The Musculoskeletal Tumor Society Scoring system is a valid subjective and objective tool to evaluate outcomes of surgical treatment of patients affected by upper and lower extremity tumors.

PURPOSE: The main purpose of the present study was to evaluate if there is a difference between objective or subjective administration of the MSTS score in a cohort of patients affected by musculoskeletal oncological diseases. MATERIALS AND METHODS: All patients who underwent surgery for bone or soft tissue localization of neoplastic disease in lower or upper limb from June 2015 to June 2020 were considered eligible. In order to administer the score as a PROM, the MSTS was first translated and cross-culturally adapted in Italian. During follow up visits, all patients filled out Italian versions of SF36, TESS and MSTS. Psychometric properties of the Italian version of MSTS were analyzed. Correlation between objective and self-administered MSTS score was assessed through Pearson's coefficient. RESULTS: A finale sample of 110 patients were included: 59 affected by lower extremity involvement and 51 affected by upper extremity involvement. The Italian version of the MSTS score showed good psychometric properties for both lower and upper extremity. The correlation between self-administered and hetero-administered version of the questionnaire was as high as r = 0.97 for lower extremities and r = 0.96 for upper extremities. CONCLUSIONS: The Italian version of the MSTS is a valid tool to evaluate outcomes of surgical treatment of patients affected by extremities tumors and it can be used as a subjective tool for both lower and upper extremity.

Discontinuation rate and serious adverse events of chemoimmunotherapy as neoadjuvant treatment for triple-negative breast cancer: a systematic review and meta-analysis.

BACKGROUND: The use of combination of chemotherapy with immune checkpoint inhibitors (ICIs) has shown efficacy in triple-negative breast cancer (TNBC), and chemoimmunotherapy has been introduced in clinical practice. However, limited data are available on the discontinuation rate and serious adverse events of these treatments, particularly in the neoadjuvant setting. Herein, we carried out a comprehensive systematic review and meta-analysis to assess discontinuation rate and serious adverse events of chemoimmunotherapy compared to chemotherapy alone in phase II and III neoadjuvant clinical trials in TNBC. MATERIALS AND METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, EMBASE, Cochrane Library, and PubMed/Medline were searched for articles published from June 2008 to May 2023. The outcomes of interest were the discontinuation rate, serious adverse events, and grade 3-4 adverse events. RESULTS: Four studies were included in the analysis. The pooled odds ratios (ORs) for discontinuation rate and serious adverse events were 1.26 [95% confidence interval (CI) 0.78-2.06] and 1.79 (95% CI 1.4-2.28), respectively, in patients receiving chemoimmunotherapy compared to chemotherapy alone as neoadjuvant treatment for TNBC. The chemoimmunotherapy group had a higher risk of grade 3-4 adverse events (OR 1.30, 95% CI 1.07-1.59). The analysis showed substantial heterogeneity, and the risk of discontinuation rate was heavily influenced by the KEYNOTE-522 trial. CONCLUSIONS: Our findings highlight the need for clinical trials specifically focused on safety, quality of life, and treatment adherence in TNBC patients receiving neoadjuvant treatment. Close monitoring of tolerability remains crucial in this clinical setting.

Radiation measurements in the International Space Station, Columbus module, in 2020-2022 with the LIDAL detector.

The Light Ion Detector for ALTEA (LIDAL) is a new instrument designed to measure flux, energy spectra and Time of Flight of ions in a space habitat. It was installed in the International Space Station (Columbus) on January 19, 2020 and it is still operating. This paper presents the results of LIDAL measurements in the first 17 months of operation (01/2020-05/2022). Particle flux, dose rate, Time of Flight and spectra are presented and studied in the three ISS orthogonal directions and in the different geomagnetic regions (high latitude, low latitude, and South Atlantic Anomaly, SAA). The results are consistent with previous measurements. Dose rates range between 1.8 nGy/s and 2.4 nGy/s, flux between 0.21 particles/(sr cm2 s) and 0.32 particles/(sr cm2 s) as measured across time and directions during the full orbit. These data offer insights concerning the radiation measurements in the ISS and demonstrate the capabilities of LIDAL as a unique tool for the measurement of space radiation in space habitats, also providing novel information relevant to assess radiation risks for astronauts.

IN VIVO public monitoring in emergency exposure scenarios by means of spectrometric and non-spetrometric devices.

