Redifferentiation of BRAF V600E-Mutated Radioiodine Refractory Metastatic Papillary Thyroid Cancer After Treatment With Dabrafenib and Trametinib

xlomafota13 shared this article with you from Inoreader Redifferentiation of BRAF V600E-Mutated Radioiodine Refractory Metastatic Papillary Thyroid Cancer After Treatment With Dabrafenib and Trametinib Via radioactive iodine Cureus. 2021 Aug 27;13(8):e17488. doi: 10.7759/cureus.17488. eCollection 2021 Aug. ABSTRACT Radioactive iodine-refractory metastatic differentiated thyroid cancer (RAIR) is associated with a poor prognosis. Multikinase inhibitors have demonstrated improvement in progression-free but not overall survival in such patients, but usage is limited by significant adverse effects and the development of resistance. Clinical research has demonstrated improvement in progression-free survival with the combined use of the BRAF/MEK inhibitor in patients with metastatic melanoma and anaplastic thyroid cancer with the BRAFV600E mutation and has shown promise in redifferentiation of BRAF-positive RAIR differentiated thyroid cancer. A 58-year-old woman went to her primary care physician for a growing mass on the left side of her neck. CT imaging noted a 6 x 8 x 6 cm mixed cystic and solid mass and lymphadenopathy. Core biopsy subsequently showed metastatic papillary thyroid cancer (Stage III, PT4a/PN1b), and she underwent a total thyroidectomy with left neck dissection. She then received 204mCi 131I post-total thyroidectomy. Unfortunately, her thyroglobulin continued to increase post-radioactive iodine (RAI) treatment, indicating persistent and/or recurrent thyroid cancer. An RAI-131 whole-body scan on the thyrogen protocol showed no significant RAI uptake. A fluorodeoxyglucose (FDG)-positron emission tomography (PET) CT scan was then performed, which sho wed recurrent metastatic disease with hypermetabolism noted in the left thyroid bed and FDG-avid bilateral cervical lymph nodes and pulmonary nodules. Given these findings, her cancer was classified as radioactive iodine refractory (RAIR). Molecular testing indicated the BRAFV600E mutation. After a discussion with the patient, it was decided to initiate therapy with a BRAF inhibitor (dabrafenib 150 mg twice a day) and MEK inhibitor (trametinib 2 mg once a day) in an attempt to redifferentiate RAIR. Repeat RAI-131 thyrogen whole body scan one month after initiation of therapy demonstrated left level 2 cervical lymphadenopathy radioiodine uptake. The patient subsequently received 216 mCi 131I treatment given evidence of redifferentiation. Her post-treatment scan indicated additional uptake in a left lower lobe pulmonary nodule as well as a left paratracheal mass indicating successful RAI-131 uptake by metastases. Her thyroglobulin level, six months post-RAI, decr eased to 4.0 indicating an encouraging response. Further surveillance, including imaging studies, is planned. This case illustrates the re-differential potential for dabrafenib and trametinib treatment in patients with BRAFV600E-mutated RAIR differentiated thyroid cancer. This therapy has been shown to be successful in small series of patients and could potentially be offered to RAIR patients with the BRAFV600E mutation as an alternative to multikinase treatment given its favorable side-effect profile. PMID:34595070 | PMC:PMC8465644 | DOI:10.7759/cureus.17488 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Conjunctivoductivo‐Dacryocystorhinostomy: A Novel Surgery for Intractable Canalicular Obstruction

xlomafota13 shared this article with you from Inoreader Conjunctivoductivo‐Dacryocystorhinostomy: A Novel Surgery for Intractable Canalicular Obstruction Via The Laryngoscope View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Novel function of fluvastatin in attenuating oxidized low-density lipoprotein-induced endothelial cell ferroptosis in a glutathione peroxidase4- and cystine-glutamate antiporter-dependent manner

