Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Δευτέρα 7 Φεβρουαρίου 2022

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

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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.

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Col9a2 gene deletion accelerates the degeneration of intervertebral discs

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Exp Ther Med. 2022 Mar;23(3):207. doi: 10.3892/etm.2022.11130. Epub 2022 Jan 7.

ABSTRACT

As an essential component of the extracellular matrix (ECM) in cartilage, the α2 chain of type IX collagen (Col9a2), has been implicated in human intervertebral disc degeneration (IVDD). However, the precise role of the Col9a2 gene in the pathogenesis of IVDD has remained elusive. In the present study, the spines of Col9a2-deficient (Col9a2-/-) mice were systematically analyzed and compared with wild-type control mice using micro-CT (µCT), histomorphology, immunofluorescence, immunohistochemistry and reverse transcription-quantitative PCR (RT-qPCR). µCT analysis revealed that endplate (EP) osteochondral remodeling in the Col9a2-/- group was accompanied by a significant increase in EP porosity. Likewise, histopathological staining at 12 weeks revealed that the Col9a2-/- mice exhibited a marked early-stage IVDD phe notype, including EP sclerosis, calcification and annulus fibrosus rupture. The immunofluorescence results indicated that Col9a2 was extensively expressed in the IVDs, whereas it was barely detectable in Col9a2-/- mice. Immunohistochemical and RT-qPCR analyses demonstrated that the expression levels of Col2a1 and Aggrecan in the IVDs of Col9a2-/- mice were significantly decreased. In addition, the levels of Mmp13, ADAM metallopeptidase with thrombospondin type 1 motif 5, Col10a1 and Runx family transcription factor 2 were significantly elevated. These results suggested that deletion of the Col9a2 gene led to osteochondral remodeling of cartilage EP and suppressed ECM synthesis, accelerating matrix degradation and chondrocyte hypertrophy in the IVD tissue.

PMID:35126710 | PMC:PMC8796617 | DOI:10.3892/etm.2022.11130

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

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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

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An original method of simulating the articular cartilage in the context of in vitro biomechanical studies investigating the proximal femur

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Exp Ther Med. 2022 Mar;23(3):202. doi: 10.3892/etm.2022.11125. Epub 2022 Jan 5.

ABSTRACT

Biomechanical testing is a necessity given the development of novel implants used in the osteosynthesis of hip fractures. The purpose of biomechanical testing is to recreate realistic conditions similar to the in vivo conditions. Although biomechanical testing of hip arthroplasty has been standardized since the 1970s, there is no consensus at present on testing methodology for osteosynthesis of hip fractures. Most biomechanical studies examining the fractures of the proximal femur in order to optimize implants opt for loading the bone-implant ensemble directly on the femoral head or using a metallic loading part. This loading technique fails to perform a mechanical stress distribution similar to in vivo conditions, which could alter the outcome. The present study aimed to design loading/unloading cups with mechanical properties that r esemble those of the cartilage at the hip level. Through the impression and scanning of the cast models obtained, a digital 3D model was created in STL format and this was processed in order to obtain the computer numerical control (CNC) trajectories of the printing head. For prototyping using additive manufacturing technology, a thermoplastic polymer with biochemical properties, such as tensile strength, that resemble those of the adult hip and a Stratasys FORTUS 250 mc CNC machine were used. Loading/unloading cups with similar anatomy and biomechanical forces compared with those of the adult hip were created, which allowed the experimental simulation of the conditions during walking.

PMID:35126705 | PMC:PMC8794553 | DOI:10.3892/etm.2022.11125

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Insulin-like growth factor-1: A potential target for bronchopulmonary dysplasia treatment (Review)

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Exp Ther Med. 2022 Mar;23(3):191. doi: 10.3892/etm.2022.11114. Epub 2022 Jan 5.

ABSTRACT

Bronchopulmonary dysplasia (BPD) is a common respiratory disorder among preterm infants, particularly low-birth-weight infants (LBWIs) and very-low-birth-weight infants (VLBWIs). Although BPD was first reported 50 years ago, no specific drugs or efficient measures are yet available for prevention or treatment. Insulin-like growth factor-1 (IGF-1) belongs to the insulin family. It promotes mitosis and stimulates cell proliferation and DNA synthesis, the primary factors involved in pulmonary development during the fetal and postnatal periods. Several studies have reported that IGF-1 exerts certain effects on BPD genesis and progression by regulating BPD-related biological processes. In addition, exogenous addition of IGF-1 can alleviate lung inflammation, cell apoptosis and eliminate alveolar development disorders in children with BPD. These findings suggest that IGF-1 could be a new target for treating BPD. Here, we summarize and analyze the definition, pathogenesis, and research status of BPD, as well as the pathogenesis of IGF-1 in BPD and the latest findings in related biological processes.

PMID:35126694 | PMC:PMC8794548 | DOI:10.3892/etm.2022.11114

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

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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

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

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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

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Telmisartan inhibits bladder smooth muscle fibrosis in neurogenic bladder rats

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Exp Ther Med. 2022 Mar;23(3):216. doi: 10.3892/etm.2022.11140. Epub 2022 Jan 11.

ABSTRACT

Hypertension is associated with bladder symptoms. The present study investigated whether an angiotensin receptor blocker could improve the symptoms and pathological changes associated with a neurogenic bladder (NB). A Sprague-Dawley rat model of NB was constructed. Rats in the sham and model groups were gavaged with saline, and rats in the treatment group were gavaged with telmisartan. Urodynamic parameters, including maximum cystometric capacity, residual urine volume, bladder wet weight, bladder compliance and detrusor pressure, were detected. Masson and H&E staining were performed to assess bladder fibrosis and histopathological changes. The expression levels of basic fibroblast growth factor (bFGF), TGF-β1, Collagen I, Collagen III, and α-smooth muscle actin (α-SMA) were also measured by reverse transcription-quantitative PCR, western b lotting and immunohistochemistry. The model rats exhibited symptoms and pathological changes associated with NB. Treatment with telmisartan reduced maximum cystometric capacity, residual urine volume, bladder compliance and bladder wet weight, and increased detrusor pressure in model rats. The tissue staining results showed that telmisartan exerted an antifibrotic effect. In addition, telmisartan inhibited the expression of bFGF, TGF-β1, Collagen I, Collagen III and α-SMA in model rats. Therefore, the results of the present study indicated that telmisartan may serve as a potential therapeutic agent for NB.

PMID:35126719 | PMC:PMC8796288 | DOI:10.3892/etm.2022.11140

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

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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

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Cytokines and Inflammation in Meniere Disease

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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

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Electroacoustic Evaluation of Smartphone-Based Hearing Aid Applications

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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

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