Search

Galaxies in voids have experienced a different environment than those in denser environments during their entire existence. Their properties are possibly different from galaxies in denser media. The CO-CAVITY project aims at studying the molecular gas contents of void galaxies and compare with non-void ones. To this end, 106 galaxies drawn from the mother CAVITY Integral Field Unit (IFU) sample have been observed with the EMIR receiver at the IRAM 30m telescope in Pico Veleta targeting the CO(1–0) and CO(2–1) lines. The data gathered allows deriving the star formation efficiency, molecular-to-atomic gas mass ratio and molecular-to-stellar mass ratio. The preliminary results presented here suggest that in general, there are no significant differences (within the errors) in the molecular gas content of void and control samples, although some deviations are observed in certain ranges when splitting the samples in stellar mass bins.

It is broadly accepted that CO is a reliable tracer of H2 in massive IR (LIR ≳ 109 L⊙) galaxies, and that there are clear correlations between LIR and L’CO that are qualitatively independent of environment and even redshift. We present two tales on the search for 12CO emission from dusty star-forming galaxies in both field (Lockman Hole, z < 0.1) and cluster (Zw Cl0024.1+1652, z ∼ 0.4) environments, according to the capabilities of the EMIR receiver at the IRAM-30m telescope. The observed galaxies are part of two follow-up programs in the millimetre regime of the spectroscopic Lockman-SpReSO and GLACE surveys in the optical (OSIRIS / 10.4m GTC). From these data we derived LIR and L’CO estimations and put them in the framework of the historic records according to the literature for each environmental case. We provide insights about some practical limits of the current facilities (IRAM observatories, ALMA, LMT) to get reliable estimations for IR at low and intermediate redshifts. Our results suggest that the amount of cold gas and the star formation efficiency increase with the cluster-centric distance, hence pointing to an environmental dependency.

BACKGROUND: Surgeons have come under increased scrutiny for postoperative pain management, particularly for opioid prescribing. To decrease opioid use but still provide pain control, nonopioid medications such as muscle relaxants are being used, which can be harmful in older adults. However, the prevalence of muscle relaxant prescribing, trends in use over time, and risk of prolonged use are unknown. STUDY DESIGN: Using a 20% representative Medicare sample, we conducted a retrospective analysis of muscle relaxant prescribing to patients ≥ 65 years of age. We merged patient data from Medicare Carrier, MedPAR, and Outpatient Files with Medicare Part D for the years 2013-2018. A total of 14 surgical procedures were included to represent a wide range of anatomic regions and specialties. RESULTS: The study cohort included 543,929 patients. Of the cohort, 8111 (1.5%) received a new muscle relaxant prescription at discharge. Spine procedures accounted for 12% of all procedures but 56% of postoperative prescribing. Overall, the rate of prescribing increased over the time period (1.4-2.0%, p < 0.001), with increases in prescribing primarily in the spine (7-9.6%, p < 0.0001) and orthopedic procedure groups (0.9-1.4%, p < 0.0001). Of patients discharged with a new muscle relaxant prescription, 10.7% had prolonged use. CONCLUSIONS: The use of muscle relaxants in the postoperative period for older adults is low, but increasing over time, especially in ortho and spine procedures. While pain control after surgery is crucial, surgeons should carefully consider the risks of muscle relaxant use, especially for older adults who are at higher risk for medication-related problems.

BACKGROUND: Geriatric trauma patients are an increasing population of the United States (US), sustaining a high incidence of falls, and suffer greater morbidity and mortality to their younger counterparts. Significant variation and challenges exist to optimize outcomes for this cohort, while being mindful of available resources. This manuscript provides concise summary of locoregional and national practices, including relevant updates in the triage of geriatric trauma in an effort to synthesize the results and provide guidance for further investigation. METHODS: We conducted a review of geriatric triage in the United States (US) at multiple stages in the care of the older patient, evaluating existing literature and guidelines. Opportunities for improvement or standardization were identified. RESULTS: Opportunities for improved geriatric trauma triage exist in the pre-hospital setting, in the trauma bay, and continue after admission. They may include physiologic criteria, biochemical markers, radiologic criteria and even age. Recent Trauma Quality Improvement Program (TQIP) Best Practices Guidelines for Geriatric Trauma Management published in 2024 support these findings. CONCLUSION: Trauma systems must adjust to provide optimal care for older adults. Further investigation is required to provide pertinent guidance.

