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Heme trafficking is essential for cellular function, yet mechanisms of transport and/or heme interaction are not well defined. The System I and System II bacterial cytochrome c biogenesis pathways are developing into model systems for heme trafficking due to their functions in heme transport, heme stereospecific positioning, and mediation of heme attachment to apocytochrome c. Here we focus on the System II pathway, CcsBA, that is proposed to be a bi-functional heme transporter and holocytochrome c synthase. An extensive structure-function analysis of recombinantly expressed Helicobacter pylori and Campylobacter jejuni CcsBAs revealed key residues required for heme interaction and holocytochrome c synthase activity. Homologous residues were previously identified to be required for heme interaction in Helicobacter hepaticus CcsBA. This study provides direct, biochemical evidence that mechanisms of heme interaction are conserved, leading to the proposal that the CcsBA WWD heme-handling domain represents a novel target for therapeutics.
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Proteínas Bacterianas , Campylobacter jejuni , Helicobacter pylori , Hemo , Hemo/metabolismo , Helicobacter pylori/enzimología , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Campylobacter jejuni/enzimología , Campylobacter jejuni/genética , Campylobacter jejuni/metabolismo , Relación Estructura-Actividad , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Unión Proteica , Modelos Moleculares , LiasasRESUMEN
Delineation of cardiac substructures is crucial for a better understanding of radiation-related cardiotoxicities and to facilitate accurate and precise cardiac dose calculation for developing and applying risk models. This review examines recent advancements in cardiac substructure delineation in the radiation therapy (RT) context, aiming to provide a comprehensive overview of the current level of knowledge, challenges and future directions in this evolving field. Imaging used for RT planning presents challenges in reliably visualising cardiac anatomy. Although cardiac atlases and contouring guidelines aid in standardisation and reduction of variability, significant uncertainties remain in defining cardiac anatomy. Coupled with the inherent complexity of the heart, this necessitates auto-contouring for consistent large-scale data analysis and improved efficiency in prospective applications. Auto-contouring models, developed primarily for breast and lung cancer RT, have demonstrated performance comparable to manual contouring, marking a significant milestone in the evolution of cardiac delineation practices. Nevertheless, several key concerns require further investigation. There is an unmet need for expanding cardiac auto-contouring models to encompass a broader range of cancer sites. A shift in focus is needed from ensuring accuracy to enhancing the robustness and accessibility of auto-contouring models. Addressing these challenges is paramount for the integration of cardiac substructure delineation and associated risk models into routine clinical practice, thereby improving the safety of RT for future cancer patients.
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Background: Major depressive disorder (MDD) exhibits gender disparities, and emerging evidence suggests the involvement of the gut microbiome, necessitating exploration of sex-specific differences. Methods: A review was conducted, encompassing a thorough examination of relevant studies available in Medline via Ovid, Embase via OvidSP, CINAHL, and PsycINFO databases from their inception to June 2023. The search strategy employed specific keywords and Medical Subject Headings (MeSH) terms tailored to major depressive disorder in women, encompassing unipolar depression, depressive symptoms, and dysbiosis. Results: Five studies were included. Among the four studies, alterations in alpha (n=1) and beta diversity (n=3) in the gut microbiome of individuals with MDD were revealed compared to controls. Gender-specific differences were observed in four studies, demonstrating the abundance of specific bacterial taxa and highlighting potential sex-specific implications in MDD pathophysiology. Correlation analyses (n=4) indicated associations between certain bacterial taxa and the severity of depressive symptoms, with varying patterns between males and females. Studies (n=3) also highlighted promising findings regarding the potential utility of microbial markers in diagnosing MDD, emphasizing the crucial role of sex stratification in understanding the disease pathophysiology. Conclusions: The findings underscore the importance of recognizing gender-specific differences in the composition of the gut microbiome and its relationship with MDD. Further comprehensive robust studies are required to unravel the intricate mechanisms underlying these disparities.
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In this perspective paper, the findings of the recently published LUMINA study are critically evaluated, with an emphasis on the need for careful interpretation and a thoughtful approach in clinical practice. The LUMINA trial, which investigates the role of adjuvant endocrine therapy in low-risk breast cancer patients, is assessed for its limitations, including a highly selective patient cohort and an insufficient follow-up period. The importance of long-term data and further trials to inform clinical decisions effectively is emphasized. While the LUMINA study does not support an immediate change in practice, it is seen as a foundation for generating hypotheses to guide ongoing clinical trials. This important study has served as inspiration to develop this perspective paper, which takes into account ongoing studies and the toxicity profile of postoperative treatments in low-risk recurrence breast cancer. The need for a patient-cantered approach is stressed, considering individual wishes and desires in decision-making, despite the complexity of articulating these aspects in guidelines. A wise interpretation of available findings is essential to ensure sound clinical decision-making before broadly applying omission of radiation therapy.
