The accuracy of burn depth diagnosis: Clinical assessment before and after enzymatic debridement

Abstract Introduction The most common technique used to determine burn depth is clinical assessment by experienced burn surgeons, although this has been shown to be reliable in only 60–75% of the cases. Overestimation of burn depth may result in needles surgery, while burn depth underestimation can led to an increased length of stay in the hospital, risk of contracture and hypertrophic scar formation. The aim of this study was to assess the clinical evaluation of burn depth before and after enzymatic debridement with Nexobrid®. Methods The study model was retrospective. 69 patient records were collected at our burn units, from Jan 2018 to Jan 2019. Each target wound was directly assessed by a single expert physician before and after enzymatic debridement. It was investigated whether the expert, by single wound, would have indicated the need for skin grafts before treatment with Nexobrid® and after treatment. Results Prior to treatment with Nexobrid®, the expert physician assessed that a graft was necessary for 47/69 patients (68.1%). Following debridement, the same expert deemed that the patients needing a graft were 19/69 (27.5%); analysing K-agreement, a 40.6% discrepancy between the pre and post-treatment opinion with Nexobrid® was observed. Discussion The use of Nexobrid® enzymatic debridement can positively affect burn depth clinical assessment, increasing its specificity and sensitivity, without any need for delay. This can lead to a significant change in clinical practice, minimizing the use of surgery, therefore increasing quality and precision of the reconstructive phase

Preventing the acute skin side effects in patients treated with radiotherapy for breast cancer: the use of corneometry in order to evaluate the protective effect of moisturizing creams

BACKGROUND AND PURPOSE: The purpose of this study was to add, to the objective evaluation, an instrumental assessment of the skin damage induced by radiation therapy. MATERIALS AND METHODS: A group of 100 patients affected by breast cancer was recruited in the study over one year. Patients were divided into five groups of 20 patients. For each group it was prescribed a different topical treatment. The following products were used: Betaglucan, sodium hyaluronate (Neoviderm®), Vitis vinifera A. s-I-M.t-O.dij (Ixoderm®), Alga Atlantica plus Ethylbisiminomethylguaicolo and Manganese Cloruro (Radioskin1®) and Metal Esculetina plus Ginko Biloba and Aloe vera (Radioskin 2®); Natural triglycerides-fitosterols (Xderit®); Selectiose plus thermal water of Avene (Trixera+®). All hydrating creams were applied twice a day starting 15 days before and one month after treatment with radiations. Before and during treatment patients underwent weekly skin assessments and corneometry to evaluate the symptoms related to skin toxicity and state of hydration. Evaluation of acute cutaneous toxicity was defined according to the RTOG scale. RESULTS: All patients completed radiotherapy; 72% of patients presented a G1 cutaneous toxicity, 18% developed a G2 cutaneous toxicity, 10% developed a G3 toxicity, no one presented G4 toxicity. The corneometry study confirmed the protective role of effective creams used in radiation therapy of breast cancer and showed its usefulness to identify radiation-induced dermatitis in a very early stage. CONCLUSIONS: The preventive use of topic products reduces the incidence of skin side effects in patients treated with radiotherapy for breast cancer. An instrumental evaluation of skin hydration can help the radiation oncologist to use strategies that prevent the onset of toxicity of high degree. All moisturizing creams used in this study were equally valid in the treatment of skin damage induced by radiotherapy

Using auditory stimulation to enhance athletes’ strength: An experimental study in weightlifting

In the last fifteen years sport psychology researchers have developed different perceptual strategies based on auditory stimulation in order to improve athletes’ skills. Most of these strategies focused on providing athletes with the correct timing of action, in order to make this information available for motor production setting. However, it has also been demonstrated that some sounds can be a useful tool to modulate the physiological arousal in order to optimize sport performances. In our study we propose a protocol of intervention based on the stimulation with an auditory track whose intensity varies in correspondence with the physical effort of each phase of a bench press exercise. Eighteen participants performed three bench press lifts, both in experimental condition (with the auditory stimulus) and in control condition (without any stimulation). We measured the power exerted during the lifting. The results show that athletes can take advantage of the stimulus we provided, evidencing a higher average exertion of power in the experimental condition, compared to the control condition. Concluding, the results suggest that auditory perception can be a productive field of research in developing experimental strategies to improve athletes’ skills

Valproic Acid Synergizes With Cisplatin and Cetuximab in vitro and in vivo in Head and Neck Cancer by Targeting the Mechanisms of Resistance

Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a devastating malignancy with a poor prognosis. The combination of cisplatin (CDDP) plus cetuximab (CX) is one of the standard first-line treatments in this disease. However, this therapeutic regimen is often associated with high toxicity and resistance, suggesting that new combinatorial strategies are needed to improve its therapeutic index. In our study, we evaluated the antitumor effects of valproic acid (VPA), a well-known antiepileptic agent with histone deacetylase inhibitory activity, in combination with CDDP/CX doublet in head and neck squamous cell carcinoma (HNSCC) models. We demonstrated, in HNSCC cell lines, but not in normal human fibroblasts, that simultaneous exposure to equitoxic doses of VPA plus CDDP/CX resulted in a clear synergistic antiproliferative and pro-apoptotic effects. The synergistic antitumor effect was confirmed in four different 3D-self-assembled spheroid models, suggesting the ability of the combined approach to affect also the cancer stem cells compartment. Mechanistically, VPA enhanced DNA damage in combination treatment by reducing the mRNA expression of ERCC Excision Repair 1, a critical player in DNA repair, and by increasing CDDP intracellular concentration via upregulation at transcriptional level of CDDP influx channel copper transporter 1 and downregulation of the ATPAse ATP7B involved in CDDP-export. Valproic acid also induced a dose-dependent downregulation of epidermal growth factor receptor (EGFR) expression and of MAPK and AKT downstream signaling pathways and prevent CDDP- and/or CX-induced EGFR nuclear translocation, a well-known mechanism of resistance to chemotherapy. Indeed, VPA impaired the transcription of genes induced by non-canonical activity of nuclear EGFR, such as cyclin D1 and thymidylate synthase. Finally, we confirmed the synergistic antitumor effect also in vivo in both heterotopic and orthotopic models, demonstrating that the combined treatment completely blocked HNSCC xenograft tumors growth in nude mice. Overall, the introduction of a safe and generic drug such as VPA into the conventional treatment for R/M HNSCC represents an innovative and feasible antitumor strategy that warrants further clinical evaluation. A phase II clinical trial exploring the combination of VPA and CDDP/CX in R/M HNSCC patients is currently ongoing in our institute

Time of symptom onset and histologic findings in bladder pain syndrome/interstitial cystitis: new findings on useful correlations

The aim was to find out whether a correlation exists between denudation of urothelium and time of symptom onset in patients with bladder pain syndrome/interstitial cystitis (BPS/IC), and to search a correlation between impact of symptoms evaluated with ICSI-ICPI and the presence of comorbid conditions associated with BPS/IC. Ninety-seven consecutive patients underwent cystoscopy under general anesthesia to classify those cases suspected of being affected from BPS/IC. Three cold bladder biopsies were taken including detrusor muscle. Statistical analysis showed significant correlation between IC/BPS duration and the presence of Hunner's lesions (P<0.023). Hunner's lesion with cystoscopy and histological evidence of urothelial denudation with bladder biopsy appear to be items related to IC/BPS duration. Thus an early diagnosis allows to start an appropriate therapeutic approach and prevent a more severe evolution of this multifaceted painful syndrome. Our study shows a correlation between time of symptom onset and evidence of urothelial denudation and with detrusor mast cell count in the whole group of patients. IC/BPS duration seem to correlate with the presence of associated diseases

Urinary Excretion of Kidney Aquaporins as Possible Diagnostic Biomarker of Diabetic Nephropathy

Diabetic nephropathy (DN) is a microangiopathic complication of diabetes mellitus (DM) affecting one-third of diabetic patients. The large variability in the clinical presentation of renal involvement in patients with DM makes kidney biopsy a prerequisite for a correct diagnosis. However, renal biopsy is an invasive procedure associated with risk of major complications. Numerous studies aimed to identify a noninvasive biomarker of DN but, so far, none of these is considered to be sufficiently specific and sensitive. Water channel aquaporins (AQPs), expressed at the plasma membrane of epithelial tubular cells, are often dysregulated during DN. In this work, we analyzed the urine excretion of AQP5 and AQP2 (uAQP5 and uAQP2), via exosomes, in 35 diabetic patients: 12 normoalbuminuric with normal renal function (DM), 11 with proteinuric nondiabetic nephropathy (NDN), and 12 with histological diagnosis and classification of DN. ELISA and WB analysis independently showed that uAQP5 was significantly increased in DN patients. Interestingly, linear regression analysis showed a positive correlation between uAQP5 and the histological class of DN. The same analysis, focusing on uAQP2, showed comparable results. Taken together, these data suggest a possible use of AQP5 and AQP2 as novel noninvasive biomarkers to help in classifying the clinical stage of DN

