Sunday, June 13, 2021

Comparing prognostic utility between the 8th edition of TNM staging system and the lymph node ratio for oral squamous cell carcinoma

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Abstract

Background

Lymph node metastasis in oral squamous cell carcinoma (OSCC) is associated with poor prognosis. The 8th edition of TNM has implemented new nodal staging criteria. We assess the prognostic utility of the lymph node ratio (LNR) and compare it to that of pN in the TNM 8th edition.

Methods

One hundred and forty-two patients with OSCC were retrospectively studied. Nodal staging was performed using the TMN 8th edition and the prognostic value of the LNR in terms of overall survival (OS) and disease-free survival (DFS) was evaluated.

Results

Fifty-seven patients were eligible for inclusion. The LNR was independently prognostic of OS (p = 0.02). Instead N classification was not significantly predictive of OS (p = 0.10). High LNRs resulted in decreases in OS of approximately 40% within 6 months after surgery.

Conclusions

The LNR identifies patients with poor outcomes better than N classification. The lack of reliable LNR cutoffs compromises its utility in clinical practice.

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Proteomic Characterization of Senescent Laryngeal Adductor and Plantaris Hindlimb Muscles

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Objectives

The goals of this study were to 1) compare global protein expression in muscles of the larynx and hindlimb and 2) investigate differences in protein expression between aged and nonaged muscle using label-free global proteomic profiling methods.

Methods

Liquid chromatography-mass spectrometry (LC-MS/MS) analysis was performed on thyroarytenoid intrinsic laryngeal muscle and plantaris hindlimb muscle from 10 F344xBN F1 male rats (5 old and 5 young). Protein expression was compared and pathway enrichment analysis performed for each muscle type (larynx and limb) and age group (old and young muscle).

Results

Over 1,000 proteins were identified in common across both muscle types and age groups using LC-MS/MS analysis. Significant age-related differences were seen across 107 proteins in plantaris hindlimb and in 19 proteins in thyroarytenoid laryngeal muscle. Bioinformatic and enrichment analysis demonstrated protein differences between the hindlimb and larynx may relate to immune and stress redox responses and RNA repair.

Conclusion

There are clear differences in protein expressions between the laryngeal and hindlimb skeletal muscles. Initial analysis suggests differences between the two muscle groups may relate to stress responses and repair mechanisms. Age-related changes in the thyroarytenoid appear to be less obvious than in the plantaris. Further in-depth study is needed to elucidate how aging affects protein expression in the laryngeal muscles.

Level of Evidence

NA Laryngoscope, 2021

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A novel mouse model to evaluate neuropeptide Y‐mediated melanocyte pathology

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Abstract

Vitiligo is an autoimmune disease characterized by depigmented patches of skin due to loss of the pigment-producing melanocytes. No cure exists for vitiligo. The available treatments are inefficient for many patients, suggesting that universal treatment approaches may be inappropriate. Deeper understanding of the mechanistic basis for variability in vitiligo etiologies is necessary. Genetic mutations in neuropeptide Y (NPY), a widely distributed protein, are associated with increased NPY expression and increased susceptibility for vitiligo. NPY is also upregulated in the circulation and lesional skin of some vitiligo patients. However, the contributions of NPY to melanocyte pathology are not understood, and presently there are no models with which to investigate this possibility. In this study, we employed NPY-overexpressing mice to explore the role of NPY in melanocyte dysfunction. Our results show that NPY-overexpression induces progressive hair graying (depigmentation) due to p remature depletion of follicular melanocyte stem cells. Additionally, NPY transcripts and protein are elevated in the skin and melanocytes of these mice, respectively, suggesting that these effects may be mediated locally. Together, these results suggest that supraphysiological levels of NPY in the skin can induce melanocyte dysfunction, thus identifying this mouse line as a novel model to study NPY-mediated melanocyte pathology.

