Search

Abstract Background Skeletal metastases present a major challenge for clinicians, representing an advanced and typically incurable stage of cancer. Bone is also the most common location for metastatic breast carcinoma, with skeletal lesions identified in over 80% of patients with advanced breast cancer. Preclinical models have demonstrated the ability of mechanical stimulation to suppress tumour formation and promote skeletal preservation at bone sites with osteolytic lesions, generating modulatory interference of tumour-driven bone remodelling. Preclinical studies have also demonstrated anti-cancer effects through exercise by minimising tumour hypoxia, normalising tumour vasculature and increasing tumoural blood perfusion. This study proposes to explore the promising role of targeted exercise to suppress tumour growth while concomitantly delivering broader health benefits in patients with advanced breast cancer with osteolytic bone metastases. Methods This single-blinded, two-armed, randomised and controlled pilot study aims to establish the safety, feasibility and efficacy of an individually tailored, modular multi-modal exercise programme incorporating spinal isometric training (targeted muscle contraction) in 40 women with advanced breast cancer and stable osteolytic spinal metastases. Participants will be randomly assigned to exercise or usual medical care. The intervention arm will receive a 3-month clinically supervised exercise programme, which if proven to be safe and efficacious will be offered to the control-arm patients following study completion. Primary endpoints (programme feasibility, safety, tolerance and adherence) and secondary endpoints (tumour morphology, serum tumour biomarkers, bone metabolism, inflammation, anthropometry, body composition, bone pain, physical function and patient-reported outcomes) will be measured at baseline and following the intervention. Discussion Exercise medicine may positively alter tumour biology through numerous mechanical and non-mechanical mechanisms. This randomised controlled pilot trial will explore the preliminary effects of targeted exercise on tumour morphology and circulating metastatic tumour biomarkers using an osteolytic skeletal metastases model in patients with breast cancer. The study is principally aimed at establishing feasibility and safety. If proven to be safe and feasible, results from this study could have important implications for the delivery of this exercise programme to patients with advanced cancer and sclerotic skeletal metastases or with skeletal lesions present in haematological cancers (such as osteolytic lesions in multiple myeloma), for which future research is recommended. Trial registration anzctr.org.au, ACTRN-12616001368426. Registered on 4 October 2016.

A cluster of sporotrichosis cases occurred in the Busselton-Margaret River region of Western Australia from 2000 to 2003. Epidemiologic investigation and mycologic culture for Sporothrix schenckii implicated hay initially distributed through a commercial hay supplier as the source of the outbreak. Declining infection rates have occurred after various community measures were instigated.

Introduction: Axillary response to neoadjuvant endocrine therapy (NET) for the treatment of hormone receptor-positive breast cancer (HR+ BC) is not well-described. This study was designed to characterize nodal response after NET., Methods: Patients receiving NET followed by curative intent surgery at a comprehensive cancer center from 1998 to 2022 in a prospectively collected registry were included. Patients with distant metastasis were excluded. Primary outcome was nodal pathologic complete response (pCR). Downstaging was defined as post-NET decrease in category., Results: We included 123 patients; the majority were cT2 (n = 59) or cT3 (n = 35), and cN0 (n = 81). Median age was 70.0 years (interquartile range 62.1-76.0). Forty-two patients (34.1%) were clinically node-positive. After NET, 73 (59.8%) underwent breast-conserving surgery. All patients underwent sentinel lymph node biopsy, and 12 (9.8%) underwent completion axillary lymph node dissection. In-breast downstaging was achieved in 51 (41.5%) patients, 1 (0.8%) had breast pCR, and 14 (11.4%) had breast upstaging. Axillary downstaging was achieved in 10 (23.8%), 6 patients (14.3%) had nodal pCR, and 14 (33.3%) had axillary upstaging. At 10-year follow-up, local recurrence was 1% and distant recurrence was 14%, while disease-free survival was 82%. After adjusting for demographic and clinical factors, age was the only characteristic associated with mortality (hazard ratio 1.07, 95% confidence interval 1.01-1.13)., Conclusions: In HR+ BC treated with NET, long-term disease-free survival is good, although nodal pCR is uncommon for cN+ patients. Future studies are needed to elucidate optimal neoadjuvant systemic therapy and to delineate oncologically safe strategies to deescalate axillary management for residual microscopic disease., (© 2024. Society of Surgical Oncology.)

Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the UK Medical Research Council, Norwegian Research Council, NIH/NHLBI, Measey Foundation, and Doris Duke Foundation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work; TF has received funding from Pfizer, Takeda, Acadia, and iHeed for unrelated consulting work, and receives funds from The BMJ for editorial work; NMD receives funds from The BMJ for editorial work; SMD receives research support from RenalytixAI and Novo Nordisk, outside the scope of the current research.

Background: The role of immune-oncology (IO) therapy in soft tissue sarcoma (STS) is underexplored. This study characterized IO use in STS., Methods: This is a retrospective analysis of patients with a soft tissue mass in the National Cancer Database, 2011-2021. Patients were categorized by IO receipt status. Groupwise testing and proportional trend tests were performed with Chi-squared tests. Multivariate logistic regression was performed to assess factors associated with IO receipt., Results: Of the 103,092 patients with STS, 1935 (1.9 ​%) received or were recommended IO therapy. IO use increased 10-fold (0.24 ​%-2.5 ​% from 2011 to 2021; p ​< ​0.0001). Patients had higher odds of receiving IO when having higher grade tumors and metastatic disease, and when treated at an academic research center (all p ​< ​0.001)., Conclusions: IO use in STS is low but increasing and primarily used in the metastatic setting. Future studies should identify biomarkers of IO response and facilitators for treatment receipt., Competing Interests: Declaration of competing interest None of the authors have any relevant conflicts of interest to disclose. TKY reports grants from the Radiation Oncology Institute and Lineberger Comprehensive Cancer Center., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency., Methods: We retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m 2 and cyclophosphamide 500 mg/m 2 for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m 2 and cyclophosphamide 500 mg/m 2 for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity., Results: From June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin's lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2-4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2-4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026)., Discussion: As the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Frame, Geer, Kasha, Markstrom, Scappaticci, Feeney, Hayduk, Mansoor, Oberfeld, D’Antonio, Anand, Choi, Maciejewski, Pawarode, Riwes, Tewari, Magenau and Ghosh.)

The long-term stability of perovskite solar cells (PSCs) remains a bottleneck for commercialization. While studies on the stoichiometry and morphology of PSCs with regard to performance are prevalent, understanding the influence of these factors on their long-term stability is lacking. In this work, we evaluate the impact of stoichiometry and morphology on the long-term stability of cesium formamidinium-based PSCs. We demonstrate that the lead iodide (PbI 2 ) to formamidinium iodide (FAI) ratio influences stability under various stress factors (elevated temperature and light). A high molar ratio (PbI 2 /FAI > 1.1) in the perovskite precursor displays drastic degradation under ISOS-L1 (100 mW/cm 2 , 25 °C, maximum power point tracking) conditions. However, postdegradation analysis contradicts these results. Devices with PbI 2 /FAI ≤ 1.1 are stable under light, but intermittent current density-voltage characterizations indicate that device performance decreases during storage in the dark. Migration of iodide (I - ) ions to the electron-transport layer (ETL) and iodine vacancies (V I- + ) to the hole-transport layer (HTL) forms localized shunts in the absorber layer. Pinhole formation, surrounded by FA + -rich regions, explains the extent of damage in comparably aged films. In summary, this work emphasizes the importance of reporting stability under different stress conditions, coupled with postdegradation and dark recovery analyses of PSCs to better understand the complexities of perovskite instability under real-life conditions such as expected during outdoor operation.

Background: Appropriate follow-up of incidental adrenal masses (IAMs) is infrequent. We implemented a quality improvement (QI) program to improve management of IAMs., Study Design: This system-wide initiative targeted primary care providers (PCPs) after IAM detection. It incorporated (1) chart-based messages and emails to PCPs, (2) an evidence-based IAM evaluation algorithm, (3) standardized recommendations in radiology reports, and (4) access to a multispecialty adrenal clinic. Patients diagnosed with an IAM from January 1, 2018, to December 31, 2019, were prospectively included (the "QI cohort") and compared with a historical, preintervention cohort diagnosed with IAMs in 2016. The primary outcomes were the initiation of an IAM investigation by the PCP, defined as relevant clinical history-taking, laboratory screening, follow-up imaging, or specialist referral., Results: The QI cohort included 437 patients and 210 in the historical cohort. All patients had 12 months or more of follow-up. In the QI cohort, 35.5% (155 of 437) met the primary endpoint for PCP-initiated evaluation, compared with 27.6% (58 of 210) in the historical cohort (p = 0.0496). Among the subgroup with a documented PCP working within our health system, 46.3% (74 of 160) met the primary endpoint in the QI cohort vs 33.3% (38 of 114) in the historical cohort (p = 0.035). After adjusting for insurance status, presence of current malignancy, initial imaging setting (outpatient, inpatient, or emergency department), and having an established PCP within our health system, patients in the QI cohort had 1.70 times higher odds (95% CI 1.16 to 2.50) of undergoing a PCP-initiated IAM evaluation. Adrenal surgery was ultimately performed in 2.1% (9 of 437) of QI cohort patients and 0.95% (2 of 210) of historical cohort patients (p = 0.517)., Conclusions: This simple, moderately labor-intensive QI intervention was associated with increased IAM evaluation initiated by PCPs., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