In a nuclear or radiological accident scenario, when potentially members of the public can undergo internal contamination by anthropogenic radionuclides released in the atmosphere, effective methods that can be used directly in the field to perform a fast scan for internal contamination on a large number of individuals can play a major role to undertake appropriate countermeasures. Specific attention should be paid to the individual monitoring of children since they constitute the sensitive population group with the highest risk of developing cancer. At the ENEA Casaccia Research Center in Rome (Italy), monitoring procedures based on a portable HPGe detector and ratemeters were tested in the field. A total of 170 acquisitions of uncontaminated volunteers for the blank measurements were collected, 105 acquisitions on adult and 65 acquisitions on 10-y/o children. The detection limit calculation, in terms of activity taken up (Bq), was carried out according to the Standard ISO's 11929 and 28218, whereas the corresponding 'minimum effective dose' (mSv) was calculated based on international commission on radiological protection (ICRP) Publications 134, 137 and 141. Results and evaluations of the measurement campaign are presented and discussed in respect to the aspects reported in the current literature.

Role of a corrugated Dion-Jacobson 2D perovskite as an additive in 3D MAPbBr3 perovskite-based light emitting diodes.

Metal halide perovskites represent an intriguing class of materials, and a very promising approach to tune the properties of optoelectronic devices and improve their performance involves the implementation of architectures based on mixed 3D and 2D perovskites. In this work, we investigated the use of a corrugated 2D Dion-Jacobson perovskite as an additive to a classical 3D MAPbBr3 perovskite for applications in light-emitting diodes. Taking advantage of the properties of this emerging class of materials, we studied the effect of a 2D 2-(dimethylamino)ethylamine (DMEN)-based perovskite on the morphological, photophysical, and optoelectronic properties of 3D perovskite thin films. We used α-DMEN perovskite both in a mixture with MAPbBr3 creating mixed 2D/3D phases and as a passivating thin layer deposited on the top of a 3D perovskite polycrystalline film. We observed a beneficial modulation of the thin film surface, a blue shift in the emission spectrum, and enhanced device performance.

PARP1 allows proper telomere replication through TRF1 poly (ADP-ribosyl)ation and helicase recruitment.

Telomeres are nucleoprotein structures at eukaryotic chromosome termini. Their stability is preserved by a six-protein complex named shelterin. Among these, TRF1 binds telomere duplex and assists DNA replication with mechanisms only partly clarified. Here we found that poly (ADP-ribose) polymerase 1 (PARP1) interacts and covalently PARylates TRF1 in S-phase modifying its DNA affinity. Therefore, genetic and pharmacological inhibition of PARP1 impairs the dynamic association of TRF1 and the bromodeoxyuridine incorporation at replicating telomeres. Inhibition of PARP1 also affects the recruitment of WRN and BLM helicases in TRF1 containing complexes during S-phase, triggering replication-dependent DNA-damage and telomere fragility. This work unveils an unprecedented role for PARP1 as a "surveillant" of telomere replication, which orchestrates protein dynamics at proceeding replication fork.

SARS-CoV-2 mRNA vaccine BNT162b2 triggers a consistent cross-variant humoral and cellular response.

As the SARS-CoV-2 pandemic continues to rage worldwide, the emergence of numerous variants of concern (VOC) represents a challenge for the vaccinal protective efficacy and the reliability of commercially available high-throughput immunoassays. Our study demonstrates the administration of two doses of the BNT162b2 vaccine that elicited a robust SARS-CoV-2-specific immune response which was assessed up to 3 months after full vaccination in a cohort of 37 health care workers (HCWs). SARS-CoV-2-specific antibody response, evaluated by four commercially available chemiluminescence immunoassays (CLIA), was qualitatively consistent with the results provided by the gold-standard in vitro neutralization assay (NTA). However, we could not observe a correlation between the quantity of the antibody detected by CLIA assays and their neutralizing activity tested by NTA. Almost all subjects developed a SARS-CoV-2-specific T-cell response. Moreover, vaccinated HCWs developed a similar protective neutralizing antibodies response against the EU (B.1), Alpha (B.1.1.7), Gamma (P.1), and Eta (B.1.525) SARS-CoV-2 variants, while Beta (B.1.351) and Delta (B.1.617.2) strains displayed a consistent partial immune evasion. These results underline the importance of a solid vaccine-elicited immune response and a robust antibody titre. We believe that these relevant results should be taken into consideration in the definition of future vaccinal strategies.

Hypothesis on the possible relevance of the immunogenic cell death in the treatment of gestational trophoblastic neoplasms.

The genetic background and the antigenic landscape of cancer cells play a critical role in the response to immunotherapies. A high tumor antigenicity, together with an increased adjuvanticity potentially induced by a peculiar type of cell death, namely immunogenic cell death (ICD), could foster the response to immunogenic therapies. The gestational trophoblastic neoplasm (GTN) is a one-of-a-kind cancer in the oncological landscape due to its exclusive genomic makeup. The prognosis of GTN is significantly better than non-gestational trophoblastic neoplasm (nGTN). Due to its peculiar genetic inheritance, GTN potentially constitutes a singular archetype in the immuno-oncological field.

