Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Monday, February 7, 2022

Machine learning directed sentinel lymph node biopsy in cutaneous head and neck melanoma

xlomafota13 shared this article with you from Inoreader

Abstract

Background

The specificity of sentinel lymph node biopsy (SLNB) for detecting lymph node metastasis in head and neck melanoma (HNM) is low under current National Comprehensive Cancer Network (NCCN) treatment guidelines.

Methods

Multiple machine learning (ML) algorithms were developed to identify HNM patients at very low risk of occult nodal metastasis using National Cancer Database (NCDB) data from 8466 clinically node negative HNM patients who underwent SLNB. SLNB performance under NCCN guidelines and ML algorithm recommendations was compared on independent test data from the NCDB (n = 2117) and an academic medical center (n = 96).

Results

The top-performing ML algorithm (AUC = 0.734) recommendations obtained significantly higher specificity compared to the NCCN guidelines in both internal (25.8% vs. 11.3%, p < 0.001) and external test populations (30.1% vs. 7.1%, p < 0.001), while achieving sensitivity >97%.

Conclusion

Machine learning can identify clinically node negative HNM patients at very low risk of nodal metastasis, who may not benefit from SLNB.

View on the web

Harmine reinforces the effects of regorafenib on suppressing cell proliferation and inducing apoptosis in liver cancer cells

xlomafota13 shared this article with you from Inoreader

Exp Ther Med. 2022 Mar;23(3):209. doi: 10.3892/etm.2022.11132. Epub 2022 Jan 7.

ABSTRACT

The overall outcomes for patients with advanced liver cancer are far from satisfactory, and the development of more effective therapeutic strategies for liver cancer is required. Sulforhodamine blue and colony formation assays were performed to detect the proliferation of liver certain cancer cells, including HepG2 and Hep3B. Western blotting was also preformed to detect the expression of indicated proteins, including cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerase, dual-specificity tyrosine phosphorylation kinase 1A (DYRK1A), PARP-1/2, GAPDH, myeloid cell leukemia-1, phosphorylated-AKT (Ser473), caspase-3, α-tubulin and AKT. PI staining was used to detect cell death. In the present study, DYRK1A knockdown significantly enhanced the anti-liver cancer effect of regorafenib in vitro. Furthermore, DYRK1A inhibitor harmine together with regorafenib provided synergistic anti-liver cancer activity by suppressing cell proliferation. In addition, harmine significantly enhanced regorafenib-induced cell death in liver cancer cells. It has been reported that AKT signaling is activated in regorafenib-resistant cancer cells and plays a crucial role in the regulation of cellular sensitivity to regorafenib. In the present study, AKT was activated in regorafenib-treated cells, and harmine could suppress the activation of AKT and reinforce the anti-cancer effects of regorafenib via regulating AKT in liver cancer cells. These data indicated that harmine enhanced the anti-cancer effects of regorafenib on suppressing cell proliferation and inducing apoptosis in liver cancer cells via regulating the activation of AKT, and harmine plus regorafenib may be a potential therapeutic regimen for treating patients with liver cancer.

PMID:35126712 | PMC:PMC8796640 | DOI:10.3892/etm.2022.11132

View on the web

Benefits and adverse events of melatonin use in the elderly (Review)

xlomafota13 shared this article with you from Inoreader

Exp Ther Med. 2022 Mar;23(3):219. doi: 10.3892/etm.2022.11142. Epub 2022 Jan 14.

ABSTRACT

Melatonin is a hormone secreted by the pineal gland in accordance with the circadian rhythm when the light level decreases. Reduction of melatonin secretion with age may be associated with physiological aging in neurodegenerative diseases by affecting the suprachiasmatic nucleus or of the neuronal pathways of transmission to the pineal gland. A significant decrease in melatonin synthesis has been reported in various disorders and diseases, including cardiovascular diseases, metabolic disorders (particularly diabetes type 2), cancer and endocrine diseases. In addition to the fact, that melatonin is a sleep inducer, it also exerts cytoprotective properties as an antioxidant and free radical scavenger. The therapeutic role of melatonin has been demonstrated in sleep disorders, eye damage and cardiovascular disease. The association between melatonin a nd β-blockers has had a positive impact on sleep disorders in clinical trials. Previous studies have reported the anti-inflammatory effect of melatonin by adjusting levels of pro-inflammatory cytokines, including interleukin (IL)-6, IL-1β and tumor necrosis factor-α. Melatonin treatment has been demonstrated to decrease IL-6 and IL-10 expression levels and efficiently attenuate T-cell proliferation. Currently, there is an inconsistency of scientific data regarding the lowest optimal dose and safety of melatonin for long-term use. The aim of the present review was to summarize the evidence on the role of melatonin in various clinical conditions and highlight the future research in this area.