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Type 2 diabetes impairs vascular responsiveness to nitric oxide, but not the venoarteriolar reflex or post‐occlusive reactive hyperaemia in forearm skin

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Abstract

The venoarteriolar reflex (VAR) is a local mechanism by which vasoconstriction is mediated in response to venous congestion. This response may minimize tissue overperfusion, preventing capillary damage and edema. Post-occlusive reactive hyperaemia (PORH) is used to appraise microvascular function performed by a brief local arterial occlusion resulting in a subsequent rapid transient vasodilation. In the current study, we hypothesized that type 2 diabetes (T2D) attenuates VAR and PORH responses in forearm skin in vivo. In 11 healthy older adults (Control, 58±8 years) and 13 older adults with controlled T2D (62±10 years), cutaneous blood flow measured by laser-Doppler flowmetry was monitored following a 3-min venous occlusion of 45 mmHg that elicited the VAR, followed by a 3-min recovery period and then a 5-min arterial occlusion of 240 mmHg that induced PORH. Finally, sodium nitroprusside, a nitric oxide donor, was administered to induce maximum vasodilation. VAR and PORH variabl es were similar between groups. By contrast, maximal cutaneous blood flow induced by sodium nitroprusside was lower in the T2D group. Taken together, our observations indicate that T2D impairs vascular smooth muscle responsiveness to nitric oxide, but not VAR and PORH in forearm skin.

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Cellular reprogramming of diabetic foot ulcer fibroblasts triggers pro‐healing miRNA‐mediated epigenetic signature

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Abstract

Diabetic foot ulcers (DFUs), a prevalent complication of diabetes, constitute a major medical challenge with a critical need for development of cell-based therapies. We previously generated induced pluripotent stem cells (iPSCs) from dermal fibroblasts derived from the DFU patients, location-matched skin of diabetic patients and normal healthy donors and re-differentiated them into fibroblasts. To assess the epigenetic microRNA (miR) regulated changes triggered by cellular reprogramming, we performed miRs expression profiling. We found let-7c, miR-26b-5p, −29c-3p, −148a-3p, −196a-5p, −199b-5p and −374a-5p suppressed in iPSC-derived fibroblasts in vitro and in 3D dermis-like self-assembly tissue, whereas their corresponding targets involved in cellular migration were upregulated. Moreover, targets involved in organization of extracellular matrix were induced after fibroblast reprogramming. PLAT gene, the crucial fibrinolysis factor, was upregulated in iPSC-derived fibrobl asts and was confirmed as a direct target of miR-196a-5p. miR-197-3p and miR-331-3p were found upregulated specifically in iPSC-derived diabetic fibroblasts, while their targets CAV1 and CDKN3 were suppressed. CAV1, an important negative regulator of wound healing, was confirmed as a direct miR-197-3p target. Together, our findings demonstrate that iPSC reprogramming is an effective approach for erasing the diabetic non-healing miR-mediated epigenetic signature and promoting a pro-healing cellular phenotype.

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The involvement of translationally controlled tumor protein during lamb rumen epithelium development

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Via histochem

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Acta Histochem. 2021 Jun 8;123(5):151737. doi: 10.1016/j.acthis.2021.151737. Online ahead of print.

ABSTRACT

Early weaning is usually applied to improve the reproductive efficiency of sheep in mutton production, while the development of rumen is of vital importance for sheep weaning age. Translationally controlled tumor protein (TCTP) is a highly conserved protein which participates in multiple tissue and organ development. Thus, we hypothesized that TCTP was involved in shee p rumen development. Histological analyses of sheep rumen epithelium showed that the epithelium formed tough shaped papillae without growing from birth to day 15 of age, after which it rapidly developed to functional epithelia on day 45 of age. We then found TCTP expressed in stratum basale, stratum spinosum and stratum granulosum of rumen epithelium. TCTP protein expression remained at a relative low level from day 0 to day 15 of age, it then significantly increased on day 30 (p < 0.05) and gradually decreased until day 60. Furthermore, to explore the role of TCTP in sheep rumen and its regulation, we found the ratio of Ki67 positive cell in stratum basale cells followed the similar pattern as the expression of TCTP. We also found the ratio of acetate:propionate in rumen fluid decreased from day 30 to day 60 of age (p < 0.05). To conclude, our data indicated that TCTP participated in rumen papillae growth by promoting rumen stratum basale cell proliferation.

PMID:34116359 | DOI:10.1016/j.acthis.2021.151737

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Congenital Anomalies of the Ossicular Chain: Surgical and Audiological Outcomes

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Ann Otol Rhinol Laryngol. 2021 Jun 11:34894211025405. doi: 10.1177/00034894211025405. Online ahead of print.

ABSTRACT

OBJECTIVES: In this study, we aim to analyze audiometric outcomes of middle ear surgery in patients with congenital middle ear anomalies.