We use new survey data from 1,203 households in rural Eastern India to estimate cross-sectional models of overall energy use and embedded emissions. Findings indicate that the primary driver of household energy use is household size and affluence. This is unsurprising and consistent with findings from the engineering literature on energy demand. However, there is also a substantial and significant moderating influence of skills on energy use. For emissions, we observe a bifurcated relationship in line with educational attainment. For those that have completed secondary education or more, skills are negatively associated with energy use and emissions, whereas for those with lesser qualifications more skills are associated with more energy use and emissions. The results are consistent with the environmental Kuznets curve, which implies that a critical level of affluence is required before environmental impacts start lessening. The results also echo a sociological critique of human capital theory - that individual abilities are not productive in and of themselves, but rather in relation to socially determined opportunity structures. Our findings show that this could also hold for greenhouse gas emissions.

Federica Recine, Alberto Bongiovanni, Nada Riva, Valentina Fausti, Alessandro De Vita, Laura Mercatali, Chiara Liverani, Giacomo Miserocchi, Dino Amadori, Toni Ibrahim Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy Abstract: Soft tissue sarcomas (STS) represent a variety of tumors of mesenchymal origin, accounting for about 1% of all adult cancers. This group of tumors comprises over 60 different histotypes with different biology showing different sensitivity to therapeutic agents. For decades, the standard first-line systemic treatment of metastatic STS has comprised anthracycline based-chemotherapy. Second-line therapy options include agents such as ifosfamide, gemcitabine, and pazopanib, but the optimal sequential therapy for the management of metastatic disease has yet to be defined. Trabectedin is one of the new molecules approved for patients in progression after first-line chemotherapy with anthracyclines or for those unfit for these agents. The compound is characterized by multiple potential mechanisms of action combining cytotoxic, targeted, and immunological effects. This article takes an in-depth look at the role of trabectedin in the management of metastatic STS, including L-sarcoma and non-L-sarcoma. Keywords: soft tissue sarcoma, histotypes, chemotherapy, L-sarcomas, non-L-sarcomas

Stefano Severi,1 Ilaria Grassi,1 Silvia Nicolini,1 Maddalena Sansovini,1 Alberto Bongiovanni,2 Giovanni Paganelli1 1Nuclear Medicine Unit, 2Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy Abstract: Peptide receptor radionuclide therapy (PRRT), developed over the last two decades, is carried out using radiopharmaceuticals such as 90Y-DOTA-Tyr3-octreotide and 177Lu-DOTA-Tyr3-octreotate (177Lu-Dotatate). These radiocompounds are obtained by labeling a synthetic somatostatin analog with a β-emitting radioisotope. The compounds differ from each other in terms of their energetic features (due to the radionuclide) and peptide receptor affinity (due to the analog) but share the common characteristic of binding specific membrane somatostatin receptors that are (generally) overexpressed in neuroendocrine neoplasms (NENs) and their metastases. NENs are tumors arising from diffuse neuroendocrine system cells that are classified according to grading based on Ki67 percentage values (Grades 1 and 2 are classed as neuroendocrine tumors [NETs]) and to the anatomical site of occurrence (in this paper, we only deal with gastroenteropancreatic [GEP]-NETs, which account for 60%–70% of all NENs). They are also characterized by specific symptoms such as diarrhea and flushing (30% of cases). Despite substantial experience gained in the area of PRRT and its demonstrable effects in terms of efficacy, safety, and improvement in quality of life, these compounds are still not registered (registration of 177Lu-Dotatate for the treatment of midgut NETs is expected soon). Thus, PRRT can only be used in experimental protocols. We provide an overview of the work of leading groups with wide-ranging experience and continuity in data publication in the area of GEP-NET PRRT and report our own personal experience of using different dosage schedules based on the presence of kidney and bone marrow risk factors. Our results on the retreatment of patients previously administered 90Y-DOTA-Tyr3-octreotide with a low dosage of 177Lu-Dotatate are also included. A comment on potential future developments of PRRT in GEP-NETs is provided. Keywords: 90Y-Dotatoc, 177Lu-Dotatate, radiopharmaceutical, radiolabelled receptors, neuroendocrine malignancies, delivered activity