The recent tremendous progress in monolithic perovskite-based double-junction solar cells is just the start of a new era of ultra-high-efficiency multi-junction photovoltaics. We report on triple-junction perovskite-perovskite-silicon solar cells with a record power conversion efficiency of 24.4%. Optimizing the light management of each perovskite sub-cell (∼1.84 and ∼1.52 eV for top and middle cells, respectively), we maximize the current generation up to 11.6 mA cm -2 . Key to this achievement was our development of a high-performance middle perovskite sub-cell, employing a stable pure-α-phase high-quality formamidinium lead iodide perovskite thin film (free of wrinkles, cracks, and pinholes). This enables a high open-circuit voltage of 2.84 V in a triple junction. Non-encapsulated triple-junction devices retain up to 96.6% of their initial efficiency if stored in the dark at 85 °C for 1081 h., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Endothelial cell activation and injury is common after hematopoietic stem cell transplant (HSCT) and is associated with many post-transplant complications. An underexplored mechanism of endothelial cell damage in this population is the infusion of normal saline (NS, 0.9 % sodium chloride) and other crystalloids, as NS use is associated with adverse outcomes in other patient populations. We hypothesized that the infusion of unbalanced crystalloids during HSCT may lead to changes in biomarkers commonly associated with red blood cell (RBC) hemolysis in patients before and after infusion, and that markers of endothelial and end-organ damage during admission may be associated with markers of hemolysis and total crystalloid use. Samples were collected from 97 patients. From pre-fluid infusion to post-fluid infusion, mean haptoglobin decreased (11.7 ug/ml vs 8.4 ug/ml; p < 0.0001), hemopexin decreased (549 vs 512 μg/ml; p = 0.005), and red cell distribution width (RDW) decreased (15.7 vs 15.6; p = 0.0009). During admission (mean 19.4 days, SD 9.9), all markers of tissue and organ damage, including mean creatinine, lactate dehydrogenase (LDH), blood urea nitrogen (BUN), total bilirubin, AST, and ALT, increased from admission to peak levels (p < 0.0001). On linear regression, fluid volume (ml/kg) of crystalloid infusion positively predicted post-fluid infusion cell-free hemoglobin (r(96) = 0.34, p < 0.0001), free heme (r(96) = 0.36, p < 0.0001), and peak LDH during admission (r(75) = 0.23, p = 0.041), and negatively predicted post-fluid infusion hemopexin (r(96) = - 0.34, p < 0.0001). Unbalanced crystalloids may contribute to hemolysis and endothelial damage in HSCT patients. Alternatives such as buffered crystalloid solutions (PlasmaLyte, Lactated Ringer's) may be worth investigating in this population., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Post transition metal chalcohalides are an emerging class of semiconductor materials for optoelectronic applications. Within this class, bismuth oxyiodide (BiOI) is of particular interest due to its high environmental stability, low toxicity, and defect tolerance considered typical of 'ns 2 ' materials. Here we fabricate BiOI thin films using a solution-processed method that affords pin-hole free highly pure films without any residual carbon or other contaminant species. Based on these films, solution processed all-inorganic solar cells with an architecture ITO/NiO x /BiOI/ZnO/Al are fabricated for the first time. Additional device improvements are realised by templating BiOI thin film growth to attain efficiencies that rival some of the best vacuum deposited devices. The BiOI thin films and devices outlined here are an excellent platform for the further development of solution processed bismuth chalcohalide optoelectronic devices., (Creative Commons Attribution license.)