Standard versus personalized schedule of regorafenib in metastatic gastrointestinal stromal tumors: a retrospective, multicenter, real-world study.

BACKGROUND: Despite its proven activity as third-line treatment in gastrointestinal stromal tumors (GIST), regorafenib can present a poor tolerability profile which often leads to treatment modifications and transient or permanent discontinuation; thus, in clinical practice physicians usually adopt various dosing and interval schedules to counteract regorafenib-related adverse events and avoid treatment interruption. The aim of this real-world study was to investigate the efficacy and safety of personalized schedules of regorafenib in patients with metastatic GIST, in comparison with the standard schedule (160 mg daily, 3-weeks-on, 1-week-off). PATIENTS AND METHODS: Institutional registries across seven Italian reference centers were retrospectively reviewed and data of interest retrieved to identify patients with GIST who had received regorafenib from February 2013 to January 2021. The Kaplan-Meier method was used to estimate survival and the log-rank test to make comparisons. RESULTS: Of a total of 152 patients with GIST, 49 were treated with standard dose, while 103 received personalized schedules. At a median follow-up of 36.5 months, median progression-free survival was 5.6 months [95% confidence interval (CI) 3.73-11.0 months] versus 9.7 months (95% CI 7.9-14.5 months) in the standard-dose and the personalized schedule groups, respectively [hazard ratio (HR) 0.51; 95% CI 0.34-0.75; P = 0.00052]. Median overall survival was 16.6 months (95% CI 14.1-21.8 months) versus 20.5 months (95% CI 15.0-25.4 months), respectively (HR 0.75; 95% CI 0.49-1.22; P = 0.16). CONCLUSIONS: Regorafenib-personalized schedules are commonly adopted in daily clinical practice of high-volume GIST expert centers and correlate with significant improvement of therapeutic outcomes. Therefore, regorafenib treatment optimization in patients with GIST may represent the best strategy to maximize long-term therapy.

Dental identification of unknown bodies through antemortem data taken by non-dental X-rays. Case reports.

The dental radiographic comparison is one of the most reliable and scientifically accepted methods for body identification (ID). The heterogeneity between AM (ante mortem) and PM (postmortem) x-rays images continues to stand as an issue for the forensic odontologist. Casual dental findings on X-rays for investigation of other structures than teeth or maxillaries, could eventually be a relevant source of dental data for the ID especially when AM dental files or X-rays are lacking. Two cases are reported in which the body ID was achieved through the comparison of PM dental X-rays with dental images obtained by radiographies of other structures (e.g. X-rays of the skull or cervical spine). These cases highlight that these occasional dental findings might provide sufficient evidence for a body identification. In the collection of AM data of missing people, the collection of all available records and radiographies of the head, neck and chest should be carefully reviewed by forensic odontologists, seeking for any available dental data.

Intrahepatic cholangiocarcinoma development in a patient with a novel BAP1 germline mutation and low exposure to asbestos.

BRCA1 associated protein-1 (BAP1) germline mutations define a novel hereditary cancer syndrome, namely BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by an increased susceptibility to develop different cancer types, including mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and basal cell and squamous cell carcinoma. Currently, the role of BAP1 germline mutations in intrahepatic cholangiocarcinoma (iCCA) pathogenesis is less known. Here we report the first clinical case of a female patient who developed an iCCA when she was 47-years-old and was found to carry a novel germline mutation at a splicing site of exon 4 in BAP1 gene (NM_004656.4: c.255_255+6del). An accurate anamnesis revealed the absence of risk factors linked to iCCA development, except for a low occupational exposure to asbestos. In tumor tissue, BAP1 sequencing, multiplex ligation-dependent probe amplification and immunoistochemistry showed the loss of heterozygosity and lack of nuclear expression, suggesting that BAP1 wild-type allele and functional protein were lost in cancer cells, in line with the classical two-hit model of tumor suppressor genes. Further studies are needed to confirm whether iCCA may be included into BAP1-TPDS cancer phenotypes and whether minimal asbestos exposure may facilitate the development of this malignancy in individuals carrying BAP1 germline mutations.

Activated macrophages are the main inflammatory cell in COVID-19 interstitial pneumonia infiltrates. Is it possible to show their metabolic activity and thus the grade of inflammatory burden with 18F-Fluorocholine PET/CT?

