Francesca Cascone

Liquid biopsy, the analysis of tumor-derived material in blood, saliva, and other body fluids, is increasingly explored for the diagnosis, surveillance, and molecular characterization of head and neck squamous cell carcinoma (HNSCC). Its performance, however, is not uniform across the disease, and the reason is fundamentally molecular. human papillomavirus (HPV)-positive oropharyngeal cancers carry viral oncogenes that are absent from the host genome and therefore provide a near ideal, tumor specific circulating marker, whereas HPV-negative tumors are driven by a heterogeneous somatic landscape that offers no single universal target. In this narrative review, we adopt a molecular perspective. We first examine the biological origin of circulating tumor DNA and of the other analytes that liquid biopsy can interrogate including circulating tumor HPV DNA, viral transcripts, microRNAs, extracellular vesicles, and methylation signatures. We then consider how analytical platforms, from droplet digital PCR to next generation and ultrasensitive whole-genome sequencing, translate these molecules into measurements. Only afterward do we discuss the clinical questions, organized by clinical objective rather than by individual study: diagnosis and early detection, prognosis and risk stratification, treatment response monitoring, minimal residual disease and surveillance, and biomarker guided de-escalation in HPV-positive disease. Twelve registered clinical trials, involving approximately 1183 patients, are presented as illustrations of these questions. We close on the biological and technical gaps that still separate promising signals from clinical practice, and on the multi analyte and dynamic strategies most likely to bridge them. At present, liquid biopsy should be regarded as a complementary tool rather than as a replacement for established clinicopathological assessment.

Long COVID is defined as “the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanations”, as reported by the World Health Organization. A growing number of people are dealing with a variety of lingering symptoms even after recovering from an acute infection. These can include fatigue, muscle pain, shortness of breath, headaches, cognitive issues, neurodegenerative symptoms, anxiety, depression, and a feeling of hopelessness, and therapeutic options for long COVID are investigated. The potential of hyperbaric oxygen therapy (HBOT) to improve chronic fatigue, cognitive impairments, and neurological disorders has been established; therefore, the use of HBOT to treat long COVID has also been studied. The aim of this literature search is to analyze the state of the art of a potential role of HBOT to improve chronic fatigue, cognitive impairments and neurological disorders. A literature analysis was performed, focusing on the clinical efficacy of HBOT for treating long COVID symptoms. The results from January 2021 to October 2025, using a standard registry database, showed 21 studies, including one case report, ten randomized controlled trial, eight systematic reviews and three studies regarding the molecular mechanism and markers changing after HBOT. They suggested that HBOT can improve quality of life, fatigue, cognition, neuropsychiatric symptoms and cardiopulmonary functions. HBOT is a safe treatment and has shown some benefits for long COVID symptoms. To precisely define indications, protocols, and post-treatment evaluations, we need to conduct more in-depth, large-scale studies.

Ocular flutter is an uncommon ophthalmic finding that may indicate paraneoplastic phenomena, and it is clinically characterized by intermittent bursts of conjugate, horizontal saccades without an intersaccadic interval. Ocular flutter must be differentiated from opsoclonus, which, although also characteristic of certain paraneoplastic syndromes, is instead defined by multidirectional saccades on both the horizontal and vertical planes. This report describes a very rare presentation of anti-Ri syndrome in a patient with an undiagnosed breast cancer, presenting with ocular flutter, dizziness, blurred vision, photophobia, and vomiting. Comprehensive evaluations, including contrast-enhanced brain Magnetic Resonance Imaging (MRI), brain Computed Tomography (CT) scan, ophthalmological assessment, viral serology, complete blood count and thyroid, renal coagulation, hepatic function assessments, vitamin D and B12 levels, were all normal. Upon excluding other potential etiologies for the neurological symptoms, a paraneoplastic origin was considered. Serological tests confirmed the presence of anti-Ri onconeural antibodies, and a whole-body CT scan identified nodules in the right breast. Despite surgical excision of the primary tumor and subsequent medical therapy, there was no improvement in the neurological symptoms. Follow-up evaluations at 2 months, 6 months, 1 year and 2 years revealed persistent vestibular and neurological symptoms, with serum tests remaining positive for anti-Ri antibodies and no clinical or radiological evidence of neoplastic recurrence.

Pharyngocutaneous fistulas (PCF) are a common postoperative complication following head and neck surgery, particularly after total laryngectomy. These types of fistulas represent a challenge for both patients and clinicians due to their persistence and resistance to conventional healing methods. Hyperbaric Oxygen Therapy (HBOT) has been proposed as an adjunctive treatment to enhance healing and closure of PCF. While many studies report positive outcomes, the results are not universally consistent. This comprehensive review aimed to examine the clinical evidence supporting the efficacy of HBOT in the management of pharyngocutaneous fistulas, focusing on fistula closure rates, infection control, and overall healing improvement. All publications without the restriction of time and published in the English language were included. Searches were performed in the PubMed, MEDLINE, Scopus, and Embase databases. Ten articles were included in this review. The evaluation of our clinical experience with this method of treating PCF showed results comparable to those found in the literature and analyzed among the studies reviewed. Several studies indicate that HBOT promotes fistula closure, reduces healing time, and enhances the local immune response, but further investigation is required to optimize protocols and patients’ selections.

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease with multifactorial etiopathogenesis. This study investigated the recurrence rate and risk factors predicting recurrence in patients subjected to Functional Endoscopic Sinus Surgery (FESS) for CRSwNP. Methods: Patients affected by CRSwNP who underwent FESS between January 2015 and March 2020 were enrolled. The recurrence rate and the influence of risk factors were assessed. Results: A total of 154 patients were included, 100 males and 54 females, aged 14–82 years (mean age 51.96 ± 16.27; median 52 years). Of 154 patients, 28 presented CRSwNP recurrence in a follow-up period ranging from 6 months to 69 months, with a recurrence rate of 18.2%. The recurrence rate was higher in patients aged between 31 and 50 years and between 51 and 70 years at the time of surgery than in those aged between 14 and 30 years and over 70 years. Furthermore, most patients with recurrence were men (61%), while 39% were women. A higher recurrence rate was observed between non-smokers (50%) and ex-smokers (36%), while only 14% declared themselves habitual smokers. Only four subjects (14%) had a positive family history of CRSwNP. Conclusion: To date, no specific biomarkers have been identified in order to determine the appropriate therapy for the patients affected by CRSwNP. Based on our results, we suggest that it is necessary for an accurate assessment of the CRSwNP patients to identify which phenotype/endotype each subject manifests based on medical history, endoscopy, computed tomography, and a laboratory evaluation.

Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent hypoxia (IH) during sleep due to recurrent upper airway obstruction. The derived oxidative stress (OS) leads to complications that do not only concern the sleep-wake rhythm but also systemic dysfunctions. The aim of this narrative literature review is to investigate molecular alterations, diagnostic markers, and potential medical therapies for OSAS. We analyzed the literature and synthesized the evidence collected. IH increases oxygen free radicals (ROS) and reduces antioxidant capacities. OS and metabolic alterations lead OSAS patients to undergo endothelial dysfunction, osteoporosis, systemic inflammation, increased cardiovascular risk, pulmonary remodeling, and neurological alterations. We treated molecular alterations known to date as useful for understanding the pathogenetic mechanisms and for their potential application as diagnostic markers. The most promising pharmacological therapies are those based on N-acetylcysteine (NAC), Vitamin C, Leptin, Dronabinol, or Atomoxetine + Oxybutynin, but all require further experimentation. CPAP remains the approved therapy capable of reversing most of the known molecular alterations; future drugs may be useful in treating the remaining dysfunctions.