Alessandro De Vita,1 Laura Mercatali,1 Federica Recine,1 Federica Pieri,2 Nada Riva,1 Alberto Bongiovanni,1 Chiara Liverani,1 Chiara Spadazzi,1 Giacomo Miserocchi,1 Dino Amadori,1 Toni Ibrahim1 1Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, 2Pathology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy Abstract: Sarcomas are a heterogeneous group of mesenchymal tumors arising from soft tissue or bone, with an uncertain etiology and difficult classification. Soft tissue sarcomas (STSs) account for around 1% of all adult cancers. Till date, more than 50 histologic subtypes have been identified. Adipocyte sarcoma or liposarcoma (LPS) is one of the most common STS subtypes, accounting for 15% of all sarcomas, with an incidence of 24% of all extremity STSs and 45% of all retroperitoneal STSs. The new World Health Organization classification system has divided LPS into four different subgroups: atypical lipomatous tumor/well-differentiated LPS, dedifferentiated LPS, myxoid LPS, and pleomorphic LPS. These lesions can develop at any location and exhibit different aggressive potentials reflecting their morphologic diversity and clinical behavior. Patients affected by LPS should be managed in specialized multidisciplinary cancer centers. Whereas surgical resection is the mainstay of treatment for localized disease, the benefits of adjuvant and neoadjuvant chemotherapy are still unclear. Systemic treatment, particularly chemotherapy, is still limited in metastatic disease. Despite the efforts toward a better understanding of the biology of LPS, the outcome of advanced and metastatic patients remains poor. The advent of targeted therapies may lead to an improvement of treatment options and clinical outcomes. A larger patient enrollment into translational and clinical studies will help increase the knowledge of the biological behavior of LPSs, test new drugs, and introduce new methodological studies, that is, on treatment response. Keywords: liposarcomas, adipocytic sarcomas, classification, management

BACKGROUND: Prescribing non-opioid pain medications, such as non-steroidal anti-inflammatory (NSAIDs) medications, has been shown to reduce pain and decrease opioid use, but it is unclear how to effectively encourage multimodal pain medication prescribing for hospitalised patients. Therefore, the aim of this study is to evaluate the effect of prechecking non-opioid pain medication orders on clinician prescribing of NSAIDs among hospitalised adults. METHODS: This was a cluster randomised controlled trial of adult (≥18 years) hospitalised patients admitted to three hospital sites under one quaternary hospital system in the USA from 2 March 2022 to 3 March 2023. A multimodal pain order panel was embedded in the admission order set, with NSAIDs prechecked in the intervention group. The intervention group could uncheck the NSAID order. The control group had access to the same NSAID order. The primary outcome was an increase in NSAID ordering. Secondary outcomes include NSAID administration, inpatient pain scores and opioid use and prescribing and relevant clinical harms including acute kidney injury, new gastrointestinal bleed and in-hospital death. RESULTS: Overall, 1049 clinicians were randomised. The study included 6239 patients for a total of 9595 encounters. Both NSAID ordering (36 vs 43%, p

BACKGROUND: For patients who may permanently or temporarily lose their ability to communicate preferences, advance care planning is a critical mechanism to guide medical decision-making but is currently underused among surgical patients. METHODS: A resident-led quality improvement project, including education and performance measurement, was conducted on an emergency general surgery service to increase the completion of inpatient advance care planning notes using a specialized template in the electronic health record. Advance care planning documentation was defined as either preadmission advance care planning documentation (eg, advance directive) or inpatient advance care planning (use of the electronic health record template). Data from patients admitted to the emergency general surgery service for 12+ hours were analyzed, and baseline data (July 2020 to June 2021) were compared with data from the intervention period (July 2021 to June 2022). The chart review evaluated the content of the inpatient advance care planning documentation from the intervention period. RESULTS: The frequency of inpatient advance care planning documentation increased (9.3%, n = 56 to 16.6%, n = 92, P < .001) with a greater contribution of inpatient advance care planning notes by the surgery team (16.7% to 55.4%) in the intervention period. Content analysis indicated that 79.0% of inpatient advance care planning notes listed preferences for life-sustaining therapy, 78.3% listed surrogacy, 57.3% listed overall health goals, and 50.3% listed treatment goals specific to the surgical encounter. CONCLUSION: Although a resident-led quality improvement project contributed to greater adoption of standardized inpatient advance care planning documentation on an emergency general surgery service, progress was slow, and integration into standard work was not achieved. Future efforts are needed to better understand the integration of essential advance care planning elements into workflows and to establish inclusive educational programming to prepare all team members for conducting and documenting advance care planning conversations.