PMID:35126722 | PMC:PMC8796282 | DOI:10.3892/etm.2022.11142

View on the web

Efficiency of platelet-rich plasma therapy for healing sports injuries in young athletes

xlomafota13 shared this article with you from Inoreader

Exp Ther Med. 2022 Mar;23(3):215. doi: 10.3892/etm.2022.11139. Epub 2022 Jan 11.

ABSTRACT

In recent years, platelet-rich plasma (PRP) therapy has been a subject of controversy in orthopedics field. Our objective was to assess the efficiency of PRP therapy for patients who have suffered grade 2 meniscal lesions and grade 2 anterior cruciate ligament (ACL) lesions, graded by magnetic resonance imaging (MRI). A retrospective observational study was conducted, which included 72 young recreational athletes who had been diagnosed with grade 2 meniscal injury, graded using MRI, that benefited from PRP therapy as an enhancement of the primary treatment, after cast immobilization. The Lysholm score, the pain intensity and the resuming of the physical activity before the PRP treatment and one month after were analyzed. Our study revealed that patients had an improved subjective perception of pain after PRP therapy and an improvement of the Lysho lm score. Concurrently, 83.3% of patients could return to sports and daily physical activity. It can be concluded that PRP therapy is a safe, easy to manage treatment, efficient for pain relief and in resuming of sports activities for young recreational athletes who have sustained partial meniscal or ACL tears. In terms of pain relief, it appears that the PRP therapy could be more efficient for young patients with ACL injuries.

PMID:35126718 | PMC:PMC8796279 | DOI:10.3892/etm.2022.11139

View on the web

Identification of key pathways and genes in vestibular schwannoma using bioinformatics analysis

xlomafota13 shared this article with you from Inoreader

Exp Ther Med. 2022 Mar;23(3):217. doi: 10.3892/etm.2022.11141. Epub 2022 Jan 13.

ABSTRACT

The aim of the present study is to identify novel promising marks and targets of diagnosis, therapy and prognosis for patients with vestibular schwannoma at the molecular level. The gene expression profiles of GSE54934, GSE39645 and GSE56597 datasets were obtained respectively from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified by comparing between gene expression profiles of the vestibular schwannoma tissues and normal tissues. Subsequently, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analysis were performed. The function and pathway enrichment analysis were performed for DEGs with DAVID. Reverse transcription-quantitative PCR were conducted to confirm the expression of BCL2, AGT, IL6 and ITGA2 in human Schwann cells and vestibular schwannoma cells. A total of 4,025, 1,1291 and 1,513 DEGs were identified from GSE54934, GSE56597 and GSE39645 datasets, respectively. GO and KEGG analysis showed that the mutual upregulated genes were mainly enriched in cell division, mitotic nuclear division, and transition of mitotic cell cycle, whilst mutual downregulated genes were enriched in chemical synaptic transmission, neurotransmitter transport, and synaptic vesicle membrane. Subsequently, 20 genes, including BCL2, AGT, IL6 and ITGA2 were selected as hub genes with high degrees after PPI network analysis. The significant differential expression of those genes were detected among vestibular schwannoma tissues compared with normal nerve tissues. In conclusion, BCL2, AGT, IL6 and ITGA2 are significantly higher expressed in vestibular schwannoma tissues compared with human Schwann tissues. The DEGs identified in the present study provide novel targets for the diagnosis and treatment of vestibular schwannoma.

PMID:35126720 | PMC:PMC8796280 | DOI:10.3892/etm.2022.11141

View on the web

Role of antioxidants and oxidative stress in the evolution of acute pancreatitis (Review)

xlomafota13 shared this article with you from Inoreader

Exp Ther Med. 2022 Mar;23(3):197. doi: 10.3892/etm.2022.11120. Epub 2022 Jan 5.

ABSTRACT

Acute pancreatitis (AP) is a severe disease with a high prevalence and 3 to 15% mortality worldwide, which can represent an important challenge for the physician. Oxidative stress and antioxidants are involved in AP progression. The mechanisms responsible for the onset and progression of AP are still poorly understood. Previous studies have highlighted the important contribution of antioxidants and oxidative stress in AP. The existence of a relationship between oxidative stress and antioxidants in AP is unquestionable, although a more accurate understanding of the mechanistic pathways involved is required to create a solid basis for potential prevention or treatment strategies. Further investigation is needed to clarify the role of antioxidant status and the severity of AP and to determine the association between oxidative stress and pancreatic enz yme activities. Antioxidant therapy may represent an interesting option for the management of patients with AP, although additional information about the effectiveness of this potential treatment is required.

