Background: Head and neck cancers, and particularly, oral cancers have a complex pathogenesis that includes genetic mutations and epigenetic alterations which interfere with cellular signaling and can trigger tumor development. The purpose of this study was to reveal whether low-frequency hotspot mutations may be detected in a study lot with histopathological evidence of squamous cell carcinoma (SCC) of the oral mucosa and skin of the head and neck. Methods: Tumor biopsies from treatment- naïve patients were tested for BRAF V600, NRAS G12/G13, NRAS Q61, KRAS Q61 mutations, and EGFR exon 19 deletions (Ex19Del) using droplet digital PCR (ddPCR). The tumors were also analyzed for EGFR T790M mutations by RT-PCR, using a CE-IVD validated kit, with a limit of detection of 0.05%. Results: None of the examined cases exhibited NRAS G12/G13, NRAS Q61, KRAS Q61, BRAF V600, or EGFR T790M mutations, indicating that these alterations are rare events in SCC pathogenesis. Interestingly, among the 12 specimens tested by ddPCR for EGFR Ex19Del, an HPV-negative cSCC tumor occurring in the parotid region tested positive for this drug-sensitizing mutation, offering unexplored therapeutic perspectives to the patient from whom it was collected. Conclusions: Our study highlights the important clinical implications of detecting low-frequency hotspot mutations in tumor biopsies by ddPCR. We believe that the ddPCR-assisted analysis of these mutations in larger SCC cohorts may provide us with mechanistic insights regarding their role in SCC pathogenesis and guide the development of novel therapeutic strategies for this problematic disease.
Synovial proliferation is a common intraoperative finding during total knee arthroplasty (TKA) and many studies have proposed synovectomy for the reduction of postoperative pain. We included 180 patients that were split into two groups, one which received a total synovectomy (TS) and the other with partial synovectomy (PS). We measured the amount of intra- and post-operative bleeding as well as perceived pain (using the Visual Analogue Scale) and knee function (using the Knee Society Knee Score) at 4 and 12 weeks. The blood loss during the surgical procedure was 367.77 ± 115.71 mL for TS, while the other group recorded 295.55 ± 106.17 mL (p < 0.05). Regarding postoperative bleeding, the TS group aspirated 533.77 ± 281.65 mL, which was significantly higher than the PS group (404.44 ± 211.55 mL, p < 0.05). No significant differences were recorded between the TS and PS groups regarding pain and knee function at 12 weeks. Total synovectomy demonstrated significantly higher blood loss and lower postoperative hemoglobin levels, even though knee function and pain level did not show improvements. We consider that the decision of performing synovectomy should rely on the clinical indication and, if conditions allow for it, a limited resection should be attempted.
Background: Pheochromocytomas (Pheo) are rare neuroendocrine tumors with a suggestive clinical picture, characterized by hypersecretion of catecholamines and other neuroendocrine biomarkers. Methods: The purpose of the study was to analyze the diagnostic features of Pheo and investigate the role played by different neuroendocrine and hormonal markers in diagnosing Pheo.The retrospective study involved a group of 69 patients diagnosed and treated with Pheo, who had both urinary and plasma catecholamines and neuroendocrine markers measured pre- and postoperatively. Results: After comparing pre- and postoperative hormonal parameters and neuroendocrine biomarker changes, numerous statistically significant findings were found. The analysis of the relationships between chromogranin A (CgA) levels, plasma and urine metanephrines, and normetanephrine and Pheo tumor size was included in the study. Additionally, we evaluated Cg A's diagnostic efficacy in comparison to plasma metanephrines, normetanephrine, and neuron-specific enolase (NSE) for Pheo. Conclusions: We obtained statistically significant data on pre- and postoperative differences for plasma and urinary catecholamines, CgA and NSE. Pheo tumor size is interdependent with serum levels of Cg A, plasma and urinary metanephrines, and normetanephrine. The best diagnostic power for Pheo was plasma normetanephrine, followed by plasma metanephrines and CgA.
Introduction. Management of moderate-severe psoriasis is challenging in the presence of severe systemic comorbidities, such as HIV infection, recent history of cancer, latent tuberculosis infection, or advanced liver disease. These patients are almost invariably excluded from randomized clinical trials, an aspect that limits the availability of standardized therapeutic options. Material and methods. This narrative review summarizes the current literature on immunomodulatory therapeutic strategies in patients with psoriasis and severe systemic comorbidities, integrating existing evidence in the literature with relevant clinical observations from real-world practice. Results. Available data suggest that therapeutic decisions should be individualized according to the type of comorbidities and severity of the disease. In well-controlled HIV infection, conservative strategies may be preferred. In patients with a history of cancer, systemic therapies may be used with caution and in interdisciplinary collaboration. In latent tuberculosis infection, prophylaxis is necessary, but isoniazid-induced hepatotoxicity is an important limitation. In liver disease, biological therapies may constitute a safer alternative to conventional systemic therapy. Conclusion. In this context, patients with psoriasis and severe associated systemic comorbidities require a personalized, multidisciplinary approach and close monitoring. Real-world data play an essential role in guiding therapeutic decisions in this patient population.
