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Background: The primary aim of this study was to demonstrate the benefits of topical human platelet exosome extract (HPE) (plated) hair serum for improving hair and scalp health in participants with self-perceived thinning hair. Methods: This single-center, placebo-controlled, double-blind study enrolled 39 healthy men and women 18–65 years of age with self-perceived thinning hair. Participants applied either HPE for 9 months or a topical placebo for 6 months with the option to cross over to HPE at 6 months for an additional 3 months. End points included improvements in the global aesthetic appearance of hair, as assessed by a blinded live evaluator; participant-reported outcomes; hair trichoscopy; and independent physician photograph evaluations. Safety data included monitoring for adverse events. Results: Blinded live evaluator assessments demonstrated statistically significant improvements in the global aesthetic appearance of hair for volume/fullness, density, scalp coverage, and appearance, with all P values less than 0.0001 within the HPE group and statistical improvement over the control at months 3 and 6 for volume/fullness, density, and scalp coverage. Participant-reported outcomes for within-group changes for HPE were statistically significant for all hair health parameters, including density, volume fullness, scalp coverage, scalp health, thickness, amount, quality, color, dryness, strength, and overall health of the hair. Hair trichoscopy analyses were significantly improved from baseline within the HPE group. Independent physician photography review demonstrated greater improvements within the HPE group. No adverse effects were observed. Conclusions: This study demonstrates that topical HPE (plated) hair serum with Renewosome technology significantly improves hair and scalp health and is safe and well tolerated.

ABSTRACTBackgroundDespite the general perception of minimal donor‐site morbidity associated with scapular free flaps, the surgical harvest of scapular bone and subsequent reattachment of parascapular muscle have the potential to compromise postoperative shoulder function. A comprehensive assessment of functional impairment remains undocumented in the literature. Therefore, this systematic review was conducted to thoroughly explore both subjective and objective donor‐site morbidity following free flap surgery.MethodsSearches were conducted on PubMed, Embase, and CENTRAL to locate articles addressing functional donor‐site morbidity after the transfer of scapular bone. Qualifying articles reported scapular free flaps which utilized bone, including lateral border, medial border, and scapular tip. Each measured donor‐site morbidity using at least one of these measures: Constant‐Murley score (CM), Disabilities of Arm, Shoulder, and Hand questionnaire (DASH), shoulder range of motion (ROM), and shoulder strength.ResultsThe search culminated in 16 eligible studies, incorporating data from 316 cases. The CM was employed in five studies, yielding mean values from 60.6 to 95, while the DASH was utilized in nine studies, with means ranging from 10.44 to 46.7. Compared to normative values, these CM and DASH scores reflected negligible to mild impairment in shoulder function. Additional evaluations of shoulder ROM, conducted in four studies, revealed modest yet statistically significant reductions in flexion, abduction, and external rotation. Three studies measuring shoulder strength reported associated mild weakening of these motions.ConclusionsThis systematic review enables healthcare providers to characterize the probable scope of shoulder dysfunction following scapular bone harvest. Patient‐reported outcomes imply a high tolerance for the procedure, while objective measures denote the potential for substantial restoration of shoulder function approaching preoperative levels. To augment the understanding of functional recovery, future research should incorporate a comparative analysis of preoperative and postoperative functional metrics for each subject.

Abstract Background Projectile and target fragmentation are nuclear phenomena that can influence the computation of the linear energy transfer (LET) and the relative biological effectiveness (RBE) in external radiotherapy with accelerated ions. Correlations between these two quantities are routinely established during radiobiological experiments to interpret the results and to develop and calibrate RBE models. Purpose This study systematically evaluates the impact of secondary fragments and irradiation scenarios on the dose‐averaged LET, the RBE, and their correlation in the case of exposures to clinically relevant ion beams. Methods 57 600 microdosimetric lineal energy spectra and corresponding LET distributions were simulated with the Monte Carlo code PHITS across different scenarios, including track segment calculations, pristine, and spread‐out Bragg peaks of 1 H, 4 He, 12 C, 16 O, and 20 Ne ions within water phantoms. The LET distributions were analyzed to calculate the dose‐average LET, both including or excluding the contribution of secondary ions of an element different from the primary beam. Similarly, the lineal energy distributions were processed in conjunction with the Mayo Clinic Florida microdosimetric kinetic model to compute the RBE for two theoretical cell lines ( α / β = 2 and 10 Gy in the case of 6 MV x‐rays). Correlations between the RBE and dose‐averaged LET were established by analyzing the simulation results within water phantoms and then compared to the corresponding trends from the track segment calculations. Results Excluding secondary fragments had a pronounced impact on the dose‐averaged LET and the RBE, particularly in the entrance regions of proton beams and close to the distal edge of heavier ions. The correlations between the RBE and the dose‐averaged LET were not universal, but highly dependent on the irradiation scenario. For proton beams only, the dose‐averaged LET of hydrogen ions served as a practical first‐order descriptor of the RBE. Track segment simulations, commonly used for calibrating and benchmarking RBE models, provided a reasonable approximation for low‐energy beams but failed to fully capture the complexity of polyenergetic radiation fields. Conclusions Secondary fragments can substantially affect the dose‐averaged LET and the RBE, even in proton beams. The dose‐averaged LET, including or not the contributions from secondary fragments, was generally unable to adequately capture RBE variations across different scenarios. A more comprehensive approach, considering microdosimetric distributions, is necessary to accurately describe RBE variations in ion therapy.