xlomafota13 shared this article with you from Inoreader Novel function of fluvastatin in attenuating oxidized low-density lipoprotein-induced endothelial cell ferroptosis in a glutathione peroxidase4- and cystine-glutamate antiporter-dependent manner Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1275. doi: 10.3892/etm.2021.10710. Epub 2021 Sep 8. ABSTRACT Oxidized low-density lipoprotein (ox-LDL) induces endothelial cell apoptosis and dysfunction. Statins are drugs that are clinically used to lower serum cholesterol levels, and they have been shown to exert vascular protective effects. In the present study, human umbilical vein endothelial cells were transfected with scramble control siRNA or siRNA specific for glutathione peroxidase (GPx)4 or cystine-glutamate antiporter (xCT). MTT, Matrigel and Transwell assays were used to evaluate cell proliferation, tube formation and migration, respectively. The levels of TNF-α, IL-α, 4-hydroxynonenal, GPx4 and xCT expression were detected by western blot analysis. It was demonstrated that ox-LDL promoted cytokine production and reduced the proliferation, migration and angiogenesis of endothelial cells. It was also observed that ox-LDL decreased GPx4 and xC T expression and induced ferroptosis. Furthermore, the inhibition of ferroptosis by deferoxamine mesylate attenuated ox-LDL-induced endothelial cell dysfunction and restored ox-LDL-decreased GPx4 and xCT expression. Consistent with these results, GPx4 and xCT knockdown by siRNA transfection aggravated ox-LDL-induced endothelial cell dysfunction and inhibition of proliferation. To the best of our knowledge, the present study was the first to discover that fluvastatin may protect endothelial cells from ox-LDL-induced ferroptosis and dysfunction. Furthermore, knockdown of GPx4 and xCT expression blunted the protective effects of fluvastatin on ox-LDL-treated endothelial cells. These data indicated a novel function of fluvastatin in the protection of endothelial cells from ox-LDL-induced ferroptosis, the mechanism of which involves the regulation of GPx4 and xCT. PMID:34594412 | PMC:PMC8456483 | DOI:10.3892/etm.2021.10710 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

miR-122-5p downregulation attenuates lipopolysaccharide-induced acute lung injury by targeting IL1RN

xlomafota13 shared this article with you from Inoreader miR-122-5p downregulation attenuates lipopolysaccharide-induced acute lung injury by targeting IL1RN Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1278. doi: 10.3892/etm.2021.10713. Epub 2021 Sep 8. ABSTRACT MicroRNAs (miRs) and inflammatory cytokines can induce acute lung injury (ALI), which can develop into acute respiratory distress syndrome in severe cases. Previous research has revealed that miR-122-5p participates in the development of ALI, and that its expression is positively associated with ALI. However, the mechanism by which miR-122-5p contributes to ALI remains to be determined. In the current study, TargetScan and dual luciferase reporter gene assays were used to confirm that IL-1 receptor antagonist (IL1RN) was a target of miR-122-5p. Subsequently, by referring to previous literature, a lipopolysaccharide (LPS)-induced ALI cell model was established. A549 cells were transfected with mimic control or miR-122-5p mimics for 24 h, and 10 µg LPS was used to treat the transfected cells for 12 h. The results revealed that miR-122-5p mimics dec reased cell viability and promoted apoptosis. Lactate dehydrogenase (LDH) release assays indicated that miR-122-5p mimics increased LDH release. ELISA demonstrated that miR-122-5p mimics promoted TNF-α, IL-1β and IL-6 expression levels. A549 cells were transfected with inhibitor control, miR-122-5p inhibitor, miR-122-5p inhibitor + control-small interfering (si)RNA or miR-122-5p inhibitor + IL1RN-siRNA for 24 h, after which the cells were treated with 10 µg LPS for 12 h. The results revealed that the effects of the miR-122-5p inhibitor were the opposite of those of the miR-122-5p mimic. All the effects of miR-122-5p inhibitor on LPS-treated A549 cells were significantly reversed by IL1RN-siRNA. Overall, the results highlighted miR-122-5p as a potential novel target for the treatment of ALI. PMID:34594415 | PMC:PMC8456493 | DOI:10.3892/etm.2021.10713 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