Perovskite gain materials can sustain continuous-wave lasing at room-temperature. A first step toward the unachieved goal of electrically excited lasing would be an improvement in gain when electrical stimulation is added to the optical. However, to date, electrical stimulation supplementing optical has reduced gain performance. We find that amplified spontaneous emission (ASE) in a CsPbBr 3 perovskite light-emitting diode (LED) held under invariant subthreshold optical excitation can be turned on/off by the addition/removal of an electric field. A positive bias voltage leads to a factor of 3 reduction in the optical ASE threshold, the cause of which can be attributed to an enhancement of the radiative rate. The slow components (10 s time scale) of the modulation in the photoluminescence and ASE when the voltage is changed suggest that the relocation of mobile ions trigger the increased radiative rate and observed lowering of ASE thresholds.

Purpose: Incidental adrenal masses (IAMs) are common but rarely evaluated. To improve this, we developed a standardized radiology report recommendation template and investigated its implementation and effectiveness., Methods: We prospectively studied implementation of a standardized IAM reporting template as part of an ongoing quality improvement initiative, which also included primary care provider (PCP) notifications and a straightforward clinical algorithm. Data were obtained via medical record review and a survey of radiologists. Outcomes included template adoption rates and acceptability (implementation measures), as well as the proportion of patients evaluated and time to follow-up (effectiveness outcomes)., Results: Of 4,995 imaging studies, 200 (4.0%) detected a new IAM. The standardized template was used in 54 reports (27.0%). All radiologists surveyed were aware of the template, and 91% affirmed that standardized recommendations are useful. Patients whose reports included the template were more likely to have PCP follow-up after IAM discovery compared with those with no template (53.7% versus 36.3%, P = .03). After adjusting for sex, current or prior malignancy, and provider ordering the initial imaging (PCP, other outpatient provider, or emergency department or inpatient provider), odds of PCP follow-up remained 2.0 times higher (95% confidence interval 1.02-3.9). Patients whose reports included the template had a shorter time to PCP follow-up (log-rank P = .018). PCPs ultimately placed orders for biochemical testing (35.2% versus 18.5%, P = .01), follow-up imaging (40.7% versus 23.3%, P = .02), and specialist referral (22.2% versus 4.8%, P < .01) for a higher proportion of patients who received the template compared with those who did not., Conclusions: Use of a standardized template to communicate IAM recommendations was associated with improved IAM evaluation. Our template demonstrated high acceptability, but additional strategies are necessary to optimize adoption., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Objectives: Generating and using real-world evidence (RWE) is a pragmatic solution for evaluating health technologies. RWE is recognized by regulators, health technology assessors, clinicians, and manufacturers as a valid source of information to support their decision-making. Well-designed registries can provide RWE and become more powerful when linked with electronic health records and administrative databases in coordinated registry networks (CRNs). Our objective was to create a framework of maturity of CRNs and registries, so guiding their development and the prioritization of funding., Design Setting and Participants: We invited 52 stakeholders from diverse backgrounds including patient advocacy groups, academic, clinical, industry and regulatory experts to participate on a Delphi survey. Of those invited, 42 participated in the survey to provide feedback on the maturity framework for CRNs and registries. An expert panel reviewed the responses to refine the framework until the target consensus of 80% was reached. Two rounds of the Delphi were distributed via Qualtrics online platform from July to August 2020 and from October to November 2020., Main Outcome Measures: Consensus on the maturity framework for CRNs and registries consisted of seven domains (unique device identification, efficient data collection, data quality, product life cycle approach, governance and sustainability, quality improvement, and patient-reported outcomes), each presented with five levels of maturity., Results: Of 52 invited experts, 41 (79.9%) responded to round 1; all 41 responded to round 2; and consensus was reached for most domains. The expert panel resolved the disagreements and final consensus estimates ranged from 80.5% to 92.7% for seven domains., Conclusions: We have developed a robust framework to assess the maturity of any CRN (or registry) to provide reliable RWE. This framework will promote harmonization of approaches to RWE generation across different disciplines and health systems. The domains and their levels may evolve over time as new solutions become available., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Several studies demonstrated language that discordant care between may lead to mixed outcomes and increased use of hospital-resources. In the