free survival (HR, 1.76; 95% CI, 1.08-2.87) and OS (HR, 2.2; 95% CI, 1.2-4.0; P = .007). Corpus callosum involvement and extent of surgery are independent predictors of tumor dynamics during RT and can enable patient selection for adaptive RT strategies. Significant tumor enlargement at F10 and tumor migration 1-month post-RT were associated with poorer OS.

Cumulative Blast Impulse Is Predictive for Changes in Chronic Neurobehavioral Symptoms Following Low Level Blast Exposure during Military Training.

Cumulative low-level blast exposure during military training may be a significant occupational hazard, increasing the risk of poor long-term outcomes in brain function. US Public Law 116-92 section717 mandates that US Department of Defense agencies document the blast exposure of each Service member to help inform later disability and health care decisions. However, which empirical measures of training blast exposure, such as the number of incidents, peak overpressure, or impulse, best inform changes in the neurobehavioral symptoms reflecting brain health have not been established. This study was approved by the US Army Special Operations Command, the University of North Carolina at Chapel Hill, and the VA Puget Sound Health Care System. Using methods easily deployable across different organizational structures, this study sought to identify and measure candidate risk factors related to career occupational blast exposure predictive of changes in neurobehavioral symptom burden. Blast dosimetry-symptom relationships were first evaluated in mice and then tested in a military training environment. In mice, the righting time neurobehavioral response was measured after exposure to a repetitive low-level blast paradigm modeled after Special Operations training. In the military training environment, 23 trainees enrolled in a 6-week explosive breaching training course, 13 instructors, and 10 Service member controls without blast exposure participated in the study (46 total). All participants provided weekly Neurobehavioral Symptom Inventory (NSI) surveys. Peak blast overpressure, impulse, total number of blasts, Time in Low-Level Blast Occupation, and Time in Service were analyzed by Bayesian analysis of regression modeling to determine their probability of influence on the post-training symptoms reported by participants. We tested the hypothesis that cumulative measures of low-level blast exposure were predictive of changes in neurobehavioral symptoms. In mice, repetitive blast resulted in reduced righting times correlated with cumulative blast impulse. In Service members, peak blast overpressure, impulse, total number of blasts, Time in Low-Level Blast Occupation, and Time in Service all showed strong evidence of influence on NSI scores after blast exposure. However, only models including baseline NSI scores and cumulative blast impulse provided significant predictive value following validation. These results indicate that measures of cumulative blast impulse may have utility in predicting changes in NSI scores. Such paired dosimetry-symptom measures are expected to be an important tool in safely guiding Service members' occupational exposure and optimizing force readiness and lethality.