ABSTRACTBackground and AimsLeucine Zipper 4 (LUZP4)‐immunoglobulin G (IgG) is a novel antibody implicated in germ cell tumor‐related paraneoplastic neurologic syndrome. We report a case of painful, progressive tetraparesis associated with testicular seminoma and LUZP4‐IgG seropositivity.Case ReportA 51‐year‐old male presented with a 5‐week history of lower limb predominant progressive weakness. Nerve conduction studies (NCS) and electromyography (EMG) revealed a subacute axonal polyradiculoneuropathy. MRI lumbar spine showed thickening of the cauda equina and enhancement of the lower thoracic spinal cord/conus. Cerebrospinal fluid (CSF) showed a lymphocytic pleocytosis, three oligoclonal bands, and mildly elevated protein. Initial treatment with intravenous immunoglobulin (IVIG) and prednisone produced temporary improvement. CT targeted retroperitoneal lymph node biopsy revealed a seminoma, which was treated with orchiectomy and chemotherapy. The testicular tissue was consistent with a regressed germ cell tumor. His course was subsequently refractory to IVIG, prednisone, and plasma exchange. LUZP4 antibodies were detected in serum, prompting treatment with cyclophosphamide and prednisone. At the 4‐month follow‐up, the patient had significant improvement in hand strength and had transitioned from walker to cane.InterpretationLUZP4‐IgG seropositivity and identification of retroperitoneal seminoma confirmed a paraneoplastic neurologic syndrome, which is a CD8+ T‐cell‐mediated disorder. Aggressive immunotherapy was initiated, resulting in clinical improvement. This case underscores the importance of identifying specific serologic biomarkers that can inform therapeutic decisions and improve outcomes.

Abstract Purpose: The aim of PREDICT was to confirm clinical validity and the potential for clinical utility of serial circulating tumor cell (CTC) enumeration in patients with metastatic breast cancer, focusing on its prognostic value in different breast cancer subtypes and clinical settings. Experimental Design: In total, 4,436 individual patient-level data with CTC results from both baseline and one follow-up (CellSearch; Menarini Silicon Biosystems) were analyzed to evaluate the association between CTC detection and overall survival (OS) in the full patient cohort and separately for tumor and treatment types. Results: Using the cutoff ≥1 CTC for CTC positivity, 913 (20.6%) patients had 0 CTCs at both time points (neg/neg) and 325 (7.3%) and 1,189 (26.8%) patients converted from CTC negative to CTC positive (neg/pos) or vice versa (pos/neg), whereas 2,009 (45.3%) patients had at least one CTC at both time points (pos/pos). The median OS for the neg/neg, neg/pos, pos/neg, and pos/pos group was 45.6, 26.1, 32.3, and 17.3 months, respectively (P < 0.0001, global log-rank test). CTC responders (pos/neg) showed a lower risk of death compared with CTC nonresponders (pos/pos; HR, 0.48; 95% confidence interval, 0.44–0.53). Similar results were obtained in subgroup analyses according to hormone receptor and HER2 subtype, treatment type, and with a ≥5 CTC cutoff for CTC positivity. Conclusions: Follow-up CTC assessments strongly predict OS independently from tumor subtype and treatment. New randomized trials to define the clinical utility of CTC monitoring for risk stratification and as an early response marker in metastatic breast cancer are urgently needed.

In this review, we discuss the risks and adverse effects reported for the current Food and Drug Association (FDA)-approved biologics used in the management of asthma, including omalizumab, benralizumab, dupilumab, mepolizumab, reslizumab, and tezepelumab. Our review focuses on the risk of hypersensitivity reactions, infection, and malignancy. Where relevant, we have included information regarding the risk of cardiovascular disease and eosinophilia, and we have included specific information regarding vaccine use among patients receiving the above biologics. We also review currently available data regarding the use of biologics in the context of pregnancy. Our goal is to provide a comprehensive resource for providers utilizing these agents, so that they may adequately counsel patients about the risks of therapy and identify adverse events if they occur.