HPV vaccine for men: Where to? (Review)

xlomafota13 shared this article with you from Inoreader HPV vaccine for men: Where to? (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1266. doi: 10.3892/etm.2021.10701. Epub 2021 Sep 7. ABSTRACT Human papillomavirus (HPV) is one of the most widespread human pathogens. For a long time, it was treated as an opportunistic infection, but it is in actuality one of the most dangerous carcinogens. It is responsible for numerous malignancies: Cervical, penile, oropharyngeal, vaginal, vulvar and some anal neoplasia. The need for a long-term solution was evident and thus HPV vaccines were proven to be a viable solution. Women and men who have sex with men, and young men are included in the vaccination template. A thorough review using PubMed and other databases that included articles on vaccine templates and targeted male patients was carried out. After review of all of the studies conducted on this subject, there is a clear benefit for HPV vaccination for men. Yet, even with the introduction of a national vaccine program for HPV for women and girl s in most developed countries, regarding the male vaccine program, few countries have established a national program. Still, a gender-neutral vaccine remains a controversial issue. It is important to monitor the impact of HPV vaccine in men and the benefits that occur, to inform and spread the results in order to implement this vaccine program worldwide. Any monitoring plan regarding the HPV vaccination must include HPV prevalence, anogenital warts, and anal cancer. The largest impact regarding the range of this type of vaccine is the surveillance of the specific targeted population. HPV vaccine is a very efficient immunization method. Women are obviously the first target, but there are still many contradictions regarding men. Most of the reasons reside in the cost-efficiency aspect, but there is still great debate regarding the most efficient vaccine in the male population. PMID:34594403 | PMC:PMC8456458 | DOI:10.3892/etm.2021.10701 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Distortion Product Otoacoustic Emission (DPOAE) Growth in Aging Ears with Clinically Normal Behavioral Thresholds

xlomafota13 shared this article with you from Inoreader Distortion Product Otoacoustic Emission (DPOAE) Growth in Aging Ears with Clinically Normal Behavioral Thresholds Via Journal of the Association for Research in Otolaryngology Abstract Age-related hearing loss (ARHL) is a devastating public health issue. To successfully address ARHL using existing and future treatments, it is imperative to detect the earliest signs of age-related auditory decline and understand the mechanisms driving it. Here, we explore early signs of age-related auditory decline by characterizing cochlear function in 199 ears aged 10–65 years, all of which had clinically defined normal hearing (i.e., behavioral thresholds ≤ 25 dB HL from .25 to 8 kHz bilaterally) and no history of noise exposure. We characterized cochlear function by measuring behavioral thresholds in two paradigms (traditional audiometric thresholds from .25 to 8 kHz and Békésy tracking thresholds from .125 to 20 kHz) and distortion product otoacoustic emission (DPOAE) growth functions at f2 = 2, 4, and 8 kHz. Behavioral thresholds through a standard clinical frequency range (up to 8 kHz) s howed statistically, but not clinically, significant declines across increasing decades of life. In contrast, DPOAE growth measured in the same frequency range showed clear declines as early 30 years of age, particularly across moderate stimulus levels (L2 = 25–45 dB SPL). These substantial declines in DPOAE growth were not fully explained by differences in behavioral thresholds measured in the same frequency region. Additionally, high-frequency Békésy tracking thresholds above ~11.2 kHz showed frank declines with increasing age. Collectively, these results suggest that early age-related cochlear decline (1) begins as early as the third or fourth decade of life, (2) is greatest in the cochlear base but apparent through the length of the cochlear partition, (3) cannot be detected fully by traditional clinical measures, and (4) is likely due to a complex mix of etiologies. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Drug approval: Selpercatinib and pralsetinib - RET-altered thyroid cancer

xlomafota13 shared this article with you from Inoreader Drug approval: Selpercatinib and pralsetinib - RET-altered thyroid cancer Via Association française pour l'étude du cancer Bull Cancer. 2021 Sep 28:S0007-4551(21)00301-5. doi: 10.1016/j.bulcan.2021.05.009. Online ahead of print. NO ABSTRACT PMID:34598787 | DOI:10.1016/j.bulcan.2021.05.009 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prophylactic fasciotomy of the anterolateral thigh donor site in head and neck reconstruction

xlomafota13 shared this article with you from Inoreader Prophylactic fasciotomy of the anterolateral thigh donor site in head and neck reconstruction Via American Journal of Otolaryngology Publication date: January–February 2022 Source: American Journal of Otolaryngology, Volume 43, Issue 1 Author(s): Katherine Sadaniantz, Lauren Daly, Jing Bai Qin, Jeremiah Tracy View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Medial patellar plica syndrome