setting of bariatric surgery, which relies heavily on intensive pre-operative and post-operative counseling, we hypothesized that patients with LEP would have less favorable outcomes compared to English-proficient (EP) patients., Methods: All patients 18 years and older, who underwent laparoscopic sleeve gastrectomy (SG) or laparoscopic gastric bypass (LGBP) from January 2013 to December 2017 were included. Language proficiency was determined by chart review for the use of an interpreter at least once during the study period. Outcomes of interest at 30-days and 1 year included: emergency department (ED) visits, readmission, length of stay (LOS), chief-complaint on readmission, and post-operative complications. Additionally, comorbidity remission and weight loss at one year was recorded., Results: A total of 671 patients were categorized as LEP (40%) and spoke 6 unique languages. Within the 1 year post-operative period, EP patients presented to the ED more than LEP patients (23% vs. 14% p &lt; 0.001). After multivariable regression for potential confounders this difference persisted; adjusted OR = 0.65 (95% CI 0.43-0.95; p = 0.029). However, despite more frequent ED visits by EP patients, there was no significant difference in readmission within one year; adjusted OR = 0.94 (95% CI 0.56-1.55; p = 0.50). Both groups demonstrated similar successful weight loss at 1 year: EP-31.85% (LGBP) and - 28.02% (SG) vs. LEP-30.17% (LGBP) and - 28.36% (SG). EP and LEP patients also had similar remission of obesity-related comorbidities., Conclusion: There were no differences in outcomes following bariatric surgery when comparing patients with limited English proficiency to those who are proficient in English. Bariatric surgical care can be delivered in a safe and effective manner with equivalent outcomes between patients who are and are not English-language proficient., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Monolithic two-terminal (2T) perovskite/CuInSe 2 (CIS) tandem solar cells (TSCs) combine the promise of an efficient tandem photovoltaic (PV) technology with the simplicity of an all-thin-film device architecture that is compatible with flexible and lightweight PV. In this work, we present the first-ever 2T perovskite/CIS TSC with a power conversion efficiency (PCE) approaching 25% (23.5% certified, area 0.5 cm 2 ). The relatively planar surface profile and narrow band gap (∼1.03 eV) of our CIS bottom cell allow us to exploit the optoelectronic properties and photostability of a low-Br-containing perovskite top cell as revealed by advanced characterization techniques. Current matching was attained by proper tuning of the thickness and bandgap of the perovskite, along with the optimization of an antireflective coating for improved light in-coupling. Our study sets the baseline for fabricating efficient perovskite/CIS TSCs, paving the way for future developments that might push the efficiencies to over 30%., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: Limited English proficiency (LEP) is common among hospitalized patients and may impact care. We synthesized the literature comparing clinical outcomes after in-hospital care for English-proficient(EP) versus LEP patients., Methods: This systematic review searched PubMed, Embase, and Web of Science from database inception through June 7, 2020, to identify research investigating clinical outcomes in patients receiving hospital-based care (in the emergency department, inpatient ward, surgical/procedural suite, or intensive care unit) that compared patients with LEP to an EP group. We assessed mortality, length of stay (LOS), readmissions/revisits, and complications. Study quality was evaluated using the Newcastle-Ottawa Scale., Results: Twenty-six studies met eligibility criteria. Study settings and populations were heterogeneous. Determination of primary language varied; a majority of studies (16/26) used patient self-report directly or via hospital records. Of 16 studies examining LEP and all-cause mortality, 13 found no significant association. Of 17 studies measuring LOS, 9 found no difference, 4 found longer LOS, 3 found shorter LOS, and 1 had mixed LOS results among patients with LEP. Several investigations suggested that LOS differences may be mediated at the hospital level. Nine studies evaluated inpatient readmissions. Among patients with LEP, there was evidence for increased readmissions in the setting of chronic medical conditions such as heart failure, but no evidence for increased readmissions among cohorts undergoing surgeries/procedures or with acute medical conditions. Five studies evaluated complications or harm related to a hospitalization, and no differences were found between language groups., Discussion: The research community lacks a standardized definition of LEP. Most studies did not find an association between English proficiency and mortality or complications. LOS findings were mixed and may be influenced at the hospital level. Differences in readmissions by language were concentrated in chronic medical conditions. Given the paucity of studies examining LEP populations, additional research is imperative., Prospero Registration Number: CRD42020143477., (© 2022. The Author(s) under exclusive licence to Society of General Internal Medicine.)