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Several dermal substitutes are available on the market, but there is no precise indication that helps surgeons choose the proper one. Few studies have tried to compare different xenogeneic bioengineered products, but no objective bio-parametric comparison has been made yet. Fifteen patients who underwent skin reconstruction with Integra® or Pelnac® were retrospectively evaluated. After at least 12 months of follow-up, an objective and quantitative assessment of several skin biophysical properties, such as color, texture, elasticity, hydration, glossiness and trans-epidermal water loss, were measured with non-invasive skin measurement devices. The grafted skin showed a reduction of the superficial hydration level and a tendency to lower values of trans-epidermal water loss with both dermal substitutes. Melanic and hemoglobin pigmentation were higher in comparison to the donor site in both groups, while a melanic pigmentation increase versus the surrounding skin was seen just with Integra®. Finally, the skin was found to be more elastic when reconstructed with Integra®. The skin barrier appeared to be intact in both groups. Hence, these substitutes are valuable means of skin regeneration. Integra® seems to be more advantageous for reconstructing areas that need more skin flexibility.

Background Conventional radiotherapy (CONV-RT) is widely used for cancer treatment, but its efficacy is limited by toxicity to surrounding healthy tissues. Ultra-high dose rate radiotherapy (FLASH-RT) has emerged as a promising approach, maintaining tumor control while sparing normal tissues. Melanoma is highly radioresistant, and deep-seated lesions expose skin and muscle to radiation, causing long-term fibrosis, stiffness, and loss of elasticity. The aim of this study is to compare the efficacy and collateral effects of CONV-RT and FLASH-RT, using melanoma as a benchmark for tumor response and skin–muscle as a model for normal tissue toxicity, and to investigate the underlying molecular and systemic mechanisms. Methods A novel linear accelerator (LINAC) delivering low-energy electrons at ultra-high dose rate via a triode gun with precise tissue targeting and dose delivery was used. CONV-RT and FLASH-RT were administered to a syngeneic melanoma mouse model. Tumor growth, skin and muscle integrity, transcriptional changes, and systemic homeostasis were analyzed in tumor-bearing and naïve mice. Results Both modalities achieved comparable tumor suppression. CONV-RT induced persistent skin damage, dermal fibrosis, muscle dysfunction, and systemic inflammatory–metabolic alterations, whereas FLASH-RT largely preserved tissue architecture and systemic balance. Bulk RNA sequencing revealed minimal transcriptional disruption after FLASH-RT, while CONV-RT triggered thousands of differentially expressed genes, including pathways related to fibrosis, inflammation, cell death in skin, and muscle remodeling, function, and the unfolded protein response. Histological and ultrastructural analyses confirmed reduced immune infiltration and preserved tissue structure following FLASH-RT. Conclusions FLASH-RT provides effective tumor control while largely preserving normal tissues. CONV-RT and FLASH-RT elicit substantially different biological responses, suggesting the involvement of upstream modulators that vary depending on the dose rate. Graphical Abstract

Background Both macroscopic and histological lesions are frequently detected at upper endoscopy in elderly patients. We assessed the prevalence of main endoscopic and histological alterations in elderly (> 65 years old) patients. Methods In this study, clinical, endoscopic and histological features of patients referred for upper endoscopy in clinical practice were retrieved. Both univariate and multivariate analyses were executed. Comparisons with previous data were performed. Results A total of 1336 underwent upper endoscopy in the 28 participating centres. At endoscopy, at least one macroscopic lesion was present in overall 420 (31.4%) patients. Erosive gastritis (13.3%) and erosive oesophagitis (9.8%) were the most prevalent lesions, whilst Barrett’s oesophagus, gastric ulcer, duodenal ulcer and erosive duodenitis were observed in 1.8%, 2%, 1.4% and 3.1% patients, respectively. Nine (0.6%) cases of oesophageal, 25 (1.8%) gastric and 2 (0.1%) duodenal neoplasia were detected. At histology, Helicobacter pylori infection was diagnosed in 99 (15.9%) patients, and extensive precancerous lesions on gastric mucosa were detected in 80 (14.5%) patients. Endoscopic lesions were more frequent in males, at first endoscopy and in those with alarm symptoms and lower during PPI therapy. At multivariate analysis, PPI therapy significantly reduced the probability of finding endoscopic lesions (OR: 0.68, 95% CI: 0.46–0.99; P  = 0.04), whilst neoplastic lesions were associated with presence of alarm symptoms (OR: 1.5, 95% CI: 1.1–2.1; P  = 0.005). Conclusions We found that the frequency of erosive and neoplastic lesions remained high in elderly patients, whilst the prevalence of both H. pylori infection and peptic ulcer was decreased.