xlomafota13 shared this article with you from Inoreader Medial patellar plica syndrome Via Neuroradiology Cases Clinically young patient with anteromedial knee pain. MRI shows a well-defined low signa l intensity band running across medial patellofemoral recess. However there is no obvious associated bone marrow oedema involving medial articulating facet of patella or medial femoral trochlea.  Associated joint effusion. Medial plica mentioned in the report with joint effusion. Medial plica syndrome Synonym: synovial plicae of the knee. Common cause of anterior knee pain typically present with pain on anteromedial aspect of the knee above the joint line associated with crepitation, catching and locking sensations.  Typically involves young with athletic background.  There are actually synovial invaginations as a part of remnants of embryological development. They are present in over 70% of individuals and are mostly asymptomatic. However can become inflamed and symptomatic. They can undergo fibrosis secondary to repeate d inflammation making them non-stretchable. In symptomatic patients, medial plica seen as low signal intensity band on T1 as well as T2-weighted images with an associated chondral defect involving medial articulating facet of patella. Treatment is mainly conservative, physiotherapy and steroid injections. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Morel-Lavallée lesion MRI

xlomafota13 shared this article with you from Inoreader Morel-Lavallée lesion MRI Via Neuroradiology Cases Clinically RTA, run over by tractor. This MRI study shows a focal well defined lentiform shaped subcutaneous collection on medial aspect of knee joint superficial to the superficial fascia. Collection is clear, hypo intense on T1-weighted images without any septation or loculation. No obvious high signal intensity methaemoglobin staining on T1-weighted images to suggest any haematoma. Morel-Lavallée lesion These are focal well defined lentiform shaped subcutaneous serous collections commonly encountered during MRI knee joint in the setting of severe trauma. However these lesions are typically described in thigh as well defined collection overlying the greater trochanter of the femur, tensor facia lata.  These actually localized haemolymphatic collections secondary to closed degloving injuries, where the skin and subcutaneous fatty tissue abruptly separate from the underlying fascia owing to trauma. The potential space thus created superficial to the superficial fascia is filled by serous fluid, some times frank blood. Similar collection secondary to similar biomechanical forces are described in lumbar region and over the scapula as well.  The accumulated collection usually needs nothing to be done, resolves spontaneously. However may persist longer if gets organized and encapsulated. The conservative management is with compression bandages. Surgical drainage may be sufficient for larger collection. However, the capsule may need to be resected to prevent re-accumulation if it is long standing and encapsulated collection with thick organized wall.  View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Impact of Depth of Invasion (According to Layer) on Lymph Node Metastasis in Buccal Mucosa Cancers

xlomafota13 shared this article with you from Inoreader Impact of Depth of Invasion (According to Layer) on Lymph Node Metastasis in Buccal Mucosa Cancers Via Otolaryngology Indian Abstract (1) To study layer of invasion as predictor of cervical lymph node metastasis. (2) To decide a cut off depth according to layer of invasion for neck dissection. It is a prospective study with sample size of 220 patients at tertiary care hospital with previously untreated operable buccal mucosa carcinoma over period of 21 months. The factors considered under the study were Tumor layer of invasion, lymph node metastasis, Ultrasonography doppler neck, CT scan and gender. Wide excision of the lesion and reconstruction was done. Histopathological analysis of resected specimen were recorded as part of data collection for all the cases. Quantitative data represented using Mean ± SD (Standard Deviation) and median and interquartile range compared using Chi square test. Standard principles of univariate analysis was used according to statistical methods. Depth when measured according to layer of invasion, was significantly associated with lymph no de metastasis with 89% of the muscle as layer of invasion being Lymph node positive (p = 0.009). There is 1.39 times chances of lymph nodal metastasis in patients with muscle invasion as compared to submucosal invasion. Tumour layer of invasion plays important role in predicting chances of nodal metastasis in clinically N0 neck in buccal mucosa cancer. According to the study, we should electively proceed with ipsilateral lymph node dissection once the layer of tumour invasion is muscle. This study is limited by sample size and short duration of one year and nine months. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.