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Neoplasias de la Mama , Mastectomía Segmentaria , Humanos , Femenino , Recurrencia Local de Neoplasia/cirugía , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/tratamiento farmacológico , Terapia CombinadaRESUMEN
Heme trafficking is a fundamental biological process, yet its direct study has been hampered due to heme's tight intracellular regulation, heme cytotoxicity, and the transient nature of trafficking. The bacterial System I and System II cytochrome c biogenesis pathways are developing into models to interrogate heme trafficking mechanisms, as they function to transport heme from inside to outside the cell for attachment to apocytochrome c. Cytochromes c require heme for folding and to function in the context of electron transport chains for critical cellular functions, such as respiration. We focus on System I, comprised of eight membrane proteins, CcmABCDEFGH, proposed to function in two steps: CcmABCD mediates the transfer of heme and attachment to CcmE. HoloCcmE chaperones heme to CcmFH for attachment to apocytochrome c. While CcmFH is known to be the holocytochrome c synthase, the mechanism of heme interaction and positioning for attachment to apocytochrome c remains to be elucidated. A comprehensive structure-function analysis of the conserved WWD domain in CcmF was undertaken utilizing alanine-scanning and cysteine-scanning, revealing residues critical for CcmF's synthase function and residues required for interaction with the 2- and 4-vinyls of heme. This analysis demonstrates for the first time that the CcmF WWD domain directly interacts with heme and that heme interactions within this domain are required for attachment to apocytochrome c. This in-depth interrogation of heme binding now allows for comparison across cytochrome c biogenesis proteins CcmF, CcmC, and CcsBA, revealing common mechanisms of heme interaction in these heme trafficking pathways.IMPORTANCEHeme is an essential co-factor for proteins involved with critical cellular functions, such as energy production and oxygen transport. Thus, understanding how heme interacts with proteins and is moved through cells is a fundamental biological question. This work studies the System I cytochrome c biogenesis pathway, which in some species (including Escherichia coli) is composed of eight integral membrane or membrane-associated proteins called CcmA-H that are proposed to function in two steps to transport and attach heme to apocytochrome c. Cytochrome c requires this heme attachment to function in electron transport chains to generate cellular energy. A conserved WWD heme-handling domain in CcmFH is analyzed and residues critical for heme interaction and holocytochrome c synthase activity are identified. CcmFH is the third member of the WWD domain-containing heme-handling protein family to undergo a comprehensive structure-function analysis, allowing for comparison of heme interaction across this protein family.
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STUDY OBJECTIVE: To understand variations and experiences of vaginal lengthening internationally in individuals with congenital underdevelopment of the uterus, cervix, and upper vagina or Müllerian agenesis METHODS: In this study, we used a cross-sectional mixed-methods design incorporating quantitative and qualitative questionnaires. Adults with Müllerian agenesis completed questionnaires with quantitative and open-ended qualitative questions about their vaginal lengthening experiences. Data were analyzed using descriptive statistics and inductive thematic analysis. RESULTS: Of 616 respondents meeting inclusion criteria (representing 40 countries), 46% (n = 284) reported no vaginal lengthening intervention. Vaginal lengthening was commonly reported by participants from North America and Europe (59%) and less commonly by participants from Africa, Asia, and South America (16%). Of those who had undergone vaginal lengthening, 72% reported dilator use, 34% coital dilation, and 39% surgery. Four major themes were identified in response to the open-ended vaginal lengthening experience question: (1) difficult physical symptoms, (2) practical and psychosocial challenges, (3) intimate relationships and sexual satisfaction, and (4) impact of experiences with healthcare providers. CONCLUSION: This study highlights vaginal lengthening practices internationally and shared themes related to significant challenges and positive experiences. The findings show room for improvement in the counseling and care surrounding vaginal lengthening. Future research should investigate factors that influence decision-making about vaginal lengthening and work toward international consensus on best care practices in Müllerian agenesis.