INTRODUCTION: Evidence-based recommendations for sexual practices regarding anoreceptive intercourse (ARI) do not exist in patients with inflammatory bowel diseases undergoing restorative proctocolectomy with ileal pouch anal anastomosis (IPAA). This study surveys providers on perspectives and attitudes related to sexual practices after IPAA. METHODS: We developed a 23-item survey and distributed it to providers caring for patients with inflammatory bowel diseases. RESULTS: 95% of providers believe that it is important to discuss sexual orientation or practices before IPAA, but only 27% routinely discuss this. 50% did not feel comfortable and 74% did not feel confident discussing ARI recommendations with patients who underwent or will undergo IPAA. DISCUSSION: Future interventions should aim to standardize recommendations regarding feasibility and time line to safe ARI after IPAA.

INTRODUCTION: Immune-modifying therapies in pediatric inflammatory bowel disease (IBD) increase infection risks, including varicella. METHODS: Using Optum's deidentified Clinformatics Data Mart Database, a nationwide US commercial insurance claims database (2007–2022), we conducted a retrospective study of 5,368 patients with IBD aged 21 years or younger matched to a non-IBD cohort. The primary outcome was incidence of varicella. RESULTS: Varicella incidence was low in both groups (IBD: 0.570 vs non-IBD: 0.297 per 1,000 person-years, P = 0.23). At year 4, cumulative varicella incidence was 0.27% for IBD and 0.18% for non-IBD ( P = 0.24). No hospitalizations or deaths occurred. DISCUSSION: Despite immune-modifying therapy, pediatric patients with IBD demonstrate low varicella incidence.

Music is one nonpharmacological intervention to reduce anxiety and stress for mechanically ventilated patients. Efficient delivery of a music listening intervention can be enhanced through digital tools such as a mobile application (app) loaded onto an electronic tablet device. The objective of this study is to describe the iterative development and deployment of a novel app (Soundese) to deliver, record, and retrieve data associated with a two-arm randomized, blinded clinical trial testing music listening intervention compared to control silence condition on delirium severity among critically ill intensive care unit (ICU) older adult patients receiving mechanical ventilatory support. The Soundese mobile app was developed to deliver either experimental music listening intervention or a silence control listening condition to a sample of older adults receiving mechanical ventilatory support in the ICU and retrieve all protocol data. The Soundese app was developed using the Swift software language and is compatible with all iOS devices. The Soundese app consists of two components: (1) a mobile app that delivers the assigned, blinded listening intervention from an iPad through headphones to each subject and automatically logs each listening session, its duration, the randomization arm, and uploads these data to a server, and (2) an analysis app that generates a spreadsheet with summarized data of the respective listening session, music details, and reports for further analyses. A Dropbox application programmer interface enabled the secure storage of files on a designated Dropbox account. After initial field testing and iterative development changes based on research staff feedback, the Soundese app delivers the assigned experimental listening condition or silence control condition when deployed remotely in the field. The app’s mobile nature allows for immediate and automatic data capture, which is summarized for statistical analysis. There is no need for any manual recording of any intervention data by busy ICU staff, including listening time or music selections. The Soundese mobile app efficiently delivers the research protocol with fidelity and collects the necessary data for an ICU-based clinical trial. The app may be useful in other clinical trials testing music listening interventions in various settings or for deploying other audio-based interventions.

Abstract Human immune system (HIS) mice constructed in various ways are widely used for investigations of human immune responses to pathogens, transplants and immunotherapies. In HIS mice that generate T cells de novo from hematopoietic progenitors, T cell-dependent multisystem autoimmune disease occurs, most rapidly when the human T cells develop in the native NOD.Cg- Prkdcscid Il2rgtm1Wjl (NSG) mouse thymus, where negative selection is abnormal. Disease develops very late when human T cells develop in human fetal thymus grafts, where robust negative selection is observed. We demonstrate here that PD-1+CD4+ peripheral (Tph) helper-like and follicular (Tfh) helper-like T cells developing in HIS mice can induce autoimmune disease. Tfh- like cells were more prominent in HIS mice with a mouse thymus, in which the highest levels of IgG were detected in plasma, compared to those with a human thymus. While circulating IgG and IgM antibodies were autoreactive to multiple mouse antigens, in vivo depletion of B cells and antibodies did not delay the development of autoimmune disease. Conversely, adoptive transfer of enriched Tfh- or Tph-like cells induced disease and autoimmunity-associated B cell phenotypes in recipient mice containing autologous human APCs without T cells. Tfh/Tph cells from mice with a human thymus expanded and induced disease more rapidly than those originating in a murine thymus, implicating HLA-restricted T cell-APC interactions in this process. Since Tfh, Tph, autoantibodies and lymphopenia-induced proliferation (LIP) have all been implicated in various forms of human autoimmune disease, the observations here provide a platform for the further dissection of human autoimmune disease mechanisms and therapies.