METHODS: In this single center retrospective cohort study, audiological outcomes were extracted from patient files. Patients with a congenital middle ear anomaly treated surgically in a tertiary referral center betwee n June 2015 and December 2020 were included. Pre- and postoperative short- and long-term audiometric data (at ≥3 and ≥10 months respectively) were compared to analyze hearing outcomes.

RESULTS: Eighteen ears (15 patients) were treated surgically with an exploratory tympanotomy. At short term follow up statistically significant improvements in air conduction thresholds and air-bone gaps were found. Hearing improved in 94.4% (17/18) of operated ears. Successful outcome, defined as an air-bone gap closure to within 20 dB after surgery, was reached in 44.4% (8/18). Serviceable hearing (air conduction ≤30 dB) was reached in 55.6% (10/18). Negative outcome (any significant deterioration in hearing) occurred in 1 patient: in this ear otitis media occurred during the postoperative course. At long term follow up, available for 50% of the cohort, hearing remained stable in 5 ears, improved in 1 ear and deteriorated in 3, all of which underwent revision surgery. Sensorineural heari ng loss due to surgery, or other complications, were not encountered.

CONCLUSION: middle ear surgery was found to be an effective treatment option to improve hearing in this cohort of patients with congenital middle ear anomalies. Surgical goals of obtained gain in air conduction thresholds and serviceable hearing levels were met by most patients without the occurrence of any iatrogenic sensorineural hearing loss.

PMID:34116598 | DOI:10.1177/00034894211025405

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Predictors of Improvement in Quality of Life When Treating Hypothyroidism

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Background. Primary hypothyroidism is characterized by reduced quality of life (QoL). Although thyrotropin (TSH) is utilized as the primary indicator of thyroid disease and treatment adequacy, no simple correlation between QoL and TSH has been shown. This study aimed to investigate changes in clinically relevant predictors during initiation of levothyroxine (L-T4) therapy and their ability to predict improvement in QoL. Method. Quality of life was measured in patients with newly diagnosed hypothyroidism, during the initial 12 months of L-T4 therapy, by the thyroid-related patient-reported outcome questionnaire, ThyPRO-39. The main outcome measures were the Composite QoL scale and the Tiredness and Emotional Susceptibility subscales (0–100, higher scores worse). Clinical variables (resting energ y expenditure (REE), body composition, thyroid function, L-T4 dose, and cognitive function tests) were evaluated as predictors of improvement in QoL by univariate and multiple regression analysis. Results. Thirty-seven hypothyroid patients with a baseline median TSH of 30 mU/l and a median QoL score of 29 were included. After twelve months of L-T4 treatment, the ThyPRO-39 QoL score had significantly improved to a median score of 14, while REE per kg fat-free mass (FFM) increased significantly from a mean of 26.5 to 28.7 kcal/day/kg (). Change in ThyPRO-39 was not associated with a change in REE/FFM (unstandardized coefficient (USC): 0.09 with confidence interval (CI): −1.93 to 2.11, ) but was positively predicted by baseline body mass index (BMI) (USC: 1.54 with CI: 0.59 to 2.49, (), without association with weight loss (USC: 0.33 with CI: −1.21 to 1.27, ).Conclusion. Improvement in QoL as measured by ThyPRO-39 after initiation of L-T4 therapy for hypothyroidism was not asso ciated with changes in REE. High baseline BMI, but not weight loss during therapy, was associated with improvement in QoL. This trail is registered with www.Clinicaltrials.gov (registration no. https://clinicaltrials.gov/ct2/show/NCT02891668).
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Prepancreatic common hepatic artery arising from superior mesenteric artery: an exceptional but important finding during pancreaticoduodenectomy

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Surg Radiol Anat. 2021 Jun 12. doi: 10.1007/s00276-021-02786-7. Online ahead of print.

ABSTRACT

PURPOSE: The hepato-mesenteric trunk is an extremely rare condition in which the common hepatic artery (CHA) originates from the superior mesenteric artery (SMA). Usually, CHA passes behind the head of the pancreas. A systematic review was performed to provide guidelines for the perioperative management of patients with this anatomical variation who underwent a pancreaticoduodenec tomy (PD). A case report was also included.

METHODS: A systematic search of the literature was conducted and the manuscript was structured following point-by-point the PRISMA guidelines. The risk of bias within individual studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist tools. Case report was structured according to the CARE guidelines.