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Trastornos del Desarrollo Sexual 46, XX , Anomalías Congénitas , Adulto , Femenino , Humanos , Estudios Transversales , Resultado del Tratamiento , Vagina/cirugía , Vagina/anomalías , Útero , Trastornos del Desarrollo Sexual 46, XX/diagnóstico , Conductos Paramesonéfricos/cirugía , Conductos Paramesonéfricos/anomalías , Anomalías Congénitas/diagnósticoRESUMEN
Bare aluminum metal surfaces are highly reactive, which leads to the spontaneous formation of a protective oxide surface layer. Because many subsequent corrosive processes are mediated by water, the structure and dynamics of water at the oxide interface are anticipated to influence corrosion kinetics. Using molecular dynamics simulations with a reactive force field, we model the behavior of aqueous aluminum metal ions in water adsorbed onto aluminum oxide surfaces across a range of ion concentrations and water film thicknesses corresponding to increasing relative humidity. We find that the structure and diffusivity of both the water and the metal ions depend strongly on the humidity of the environment and the relative height within the adsorbed water film. Aqueous aluminum ion diffusion rates in water films corresponding to a typical indoor relative humidity of 30% are found to be more than 2 orders of magnitude slower than self-diffusion of water in the bulk limit. Connections between metal ion diffusivity and corrosion reaction kinetics are assessed parametrically with a reductionist model based on a 1D continuum reaction-diffusion equation. Our results highlight the importance of incorporating the properties specific to interfacial water in predictive models of aluminum corrosion.
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Aromatase inhibitor-induced arthralgia (AIA) contributes to poor adherence of aromatase inhibitor therapies in patients with breast cancer. A systematic review using network meta-analysis (NMA) was conducted to examine the clinical effectiveness of multiple therapies and rank probabilities for the management of AIA. Randomized controlled trials (RCTs) assessing treatments for AIA in postmenopausal women with stage 0-III hormone receptor-positive breast cancer were searched from inception to October 2021. The main NMA involved 1516 participants from 17 RCTs. Acupuncture was the highest ranked intervention to improve pain intensity followed by sham acupuncture, multicomponent herbal medicine, exercise, duloxetine, vitamin D, omega-3 fatty acids, physical therapy, testosterone, and inactive controls. Single natural products were inferior to controls. The current review provides new insights into the management of AIA in breast cancer survivors for increased survival and can be utilized to make evidence-based decisions regarding treatment.
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Inhibidores de la Aromatasa , Neoplasias de la Mama , Femenino , Humanos , Inhibidores de la Aromatasa/efectos adversos , Metaanálisis en Red , Artralgia/inducido químicamente , Artralgia/terapia , Resultado del Tratamiento , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inducido químicamenteRESUMEN
Oncoplastic breast surgery encompasses a range of techniques used to provide equitable oncological outcomes compared with standard breast surgery while, simultaneously, prioritizing aesthetic outcomes. While the outcomes of oncoplastic breast surgery are promising, it can add an extra complexity to the treatment paradigm of breast cancer and impact on decision-making surrounding adjuvant therapies, like chemotherapy and radiotherapy. As such, early discussions at the multidisciplinary team meeting with surgeons, medical oncologists, and radiation oncologists present, should be encouraged to facilitate best patient care.
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OBJECTIVE: Around 30% of people with long-term physical health conditions (LTCs) experience comorbid anxiety and depression. For many, comorbid distress is linked to difficulties adjusting to the challenges of the LTC. The aims of this article are to present a transdiagnostic theoretical model of adjustment to LTCs (TMA-LTC), demonstrate the application of this model in clinical practice, and highlight the distinguishing features of treating LTC-related distress compared with treating primary anxiety and/or depression. METHODS: A systematic review (k = 21) was conducted to collate preexisting evidence-based models of adjustment across LTCs. Models of adjustment for a range of LTCs were extracted and synthesized into a new preliminary TMA-LTC. Two expert consensus meetings were held, where experts rated the relevance and importance of all concepts within the models. RESULTS: The TMA-LTC proposes that acute critical events or ongoing illness stressors can disrupt emotional equilibrium, and that whether a person returns to equilibrium and achieves good psychological adjustment depends on a number of cognitive and behavioral factors, as well as their interpersonal, intrapersonal, environmental, and illness-specific contexts. A case study is presented to demonstrate the clinical application of this model in treating illness-related distress, highlighting how it overcomes roadblocks that may be encountered when working primarily within traditional mental health paradigms. CONCLUSIONS: As an empirically and clinically informed model, TMA-LTC provides a useful guide for assessment, formulation, and treatment in the context of psychological adjustment to LTCs. Future studies are needed to test treatments that have been developed based on TMA-LTC.