Abstract Extracellular vesicles (EVs) are membrane-enclosed bio-nanoparticles secreted by cells and naturally evolved to transport various bioactive molecules between cells and even organisms. These cellular objects are considered one of the most promising bio-nanovehicles for the delivery of native and exogenous molecular cargo. However, many challenges with state-of-the-art EV-based candidates as drug carriers still exist, including issues with scalability, batch-to-batch reproducibility, and cost-sustainability of the final therapeutic formulation. Microalgal extracellular vesicles, which we named nanoalgosomes, are naturally released by various microalgal species. Here, we evaluate the innate biological properties of nanoalgosomes derived from cultures of the marine microalgae Tetraselmis chuii, using an optimized manufacturing protocol. Our investigation of nanoalgosome biocompatibility in preclinical models includes toxicological analyses, using the invertebrate model organism Caenorhabditis elegans, hematological and immunological evaluations ex vivo and in mice. We evaluate nanoalgosome cellular uptake mechanisms in C. elegans at cellular and subcellular levels, and study their biodistribution in mice with accurate space-time resolution. Further examination highlights the antioxidant and anti-inflammatory bioactivities of nanoalgosomes. This holistic approach to nanoalgosome functional characterization demonstrates that they are biocompatible and innate bioactive effectors with unique bone tropism. These findings suggest that nanoalgosomes have significant potential for future therapeutic applications.

Alberto Bongiovanni,1 Nada Riva,1 Marianna Ricci,1 Chiara Liverani,1 Federico La Manna,1 Alessandro De Vita,1 Flavia Foca,2 Laura Mercatali,1 Stefano Severi,3 Dino Amadori,4 Toni Ibrahim1 1Osteoncology and Rare Tumors Center, 2Unit of Biostatistics and Clinical Trials, 3Nuclear Medicine Unit, 4Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy Background and aim: To investigate the efficacy of platinum-based chemotherapy in patients with metastatic gastroenteropancreatic neuroendocrine carcinoma (mGEP-NEC) and define predictive and prognostic factors. Methods: Twenty mGEP-NEC patients were treated with cisplatin or carboplatin/etoposide between April 2010 and October 2014. Both large-cell and small-cell histologies were included. Cisplatin 25 mg/m2 was administered on days 1–3 followed by etoposide 100 mg/m2 on days 1–3 every 21 days. Carboplatin 300 mg/m2 was administered on day 1 followed by etoposide 100 mg/m2 on days 1–3. Results: Of the 19 evaluable patients, 13 obtained a partial response, four showed stable disease, and two progressed. Median overall survival (mOS) was 13.5 months and median progression-free survival (mPFS) was 10.9 months. Gallium-68 positron emission tomography/computerizsed tomography-positive patients had a higher, albeit not significantly, OS than those with negative results (75% vs 34.3% at 18 months; P=0.06). mPFS was 19.3 and 6.3 months (P55%, respectively. mOS was 8.1 months in the latter group but was not reached in the Ki67 ≤55% group (P-value =0.039). Patients with a lower body mass index (BMI) had a better prognosis in terms of both OS and PFS. Patients with BMI ≥25 had a mOS of 11.7 months (P=0.0293) and a mPFS of 6.2 months (P=0.0057). Conclusion: Platinum-based chemotherapy showed good efficacy in mGEP-NEC patients. Those with Ki67 ≤55%, positive Gallium-68 positron emission tomography/computerized tomography and BMI

