Gruppo Italiano per lo Studio dei Carcinomi dell’Apparato Digerente

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Abstract Climate change is profoundly altering forest phenology and productivity across Europe, with particularly strong impacts in Mediterranean regions characterized by high climatic heterogeneity. Understanding how climatic and site-specific drivers regulate the start, end, and length of the growing season, and how these phenological shifts translate into productivity responses, remains a key challenge for predicting forest carbon dynamics. In this study, we investigate phenological timing and total seasonal productivity across multiple Italian forest species spanning Mediterranean, temperate, and mountain environments, leveraging the new High-Resolution Vegetation Productivity and Phenology product from the Copernicus Land Monitoring Service, machine learning (random forests) modeling, and explainable artificial intelligence analysis (SHAP). Our results confirm a general lengthening of the growing season driven mainly by chilling accumulation and spring temperatures. Warmer conditions advance the start of the season by 1–10 days across species, while the combined effects of temperature, radiation, and moisture can extend the growing season by up to 20–30 days. End-of-season dynamics and season length are more strongly controlled by light and water availability than by temperature alone. In several Mediterranean species, the end of the season can advance by up to 40 days due to summer drought, high vapor pressure deficit, and site exposure. Mediterranean species often show compensatory shifts between season onset and senescence, maintaining a relatively stable length of the season, whereas mountain species exhibit a tighter coupling between delayed onset and shortened season length. Phenological shifts are frequently decoupled from productivity, which is mainly regulated by energy and water availability, highlighting species- and site-specific responses to climate change. The findings of this study highlight the substantial advantage of remote sensing data, coupled with machine learning approaches, for advancing the understanding of forest phenology and productivity across broad spatial and climatic gradients.

Mucus Fishing Syndrome (MFS) is a chronic inflammatory condition of the ocular surface characterized by repeated mechanical removal of mucus strands, leading to a cycle of irritation and excess mucus production. MFS is often associated with dry eye disease, meibomian gland dysfunction, blepharitis, and allergic conjunctivitis. Patients typically present with conjunctival hyperemia, irritation, and mucus accumulation. We describe two clinical cases of MFS in which low-level light therapy (LLLT) was used as part of a multimodal management approach. The first case involved a 32-year-old woman with a 2-year history of persistent symptoms despite previous treatments. The second case was a 50-year-old woman with severe discomfort and chronic mucus secretion unresponsive to tear substitutes alone. Both patients underwent conservative therapy including topical corticosteroids, acetylcysteine 5%, eyelid hygiene, and adjunctive LLLT (4 sessions in case #1 and 5 in case #2). MFS remains a challenging ocular surface condition requiring combined management of inflammation, mucin hypersecretion, and behavioral factors. In the cases presented, LLLT was incorporated as an adjunctive intervention within a broader therapeutic plan. Although improvement was observed, the contribution of LLLT cannot be determined based on these findings alone and further studies are needed to clarify its potential role in MFS management.

PurposeTo compare the efficacy and safety of topical insulin and amniotic membrane extract eye drops (AMEED) in promoting healing of corneal persistent epithelial defects (PEDs) refractory to conventional therapy.Patients and MethodsThis retrospective comparative study included 27 eyes of 24 patients (mean age 61.0 ± 16.6 years) with PEDs treated with either topical insulin (1 IU/mL) or AMEED four times daily. Clinical outcomes included complete epithelial closure, rate of epithelialization, change in best-corrected visual acuity (BCVA), and occurrence of adverse events.ResultsOf 27 eyes, 18 received topical insulin and 9 received AMEED. The mean interval from diagnosis to treatment initiation was 93.4 ± 111.7 days in the AMEED group and 72.5 ± 56.1 days in the insulin group. Complete healing occurred in all eyes (100%) in the insulin group versus 44.4% in the AMEED group. The daily reduction in epithelial defect area during the first two weeks was significantly greater with insulin (P = 0.04). At final follow-up, BCVA improved significantly only in the insulin group (P = 0.006). No adverse reactions were observed in either group; one AMEED-treated eye required amniotic membrane transplantation.ConclusionTopical insulin and AMEED are both safe and effective for refractory PEDs, but insulin showed superior epithelial healing and visual recovery. Given its availability, low cost, and favorable safety profile, topical insulin may represent a practical alternative in the management of persistent epithelial defects.

The retinal pigment epithelium (RPE) is essential for maintaining retinal integrity, and its dysfunction underlies several progressive ocular diseases, including age-related macular degeneration, choroidal neovascularization (CNV), inherited retinal disorders (IRDs), and proliferative vitreoretinopathy (PVR). Although current therapies have improved disease management, they mainly target secondary pathological mechanisms and do not directly preserve or restore RPE function. Moreover, the delivery of therapeutic molecules or genes to the RPE remains a major challenge due to the presence of multiple ocular barriers and the need for sustained, localized action. Nanomedicine offers innovative solutions to these limitations by enabling precise, controlled, and cell-specific delivery of drugs and genetic materials. Engineered nanocarriers can be optimized to traverse ocular barriers, enhance bioavailability, and modulate the retinal microenvironment. This review summarizes recent advances in nanoscale delivery systems for RPE-targeted therapies, focusing on design principles, targeting strategies, and therapeutic applications, and discusses the translational challenges that must be addressed to bring nanotechnology-based treatments closer to clinical application.

Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural changes such as proptosis and diplopia, and are associated with substantial adverse effects. This review aims to synthesize recent developments in understandings of TED pathogenesis and to critically evaluate emerging therapeutic strategies. Methods: A systematic literature review was conducted using MEDLINE, Embase, and international clinical trial registries focusing on pivotal clinical trials and investigational therapies targeting core molecular pathways involved in TED. Results: Current evidence suggests that TED pathogenesis is primarily driven by the autoimmune activation of orbital fibroblasts (OFs) through thyrotropin receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R) signaling. Teprotumumab, a monoclonal IGF-1R inhibitor and the first therapy approved by the U.S. Food and Drug Administration for TED, has demonstrated substantial clinical benefit, including improvements in proptosis, diplopia, and quality of life. However, concerns remain regarding relapse rates and treatment-associated adverse events, particularly hearing impairment. Investigational therapies, including next-generation IGF-1R inhibitors, small-molecule antagonists, TSH-R inhibitors, neonatal Fc receptor (FcRn) blockers, cytokine-targeting agents, and gene-based interventions, are under development. These novel approaches aim to address both inflammatory and fibrotic components of TED. Conclusions: Teprotumumab has changed TED management but sustained control and toxicity reduction remain challenges. Future therapies should focus on targeted, mechanism-based, personalized approaches to improve long-term outcomes and patient quality of life.

To investigate the contribution of nasal surgery to multilevel OSA surgical success outcome. Systematic review of MEDLINE, Google Scholar, Cochrane Library and Evidence Based Medicine Reviews to identify publications relevant to OSA, nasal resistance, pharyngeal volume/space, nasal surgery, multilevel surgery and its outcomes. All relevant studies published between January 2000 to December 2024 were included. Twelve studies were included in this systematic review with 11 articles illustrating that nasal surgery was pivotal, and improved outcomes in multilevel OSA surgery, whilst nasal surgery alone for OSA did not significantly affect polysomnographic results. Five articles utilizing CBCT, 3D measurements of nasal and pharyngeal airway area/volume, computational fluid dynamics and nasal resistance demonstrated that reducing nasal resistance with nasal surgery increased the pharyngeal airway space and volume; whilst 6 articles established through clinical case studies that multilevel OSA surgery combined with nasal surgery yielded better AHI, LSAT and ESS outcomes than multilevel surgery without nasal surgery. The landmark article that reviewed 24 years of nasal surgery alone for OSA treatment, showed poor outcomes and minimal AHI change with nasal surgery alone. As the upper airway is a continuous air conduit, reducing nasal resistance would reduce pharyngeal pressures leading to improvement of outcome parameters. Hence, including nose surgery in multilevel surgery improves surgical success.

Background/Objectives: The management of ocular tumors often necessitates surgery, either alone or in combination with radiotherapy, chemotherapy, or other modalities. While crucial for tumor control, these treatments can significantly impact the ocular surface, leading to both acute and chronic complications. This review examines iatrogenic ocular surface diseases resulting from oncologic interventions, emphasizing their pathophysiology, diagnostic challenges, and management strategies. Methods: A literature review was conducted to identify studies on iatrogenic ocular surface complications associated with ocular tumor treatments. Results: Ocular surface complications include direct damage from surgical manipulation, leading to corneal opacities and persistent epithelial defects, as well as dry eye disease secondary to postoperative chemosis. These disruptions may progress to more severe conditions such as keratopathy, corneal ulcers, limbal stem cell deficiency, and stromal scarring, further impairing visual function. Structural alterations contribute to eyelid malpositions-including ectropion, entropion, round eye, and lagophthalmos-which exacerbate exposure-related damage and ocular surface instability. In cases of uveal melanomas, the exposure of episcleral brachytherapy plaques can induce chronic conjunctival irritation, promoting adhesion formation and symblepharon. Surgical interventions disrupt ocular surface homeostasis, while radiotherapy and chemotherapy exacerbate these effects through cytotoxic and inflammatory mechanisms. Conclusions: Preventing and managing iatrogenic ocular surface complications require a multidisciplinary approach involving early diagnosis, personalized treatment strategies, and targeted postoperative care. Comprehensive pre- and postoperative planning is essential to optimize both visual function and long-term ocular surface integrity, ultimately ensuring a balance between oncologic control with functional and aesthetic preservation.