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Ansiedad , Ajuste Emocional , Trastornos de Ansiedad , Comorbilidad , Humanos , Salud MentalRESUMEN
INTRODUCTION: Aimed to develop a simple and robust volumetric modulated arc radiotherapy (VMAT) solution for comprehensive lymph node (CLN) breast cancer without increase in low-dose wash. METHODS: Forty CLN-breast patient data sets were utilised to develop a knowledge-based planning (KBP) VMAT model, which limits low-dose wash using iterative learning and base-tangential methods as benchmark. Another twenty data sets were employed to validate the model comparing KBP-generated ipsilateral VMAT (ipsi-VMAT) plans against the benchmarked hybrid (h)-VMAT (departmental standard) and bowtie-VMAT (published best practice) methods. Planning target volume (PTV), conformity/homogeneity index (CI/HI), organ-at-risk (OAR), remaining-volume-at-risk (RVR) and blinded radiation oncologist (RO) plan preference were evaluated. RESULTS: Ipsi- and bowtie-VMAT plans were dosimetrically equivalent, achieving greater nodal target coverage (P < 0.05) compared to h-VMAT with minor reduction in breast coverage. CI was enhanced for a small reduction in breast HI with improved dose sparing to ipsilateral-lung and humeral head (P < 0.05) at immaterial expense to spinal cord. Significantly, low-dose wash to OARs and RVR were comparable between all plan types demonstrating a simple VMAT class solution robust to patient-specific anatomic variation can be applied to CLN breast without need for complex beam modification (hybrid plans, avoidance sectors or other). This result was supported by blinded RO review. CONCLUSIONS: A simple and robust ipsilateral VMAT class solution for CLN breast generated using iterative KBP modelling can achieve clinically acceptable target coverage and OAR sparing without unwanted increase in low-dose wash associated with increased second malignancy risk.
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Oncología por Radiación , Radioterapia de Intensidad Modulada , Humanos , Bases del Conocimiento , Órganos en Riesgo , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodosRESUMEN
INTRODUCTION: Until late 2018, standard of practice at the Northern Sydney Cancer Centre (NSCC) for breast and nodal treatment was a conformal mono-isocentric technique. A planning study comparing an existing mono-isocentric three-dimensional conformal radiotherapy (3D-CRT) planning technique to a hybrid intensity-modulated radiotherapy (hIMRT) approach for the whole breast and supraclavicular fossa (SCF) region was undertaken with the aim to improve plan quality by improving dose conformity/homogeneity across target volumes and reducing hotspots outside the target. METHODS: A cohort of 17 patients was retrospectively planned using the proposed hIMRT technique, keeping the same planning constraints as the original treated breast and SCF 3D-CRT plan and normalising the 3D-CRT plans to achieve minimum breast/SCF target coverage to compare organs at risk (OARs). Normal tissue index (NTI) and homogeneity index (HI) were compared for plan quality as well as for evaluating OARs. RESULTS: The hIMRT technique showed statistically significant improvements in NTI and HI, as well as improvement in maximum brachial plexus and thyroid doses. There was a negligible increase in maximum oesophagus dose which could be improved if used in optimisation. Other OAR doses in the irradiated region were comparable to the 3D-CRT plans, however maximum doses were reduced overall. CONCLUSION: The hIMRT planning technique maintained clinically acceptable doses to OARs and reduced normal tissue dose while maintaining equivalent dose coverage to breast and SCF planning target volumes with improved conformity and homogeneity. The reduction in maximum doses promotes a favourable toxicity profile, with potential benefit of improved long-term cosmesis.