Background Remdesivir is widely used for treatment of SARS-CoV-2 pneumonia. The aim of this study was to evaluate the characteristics of patients with moderate-to-severe COVID-19 treated with remdesivir, and their outcomes during hospitalization. Methods This retrospective observational multicenter study included consecutive patients, hospitalized for moderate-to-severe COVID-19 (September 2020—September 2021), who were treated with remdesivir. Results One thousand four patients were enrolled, all with onset of symptoms occurring less than 10 days before starting remdesivir; 17% of patients had 4 or more concomitant diseases. Remdesivir was well tolerated, adverse drug reactions (ADRs) being reported in 2.3% of patients. In-hospital death occurred in 80 patients (8.0%). The median timing of the first remdesivir dose was 5 days after symptom onset. The following endpoints did not differ according to the time span from the onset of symptoms to the first dose: length of hospitalization, in-hospital death, composite outcome (in-hospital death and/or endotracheal intubation). Advanced age, number of comorbidities ≥ 4, and severity of respiratory failure at admission were associated with poor in-hospital outcomes. Conclusion In a real-world setting, remdesivir proved to be a safe and well-tolerated treatment for moderate-to-severe COVID-19. In patients receiving remdesivir less than 3 or 5 days from the onset of SARS-CoV-2 symptoms, mortality and the need for mechanical ventilation did not differ from the rest of the sample.

Remnants of early films often have a story to tell. As material artifacts, these film fragments are central to cinema history, perhaps more than ever in our digital age of easy copying and sharing. If a digital copy is previewed before preservation or is shared with a researcher outside the purview of a film archive, knowledge about how the artifact was collected, circulated, and repurposed threatens to become obscured. When the question of origin is overlooked, the story can be lost. Concerned contributors in Provenance and Early Cinema challenge scholars digging through film archives to ask, \"How did these moving images get here for me to see them?\" This volume, which features the conference proceedings from Domitor, the International Society for the Study of Early Cinema, 2018, questions preservation, attribution, and patterns of reuse in order to explore singular artifacts with long and circuitous lives.

Radiotherapy (RT) is a cornerstone treatment for nearly 50% of cancer patients, but its curative potential and safe dosing are constrained by cumulative toxicity to surrounding healthy tissues. Delivering RT at ultra-high dose rates (FLASH-RT) represents a transformative strategy, as it appears to maintain tumor control, while sparing normal tissue. Melanoma is among the most radioresistant tumors, and skin and muscle are invariably exposed during RT, also in case of deep seated tumors. Here, we compared electron FLASH-RT and conventional RT (CONV-RT) in melanoma-bearing and naïve mice assessing tumor control, tissue integrity, and systemic homeostasis over the medium to long term. Both modalities achieved comparable tumor suppression. However, CONV-RT induced persistent skin damage, dermal fibrosis, muscle dysfunction and systemic inflammatory-metabolic alterations, while FLASH-RT largely spared normal tissue and systemic balance. Bulk RNA sequencing revealed striking differences: FLASH induced minimal transcriptional disruption in skin and muscle, whereas CONV-RT triggered thousands of differentially expressed genes, including massive activation of fibrosis, inflammation, cell death-related pathways in skin, and broad dysregulation of genes linked to muscle function, remodeling and the unfolded protein response. Histological and ultrastructural analyses corroborated the findings, showing reduced immune infiltration in the skin and preserved tissue architecture both in skin and muscle following FLASH. In conclusion our study not only confirms the protective nature of FLASH but also provides novel mechanistic insights into the cascade linking local injury to systemic dysfunction under CONV-RT, reinforcing the translational potential of FLASH to expand the therapeutic window of radiotherapy. Comparative analysis of FLASH and conventional radiotherapy in a murine model of melanoma and naïve mice - Therapeutical efficacy, local and systemic effects.