RESULTS: After an initial selection of 141 titles, 9 articles were included in the study (n = 10 patients). A postoperative surgical complication which required a reintervention occurred only one time. In four patients, CHA had a posterior position relative to pancreas, while in three cases, it was anterior. The remaining three patients had an intrapancreatic course. The CHA was resected in two patients, with an end-to-end reconstruction or using the splenic artery stump. In only three patients, a preoperative multidisciplinary presentation was performed and in four cases, the CHA variation was not descr ibed by radiologists in formal CT-scan reports.

CONCLUSION: Although there are no definitive guidelines, improvements in the preoperative knowledge of such a rare anatomical variation may ensure better postoperative outcomes, avoiding intraoperative accidents and life-threatening postoperative complications.

PMID:34117902 | DOI:10.1007/s00276-021-02786-7

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Cortical Responses to Vowel Sequences in Awake and Anesthetized States: A Human Intracranial Electrophysiology Study

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Cereb Cortex. 2021 Jun 12:bhab168. doi: 10.1093/cercor/bhab168. Online ahead of print.

ABSTRACT

Elucidating neural signatures of sensory processing across consciousness states is a major focus in neuroscience. Noninvasive human studies using the general anesthetic propofol reveal differential effects on auditory cortical activity, with a greater impact on nonprimary and auditory-related areas than primary auditory cortex. This study used intracranial electroencephalography to examine cortical responses to vowel sequences during induction of general anesthesia with propofol. Subjects were adult neurosurgical patients with intracranial electrodes placed to identify epileptic foci. Data were collected before electrode removal surgery. Stimuli were vowel sequences presented in a target detection task during awake, sedated, and unresponsive states. Averaged evoked potentials (AEPs) and high gamma (70-150 Hz) power were measured in auditory, audito ry-related, and prefrontal cortex. In the awake state, AEPs were found throughout studied brain areas; high gamma activity was limited to canonical auditory cortex. Sedation led to a decrease in AEP magnitude. Upon LOC, there was a decrease in the superior temporal gyrus and adjacent auditory-related cortex and a further decrease in AEP magnitude in core auditory cortex, changes in the temporal structure and increased trial-to-trial variability of responses. The findings identify putative biomarkers of LOC and serve as a foundation for future investigations of altered sensory processing.

PMID:34117741 | DOI:10.1093/cercor/bhab168

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Pignat's vertical partial laryngectomy with crico-hyoido-epiglotto-plasty

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Eur Arch Otorhinolaryngol. 2021 Jun 11. doi: 10.1007/s00405-021-06858-7. Online ahead of print.

ABSTRACT

PURPOSE: Pignat's partial laryngectomy with crico-hyoido-epiglotto-plasty (CHEPL) is a vertical laryngectomy with resection of the anterior portion of the thyroid cartilage and reconstruction with a wires net and the subhyoid muscles. The aim of this retrospective study was to evaluate and analyze oncologic and functional outcomes in patients affected by laryngeal squamous cell carcinoma and treated with Pignat's partial laryngectomy.

METHODS: Seventy patients with cT1-cT3 glottic cancer were surgically treated with Pignat's technique.

EXCLUSION CRITERIA: invasion of posterior cricoid arch, more than 3 mm under glottis, of more than one arytenoid, of posterior portion of thyroid cartilage, of the suprahyoid epiglottis. Overall survival, disease free survival, rates of decannulation and enteral feeding were analyzed.

< p>RESULTS: 23 (32.9%) pT1, 37 (52.9%) pT2, 5 (7.1%) pT3, 5 (7.1%) pT4a, 64 (91.5%) pN0, 5 (7.1%) pN1, 1 (1.4%) pN2. Adjuvant treatment was administered to 13 patients (18.6%). All patients had tracheotomy. Five year OS and DFS were 81.66 and 77.95%, respectively. A statistically significant DFS difference was observed between early and late stages. Five year local control was 81.16%. Five year larynx preservation rate was 89.16%. Median decannulation time was 12 days. Median duration of enteral nutrition was 16 days. All patients achieved efficient phonation.

CONCLUSION: Pignat's partial laryngectomy with CHEPL can represent an alternative to horizontal supracricoid laryngectomy to achieve laryngeal preservation. Good oncologic and functional outcomes are possible as long as indications are followed.

PMID:34117535 | DOI:10.1007/s00405-021-06858-7

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