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Radioterapia Conformacional , Radioterapia de Intensidad Modulada , Humanos , Técnicas de Planificación , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Estudios RetrospectivosRESUMEN
Increasing evidence suggests that the gut microbiome is associated with both cancer chemotherapy (CTX) outcomes and adverse events (AEs). This review examines the relationship between the gut microbiome and CTX as well as the impact of CTX on the gut microbiome. A literature search was conducted in electronic databases Medline, PubMed and ScienceDirect, with searches for "cancer" and "chemotherapy" and "microbiome/microbiota". The relevant literature was selected for use in this article. Seventeen studies were selected on participants with colorectal cancer (CRC; n=5), Acute Myeloid Leukemia (AML; n=3), Non-Hodgkin's lymphoma (n=2), breast cancer (BCa; n=1), lung cancer (n=1), ovarian cancer (n=1), liver cancer (n=1), and various other types of cancers (n=3). Seven studies assessed the relationship between the gut microbiome and CTX with faecal samples collected prior to (n=3) and following CTX (n=4) showing that the gut microbiome is associated with both CTX efficacy and toxicity. Ten other prospective studies assessed the impact of CTX during treatment and found that CTX modulates the gut microbiome of people with cancer and that dysbiosis induced by the CTX is related to AEs. CTX adversely impacts the gut microbiome, inducing dysbiosis and is associated with CTX outcomes and AEs. Current evidence provides insights into the gut microbiome for clinicians, cancer survivors and the general public. More research is required to better understand and modify the impact of CTX on the gut microbiome.
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Background: Emerging evidence suggests that gut microbiota influences the clinical response to immunotherapy. This review of clinical studies examines the relationship between gut microbiota and immunotherapy outcomes. Method: A literature search was conducted in electronic databases Medline, PubMed and ScienceDirect, with searches for "cancer" and "immunotherapy/immune checkpoint inhibitor" and "microbiome/microbiota" and/or "fecal microbiome transplant FMT". The relevant literature was selected for this article. Results: Ten studies examined patients diagnosed with advanced metastatic melanoma (n = 6), hepatocellular carcinoma (HCC) (n = 2), non-small cell lung carcinoma (NSCLC) (n = 1) and one study examined combination both NSCLC and renal cell carcinoma (RCC) (n = 1). These studies consistently reported that the gut microbiome profile prior to administering immune checkpoint inhibitors (ICIs) was related to clinical response as measured by progression-free survival (PFS) and overall survival (OS). Two studies reported that a low abundance of Bacteroidetes was associated with colitis. Two studies showed that patients with anti-PD-1 refractory metastatic melanoma experienced improved response rates and no added toxicity when receiving fecal microbiota transplant (FMT) from patients with anti-PD-1 responsive disease. Conclusions: Overall, significant differences in the diversity and composition of the gut microbiome were identified in ICIs responders and non-responders. Our findings provide new insights into the value of assessing the gut microbiome in immunotherapy. Further robust randomized controlled trials (RCTs) examining the modulatory effects of the gut microbiome and FMT on ICIs in patients not responding to immunotherapy are warranted.
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PURPOSE: The information women receive about the type and timing of breast reconstruction (BR) from healthcare providers is crucial to help them make an informed decision, and this is particularly important in complex cases and/or high-risk cases. This study sought to provide qualitative insights into Australian women's BR decision-making experiences. METHOD: Twenty-nine women who had received a mastectomy and made decisions about BR, including the type (expander, implant and/or autologous) and timing (immediate, delayed or immediate-delayed), participated in semi-structured telephone interviews. Interviews were analysed thematically using the Framework method. RESULTS: Seven themes were identified: 1) information provision and needs; 2) values and preferences; 3) pressure to decide; 4) feasibility (e.g. clinical and/or financial factors); 5) social influence and support; 6) multidisciplinary team and organisational structures; and 7) decision implementation and outcomes. Breast care nurse support, as well as collaboration and communication within multidisciplinary teams were perceived by women as facilitating the BR decision-making process. CONCLUSIONS: The identified themes offer an in-depth explanation of how a sample of Australian women make BR decisions. The current findings highlight the often limited clinician-patient information-sharing and demonstrate the overarching influence of the multidisciplinary medical team and organisational structures on BR decision-making. Development of in-consult decision-aids and strategies to improve multidisciplinary care are discussed.
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Neoplasias de la Mama , Mamoplastia , Australia , Neoplasias de la Mama/cirugía , Toma de Decisiones , Femenino , Humanos , MastectomíaRESUMEN
Supportive cancer care services, including acupuncture and Tai Chi and Qigong (TQ), are offered to cancer patients to manage cancer symptoms and/or treatment-related adverse effects and improve quality of life during and after standard care. Normal face-to-face acupuncture and TQ group services were suspended during the coronavirus (COVID-19) pandemic to reduce the risk of transmission of infection and meet social distancing restriction guidelines. This led to a sudden shift from face-to-face sessions to telehealth sessions in the health care system. We report patients' experiences of TQ telehealth services as a new initiative developed for cancer care. We found that delivery of TQ telehealth is feasible and resulted in increased overall patient satisfaction with cancer care services during the lockdown. The delivery of TQ telehealth experiences and challenges are discussed.