Alberto Bongiovanni,1 Nada Riva,1 Sebastiano Calpona,1 Marianna Ricci,1 Erica Gunelli,1 Chiara Liverani,1 Federico La Manna,1 Alessandro De Vita,1 Manuela Monti,1 Stefano Severi,2 Federica Pieri,3 Elena Amadori,1 Riccardo Galassi,1 Davide Cavaliere,4 Alberto Zaccaroni,5 Andreas Tartaglia,6 Veronica Lunedei,7 Andrea Gardini,8 Laura Mercatali,1 Dino Amadori,1 Toni Ibrahim11Osteoncology and Rare Tumors Center, 2Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, 3Pathology Unit, 4Unit of Oncological Surgery and Advanced Therapies, 5Endocrine Surgery Unit, 6Endocrinology Unit, 7Gastroenterology and Digestive Endoscopy Unit, 8Department of General Surgery, Morgagni-Pierantoni Hospital, Forlì, ItalyBackground: We present a retrospective analysis of metronomic capecitabine in metastatic gastroenteropancreatic neuroendrocrine tumors (GEP-NETs). A review of the literature is also presented.Methods: From January 2007 to December 2013, ten patients with metastatic GEP-NETs (four pancreatic and six ileal) who progressed after treatment with somatostatin analogs and other cytotoxic agents received oral capecitabine 1,500 mg/day continuously. The median patient age was 68 (range 29–82) years. The median treatment duration was 8 months.Results: Five (50%) patients achieved a partial radiographic response, four (40%) showed stable disease, and one (10%) progressed. Median overall survival was 56 months. Three of the four pancreatic patients achieved a partial radiographic response that lasted for a median of 15.5 months; overall survival and progression-free survival in this subgroup was 58 and 6 months, respectively.Conclusion: Data in the literature show that capecitabine has only occasionally been used as a single agent, with increased toxicity. Only one study using single-agent capecitabine reported a progression-free survival of 9.9 months and overall survival of 36.5 months, without an objective response or major toxicity. In our experience, metronomic capecitabine was well tolerated, although minor side effects may have been underestimated due to the retrospective nature of our study. This regimen also seems to be feasible in elderly people. Although high response rates and prolonged response duration indicate the potential efficacy of this treatment, our results should be interpreted cautiously because of the small number of patients involved. Capecitabine was most effective in the pancreatic subgroup, which would seem to be more sensitive to chemotherapy.Keywords: capecitabine, gastroenteropancreatic neuroendocrine tumors, metronomic chemotherapy

BACKGROUND: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce pain and has become a core strategy to decrease opioid use, but there is a lack of data to describe encouraging use when admitting patients using electronic health record systems. OBJECTIVE: Assess an electronic health record system to increase ordering of NSAIDs for hospitalized adults. DESIGNS, SETTINGS AND PARTICIPANTS: We performed a cluster randomized controlled trial of clinicians admitting adult patients to a health system over a 9-month period. Clinicians were randomized to use a standard admission order set. INTERVENTION: Clinicians in the intervention arm were required to actively order or decline NSAIDs; the control arm was shown the same order but without a required response. MAIN OUTCOME AND MEASURES: The primary outcome was NSAIDs ordered and administered by the first full hospital day. Secondary outcomes included pain scores and opioid prescribing. RESULTS: A total of 20,085 hospitalizations were included. Among these hospitalizations, patients had a mean age of 58 years, and a Charlson comorbidity score of 2.97, while 50% and 56% were female and White, respectively. Overall, 52% were admitted by a clinician randomized to the intervention arm. NSAIDs were ordered in 2267 (22%) interventions and 2093 (22%) control admissions (p = .10). Similarly, there were no statistical differences in NSAID administration, pain scores, or opioid prescribing. Average pain scores (0-5 scale) were 3.36 in the control group and 3.39 in the intervention group (p = .46). There were no differences in clinical harms. CONCLUSIONS AND RELEVANCE: Requiring an active decision to order an NSAID at admission had no demonstrable impact on NSAID ordering. Multicomponent interventions, perhaps with stronger decision support, may be necessary to encourage NSAID ordering.

Marine microalgae offer significant potential as sustainably cultivable microorganisms for the biorefining of a diverse array of functional metabolites. In this study, three species of marine microalgae, Tetraselmis chuii Butcher CCAP 66/21B (Chlorophyte), Phaeodactylum tricornutum Bohlin CCAP 1052/1 (Diatom) and Amphidinium carterae Hulburt CCAP 1102/8 (Dinoflagellate), were batch cultivated and their biomass retrieved for analysis in terms of pigment and fatty acid composition as well as bioactivity potential. Sequential solvent maceration of the biomass returned extracts was used to determine antioxidant capacity and assess their growth inhibition potential against A549 (a human lung carcinoma) and MCF-7 (a breast carcinoma) cell lines. The extracts of A. carterae showed higher antioxidant capacity (≤ 33.5 μmol Trolox Equivalent mg Recovered Dried Material‒1) compared to the other extracts. No major cytotoxic activity nor production of reactive oxygen species was observed using the extracts of T. chuii and P. tricornutum. However, the methanolic extraction of A. carterae inhibited the growth of both A549 and MCF-7 cells (< 4%) at 25, 50 and 100 µg ml−1 concentrations, as determined using the MTS assay and AO/PI cell staining. Microalgal metabolites have the potential for practical applications in a variety of industrial sectors. The absence of toxicity and substantial antioxidant potential of extracts of T. chuii and P. tricornutum confirm their suitability for incorporation into animal feeds or human nutrition supplements. A. carterae also appears to be a promising source of bioactives that can be further valorized via multi-compound biorefinery pipelines.