The recent outbreak of Covid-19 has represented a major challenge for the countries affected by the disease, not only in terms of loss of human life, economic downturn, and constraint on individual freedom, but also for the great pressure on the national health systems and hospitals. The 380 kDa virus has been a perfect storm, especially for those national health systems used to working with limited resources and high intensity rhythms, such as Italy. For the first time in the new century, a virtually unknown fast-spreading disease has caused a public health emergency thus forcing most countries to deal with an insurmountable logistic gap. Hence, every branch of Medicine, even though not directly involved in the treatment, has been called upon to provide its contribution to resolve the crisis. It is now becoming more apparent that Covid-19 is not solely a lung disease, but a complex systemic disease involving several organs and systems. This is due to an abnormal inflammatory response which eventually leads to multisystemic coagulopathy which mainly, but not uniquely, targets the lungs. Although the pathophysiology of this syndrome is still not fully understood, macrophages and their immune complex system seem to play a key role. It is not yet clear why some patients develop the violent immune response which results in pneumonitis while others do not. There are clues indicating that the systemic hyper-inflammation defined as macrophage activation syndrome (MAS), or cytokine storm, requires an increase in choline consumption to synthesize phosphatidylcholine and stimulate phagocytosis, organelle biogenesis, secretory functions, and endocytosis. 18F-Fluorocholine is a synthetic analog of the naturally occurring choline normally used for PET/CT imaging of prostate cancer patients. 18F-Fluorocholine could image and quantify the macrophage activity in pulmonary interstitial infiltrates of Covid-19 pneumonia. If the hypothesis is confirmed experimentally, 18F-Fluorocholine PET/CT could be used to in vivo image and quantify the degree of lung inflammation and potentially stratify the gravity of this disease.

Paroxysmal eruptions tracked by variations of helium isotopes: inferences from Piton de la Fournaise (La Réunion island).

Helium (He) with its isotopes (3He, 4He) is a key tracer enabling the Earth's mantle and dynamics to be characterized. Enrichment in primordial helium (3He) has been detected in volcanic gases of numerous magmatic systems in different geodynamic settings. Despite past use to monitor volcano-tectonic unrest, temporal 3He/4He variability in volcanic emissions is still poorly constrained. Here, we investigate noble gas chemistry of Piton de la Fournaise hotspot volcano, where temporal fluctuations of 3He/4He in response to the eruptive activity have never been studied. We compare the 3He/4He signature of volcanic gases and fluid inclusions and we highlight analogous evolution of the 3He/4He signature in both during the last decades of eruptive activity (1990-2017), even during the same eruption. We show that the maximum enrichment in 3He is found in magmatic fluids that fed the most voluminous eruptions which culminated in caldera collapse events. We argue that this enrichment in 3He mostly reflects a greater contribution of magmatic fluids from a primitive component of the mantle plume. These results emphasize that He isotopes may provide warnings of increases in deep magmatic contributions that potentially herald paroxysmal eruptions, as documented here at Piton de la Fournaise (2007) and also at Kilauea (2018).

Constructed wetlands for combined sewer overflow treatment: A state-of-the-art review.

Combined sewer overflows (CSOs) are a major source of surface water pollution and degradation. This is particularly visible where sewage collection with combined sewer and centralized treatment are well established, such as in Europe and North America: an overwhelming number of surface water bodies are in insufficient status of ecology, hydrology and physico-chemical parameters. Therefore, several countries have started implementing constructed wetlands (CWs) as mainstream on-spot treatment. This paper summarizes the main design approaches that can be adopted. We identified eight different schemes for the implementation of CSO-CWs, based on our international experience and documented by a literature analysis. The performance review includes conventional water quality parameters, as well as pathogen and emergent contaminant removal. Furthermore, modelling tools for advanced design and for understanding a wide applicability of these green infrastructures are presented. This paper also provides a review on other side benefits offered by the adoption of Nature-Based Solutions for CSO treatment, such as ecosystem services, and the most common issues related to their operation and maintenance. Our analysis has produced a list of key factors for design and operation, all derived from full-scale installations in operation up to more than ten years.

Ozone therapy in veterinary medicine: A review.

Ozone (O3) is a triatomic form of oxygen. As O3 rapidly dissociates into water and releases a reactive form of oxygen that may oxidize cells, the gas mixture of O3/O2 is used in medicine. ATP is widely available for cellular activity. O3 can be administered via the systemic and local routes. Although O3 is known as one of the most powerful oxidants, it also promotes antioxidant enzymes. Additionally, it stimulates some of the cells of the immune system and inactivates pathogens, including bacteria, fungi, yeasts, protozoa, and viruses. Owing to these activities, O3 is used to improve several diseases, both in human and in veterinary medicine. Considering the wide scope of O3 application, the aim of this review was to reiterate the mechanisms of action of O3 and its utilization in different mammalian species (bovine, ovine-caprine, equine, canine, porcine).

Ganglio pélvico voluminoso que imita una infección protésica de cadera en gammagrafía con leucocitos marcados con 99mTc-HMPAO / Prominent pelvic lymph node mimicking a prosthetic hip infection on 99mTc-HMPAO labeled white blood cell scintigraphy

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