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BACKGROUND: Gastrointestinal (GI) toxicities are common adverse effects of pelvic radiotherapy (RT). Several recent studies revealed that toxicity of RT is associated with dysbiosis of the gut microbiome. METHOD: A literature search was conducted in electronic databases Medline, PubMed, and ScienceDirect, with search terms "microbiome and/or microbiota" and "radiotherapy (RT) and/or chemoradiation therapy (CRT)" and "cancer", and the relevant literature were selected for use in this article. RESULTS: Eight prospective cohort studies were selected for review with a total of 311 participants with a range of 15-134 participants within these studies. The selected studies were conducted in patients with gynaecological (n = 3), rectal (n = 2), or prostate cancers (n = 1), or patients with various types of malignancies (n = 2). Three studies reported that cancer patients had significantly lower alpha diversity compared with healthy controls. Seven studies found that lower alpha diversity and modulated gut microbiome were associated with GI toxicities during and after pelvic RT (n = 5) and CRT (n = 2), whereas one study found that beta diversity was related to a complete response following CRT. Two further studies reported that fatigue was associated with dysbiosis of the gut microbiome and low alpha diversity during and after RT, and with dysbiosis of the gut microbiome and diarrhoea, respectively. CONCLUSION: Gut microbiome profiles are associated with GI toxicities and have the potential to predict RT/CRT-induced toxicities and quality of life (QoL) in patients undergoing those treatments. Further robust randomized controlled trials (RCTs) are required to elucidate the effect of gut microbiome profiles on RT-related adverse effects and responses to RT.
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PURPOSE: Our purpose was to report outcomes of a novel palliative radiation therapy protocol that omits computed tomography simulation and prospectively collects electronic patient-reported outcomes (ePROs). METHODS AND MATERIALS: Patients receiving extracranial, nonstereotactic, linear accelerator-based palliative radiation therapy who met inclusion criteria (no mask-based immobilization and a diagnostic computed tomography within 4 weeks) were eligible. Global pain was scored with the 11-point numerical pain rating scale (NPRS). Patients were coded as having osseous or soft tissue metastases and no/mild versus severe baseline pain (NPRS ≥ 5). Pain response at 4 weeks was measured according to the international consensus (no analgesia adjustment). Transition to ePRO questionnaires was completed in 3 phases. Initially, pain assessments were collected on paper for 11 months, then pilot ePROs for 1 month and then, after adjustments, revised ePROs from 1 year onwards. ePRO feasibility criteria were established with reference to the paper-based process and published evidence. RESULTS: Between May 2018 and November 2019, 542 consecutive patients were screened, of whom 163 were eligible (30%), and 160 patients were successfully treated. The proportion of patients eligible for the study improved from approximately 20% to 50% by study end. Routine care pain monitoring via ePROs was feasible. One hundred twenty-seven patients had a baseline NPRS recording. Ninety-five patients had osseous (61% severe pain) and 32 had soft tissue (25% severe pain) metastases. Eighty-four patients (66%) were assessable for pain response at 4 weeks. In the 41 patients with severe osseous pain, overall and complete pain response was 78% and 22%, respectively. CONCLUSIONS: By study completion, 50% of patients receiving palliative extracranial radiation therapy avoided simulation, streamlining the treatment process and maximizing patient convenience. Pain response for patients with severe pain from osseous lesions was equivalent to published evidence.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which is an ongoing global health concern. The exact source of the virus has not been identified, but it is believed that this novel coronavirus originated in animals; bats in particular have been implicated as the primary reservoir of the virus. SARS-CoV-2 can also be transmitted from humans to other animals, including tigers, cats, and mink. Consequently, infected people who work directly with bats could transfer the virus to a wild North American bat, resulting in a new natural reservoir for the virus, and lead to new outbreaks of human disease. We evaluated a reverse-transcription real-time PCR panel for detection of SARS-CoV-2 in bat guano. We found the panel to be highly specific for SARS-CoV-2, and able to detect the virus in bat guano samples spiked with SARS-CoV-2 viral RNA. Our panel could be utilized by wildlife agencies to test bats in rehabilitation facilities prior to their release to the wild, minimizing the risk of spreading this virus to wild bat populations.