Further Clarification of Pain Management Complexity in Radiotherapy: Insights from Modern Statistical Approaches

Background: The primary objective of this study was to assess the adequacy of analgesic care in radiotherapy (RT) patients, with a secondary objective to identify predictive variables associated with pain management adequacy using a modern statistical approach, integrating the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and the Classification and Regression Tree (CART) analysis. Methods: This observational, multicenter cohort study involved 1387 patients reporting pain or taking analgesic drugs from 13 RT departments in Italy. The Pain Management Index (PMI) served as the measure for pain control adequacy, with a PMI score &lt; 0 indicating suboptimal management. Patient demographics, clinical status, and treatment-related factors were examined to discern the predictors of pain management adequacy. Results: Among the analyzed cohort, 46.1% reported inadequately managed pain. Non-cancer pain origin, breast cancer diagnosis, higher ECOG Performance Status scores, younger patient age, early assessment phase, and curative treatment intent emerged as significant determinants of negative PMI from the LASSO analysis. Notably, pain management was observed to improve as RT progressed, with a greater discrepancy between cancer (33.2% with PMI &lt; 0) and non-cancer pain (73.1% with PMI &lt; 0). Breast cancer patients under 70 years of age with non-cancer pain had the highest rate of negative PMI at 86.5%, highlighting a potential deficiency in managing benign pain in younger patients. Conclusions: The study underscores the dynamic nature of pain management during RT, suggesting improvements over the treatment course yet revealing specific challenges in non-cancer pain management, particularly among younger breast cancer patients. The use of advanced statistical techniques for analysis stresses the importance of a multifaceted approach to pain management, one that incorporates both cancer and non-cancer pain considerations to ensure a holistic and improved quality of oncological care

MET inhibition sensitizes rhabdomyosarcoma cells to NOTCH signaling suppression

Rhabdomyosarcoma (RMS) is a pediatric myogenic soft tissue sarcoma. The Fusion-Positive (FP) subtype expresses the chimeric protein PAX3-FOXO1 (P3F) while the Fusion-Negative (FN) is devoid of any gene translocation. FP-RMS and metastatic FN-RMS are often unresponsive to conventional therapy. Therefore, novel therapeutic approaches are needed to halt tumor progression. NOTCH signaling has oncogenic functions in RMS and its pharmacologic inhibition through gamma-secretase inhibitors blocks tumor growth in vitro and in vivo. Here, we show that NOTCH signaling blockade resulted in the up-regulation and phosphorylation of the MET oncogene in both RH30 (FP-RMS) and RD (FN-RMS) cell lines. Pharmacologic inhibition of either NOTCH or MET signaling slowed proliferation and restrained cell survival compared to control cells partly by increasing Annexin V and CASP3/7 activation. Co-treatment with NOTCH and MET inhibitors significantly amplified these effects and enhanced PARP1 cleavage in both cell lines. Moreover, it severely hampered cell migration, colony formation, and anchorage-independent growth compared to single-agent treatments in both cell lines and significantly prevented the growth of FN-RMS cells grown as spheroids. Collectively, our results unveil the overexpression of the MET oncogene by NOTCH signaling targeting in RMS cells and show that MET pathway blockade sensitizes them to NOTCH inhibition

Role of DNA repair machinery and p53 in the testicular germ cell cancer: a review

Notwithstanding the peculiar sensitivity to cisplatin-based treatment, resulting in a very high percentage of cures even in advanced stages of the disease, still we do not know the biological mechanisms that make Testicular Germ Cell Tumor (TGCT) "unique" in the oncology scene. p53 and MDM2 seem to play a pivotal role, according to several in vitro observations, but no correlation has been found between their mutational or expression status in tissue samples and patients clinical outcome. Furthermore, other players seem to be on stage: DNA Damage Repair Machinery (DDR) , especially Homologous Recombination (HR) proteins, above all Ataxia Telangiectasia Mutated (ATM), cooperates with p53 in response to DNA damage, activating apoptotic cascade and contributing to cell "fate". Homologous Recombination deficiency has been assumed to be a Germ Cell Tumor characteristic underlying platinum-sensitivity, whereby Poly(ADP-ribose) polymerase (PARP), an enzyme involved in HR DNA repair, is an intriguing target: PARP inhibitors have already entered in clinical practice of other malignancies and trials are recruiting TGCT patients in order to validate their role in this disease. This paper aims to summarize evidence, trying to outline an overview of DDR implications not only in TGCT curability, but also in resistance to chemotherapy