PMID:35126700 | PMC:PMC8794551 | DOI:10.3892/etm.2022.11120

View on the web

From chronic pruritus to neuroendocrine tumor: A case report

xlomafota13 shared this article with you from Inoreader

Exp Ther Med. 2022 Mar;23(3):189. doi: 10.3892/etm.2022.11112. Epub 2022 Jan 4.

ABSTRACT

Chronic pruritus is a major and distressing symptom of many diseases of dermatological, neurological, psychogenic or systemic origin. This chronic itch could be a presenting sign of malignancy; therefore, paraneoplastic pruritus has also been associated with neuroendocrine tumors (NETs). This article focuses on a patient presenting with chronic pruritus for the past 12 months and who received numerous treatment schemes with very poor clinical improvement, that presented in the hospital for worsening of the chronic pruritus associated with skin rash and significant weight loss (approximately 6 kg over a 2-month period). The laboratory tests showed iron deficiency anemia, eosinophilia and negative tumor markers. In order to investigate the hypoanabolic and anemic syndromes, upper gastrointestinal endoscopy and colonoscopy, which showed no lesions or tumors, were employed. Skin biopsy was performed and antihistaminic and local steroid treatment was initiated. The patient's status worsened within a week and the patient was started on systemic steroid treatment with poor results. Computer tomography was performed to identify any tumor(s) located either in the pelvis or abdomen. A lesion was found in the terminal ileum, identified as a hypervascularized associating bulky lymphadenopathy. The patient was transferred to the surgical ward where right hemicolectomy with manual ileotransverse anastomosis L-L was performed. The histopathological result confirmed NET G2. The patient clinically improved, the skin lesions resolved and the itchiness disappeared. The general status improved significantly. NET G2 diagnosing was possible due to the atypic paraneoplastic sign: chronic pruritus. This case study highlights the association between itch and malignancy and presents an atypical way of NET presentation when all tumor markers remain neg ative.

PMID:35126692 | PMC:PMC8794552 | DOI:10.3892/etm.2022.11112

View on the web

Cytokines and Inflammation in Meniere Disease

xlomafota13 shared this article with you from Inoreader

Clin Exp Otorhinolaryngol. 2022 Feb 8. doi: 10.21053/ceo.2021.00920. Online ahead of print.

ABSTRACT

Meniere disease (MD) is a rare set of conditions associated with the accumulation of endolymph in the cochlear duct and the vestibular labyrinth with a decrease of endocochlear potential. It is considered a chronic inflammatory disorder of the inner ear with a multifactorial origin. The clinical syndrome includes several groups of patients with a core phenotype: sensorineural hearing loss, episodes of vertigo, and tinnitus with a non-predictable course. Genetic factors and the innate immune response seem to play a central role in the pathophysiology of the condition. Autoimmune MD should be diagnosed if a patient fulfills the diagnostic criteria for MD and one of the following autoimmune disorders: autoimmune thyroid disease, psoriasis, autoimmune arthritis, ankylosing spondylitis, or systemic lupus erythematosus. We summarize the evide nce to support autoimmune MD as an endophenotype in bilateral MD associated with the allelic variant rs4947296 and nuclear factor-kappa B (NF-κB)-mediated inflammation, the role of cytokines (particularly interleukin-1β and tumor necrosis factor-α) in defining a subset of patients with autoinflammation, and the potential role of cytokines as biomarkers to distinguish between patients with MD and vestibular migraine. Finally, we also introduce a list of potential drugs that could regulate the immune response in MD with potential for repurposing in clinical trials.

PMID:35124944 | DOI:10.21053/ceo.2021.00920

View on the web

Oral administration of megestrol acetate can increase fat graft survival in a rat model

xlomafota13 shared this article with you from Inoreader

J Plast Reconstr Aesthet Surg. 2022 Jan 16:S1748-6815(22)00018-3. doi: 10.1016/j.bjps.2022.01.004. Online ahead of print.

ABSTRACT

Insufficient and inconsistent survival is a significant shortcoming of fat grafts. Reportedly, megestrol acetate (MA) could induce proliferation, migration, and adipogenic differentiation of adipose-derived stem cells in vitro. Thus, we tested whether MA could promote fat graft survival in a rat model. Twenty-eight Sprague-Dawley rats (8 weeks old, male) were divided into two groups: experimental (MA group, n = 14) and control (n = 14). The inguinal fat pad (1 g) was extracted en bloc and re-implanted under the scalp in both groups. MA (100 mg/kg/day) was administered orally for 14 postoperative days in the experimental group. After 6 weeks, the volume and weight of the grafted fat were measured. Histologic examination with hematoxylin and eosin (HE) and real-time polymerase chain reaction (PCR) for vascula r endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and CCAAT/enhancer-binding protein alpha (C/EBP-α) were performed. Perilipin staining was performed to check the viability of grafted fat. Graft fat volume was greater in the MA group, compared with that in the control (P = 0.023). The MA group also had more viable cells, including more adipocytes, and less fibrosis or vacuoles than the control on HE and perilipin staining. MA upregulated the expression of FGF2 (P<0.001), VEGF (P = 0.008), and C/EBP-α (P = 0.002) at the second postoperative week. MA increased survival of grafted fat in an animal model. Increased vascularization and adipogenesis were related to these results. Further human clinical trials are necessary to evaluate adjunctive oral administration of MA after fat grafting to promote graft survival.

PMID:35125304 | DOI:10.1016/j.bjps.2022.01.004

View on the web

Electroacoustic Evaluation of Smartphone-Based Hearing Aid Applications

xlomafota13 shared this article with you from Inoreader

Clin Exp Otorhinolaryngol. 2022 Feb 8. doi: 10.21053/ceo.2021.01004. Online ahead of print.

ABSTRACT

OBJECTIVES: This study evaluated the electroacoustic characteristics of smartphone-based hearing aid applications (apps).

METHODS: We investigated hearing aid apps based on processing delay measurements, hearing instrument testing, simulated real ear measurements, and a head-and-torso simulator.

RESULTS: Many apps exceeded the recommended level for processing delay. Hearing instrument testing showed the highest amplification characteristics and the best sound quality when a hearing aid was used, followed by the high-end apps and then the low-end apps. The simulated real ear measurements results showed that the high-end apps had a better ability to match the amplification targets than the low-end apps, but there was no consistent pattern among apps when controlling the output. Only a few apps could improve the signal-to-noise ratio in the head-and-torso simulator.

CONCLUSION: Most of the apps showed relatively poor electroacoustic performance in comparison with hearing aids. Generalizing access to hearing care through hearing aid apps induces a wide diversity of hearing performance with no fixed standard for reliability. However, we expect their overall quality to improve over the next few years.

PMID:35124945 | DOI:10.21053/ceo.2021.01004

View on the web

Breast and abdominal scarring after DIEP flap breast reconstruction: An exploration of patient-reported scar quality

xlomafota13 shared this article with you from Inoreader

J Plast Reconstr Aesthet Surg. 2022 Jan 14:S1748-6815(22)00002-X. doi: 10.1016/j.bjps.2021.12.003. Online ahead of print.

ABSTRACT

PURPOSE: This research aimed to explore factors associated with patient-reported breast and abdominal scar quality after deep inferior epigastric perforator (DIEP) flap breast reconstruction (BR).

MATERIAL AND METHODS: This study was designed as a descriptive cross-sectional survey in which women after DIEP flap BR were invited to complete an online survey on breast and abdominal scarring. The online survey was distributed in the Netherlands in several ways in order to reach a diverse population of women. Outcomes were assessed with the Patient Scale of the Patient and Observer Scar Assessment Scale (POSAS). Additional items were assessed with a numeric rating scale (NRS).

RESULTS: A total of 248 women completed the survey. There was a statistically significant worse POSAS scar appraisal for the abdominal scar compared with the breast scar. The vast majority of women reported high scores on at least one scar characteristic of their breast scar or abdominal scar. Overall, color, stiffness, thickness, and irregularity scored higher than pain and itching. Women were only moderately positive about the size, noticeability, location, and the information provided regarding scarring.

CONCLUSION: It is crucial to address the inevitability of scars in patient education before a DIEP flap BR, with a particular focus on the abdominal scar, as women experience abdominal scars significantly worse than their breast scars. Providing more information on the experience of other women and the expected appearance will contribute to having realistic expectations while allowing them to make well-informed decisions.

PMID:35125306 | DOI:10.1016/j.bjps.2021.12.003

View on the web