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Κυριακή 13 Ιουνίου 2021

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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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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Treatment of juvenile recurrent parotitis with irrigation therapy without anesthesia

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Eur Arch Otorhinolaryngol. 2021 Jun 12. doi: 10.1007/s00405-021-06928-w. Online ahead of print.

ABSTRACT

PURPOSE: No standardized treatment regimen exists for juvenile recurrent parotitis (JRP). The investigators hypothesized that irrigation with saline only without local anesthesia will be an effective and beneficial option.

METHODS: Using a retrospective study design, a series of children with typical symptoms of JRP who were treated with at least one irrigation therapy were evaluated. This treatment consisted of irrigation of the affected gland with 3-10 ml saline solution without any type of anesthesia. The outcome variables were patient/parent satisfaction, frequency and duration of acute JRP episodes, and the need for antibiotics before and after irrigation therapy.

RESULTS: The case series was composed of six boys aged 3.3-7.7 years who experienced one to eight sessions of irrigation therapy. The period of follow-up was 9-64 months. We observed a total resolution of symptoms in two children and an improvement in the other four. No relevant side effects were seen.

CONCLUSION: Our results suggest that irrigation therapy is a reasonable, simple, and minimally invasive treatment alternative for JRP. In contrast to sialendoscopy or sialography, there is no need for general anesthesia or radiation exposure.

PMID:34117898 | DOI:10.1007/s00405-021-06928-w

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Swallowing Exercise During Head and Neck Cancer Treatment: Results of a Randomized Trial

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Dysphagia. 2021 Jun 11. doi: 10.1007/s00455-021-10320-5. Online ahead of print.

ABSTRACT

The diagnosis and treatment of head and neck cancer (HNC) can have substantial impact on swallowing function, nutritional balance, physical function and quality of life (QoL). Early initiated swallowing exercises are hypothesized to improve swallowing function in HNC patients. The aim was to investigate the effects of swallowing exercises and progressive resistance training (PRT) during radioth erapy on swallowing function, physical function and QoL in patients with pharynx-, larynx-, oral cavity cancer or unknown primary compared to usual care. In a multi-centre RCT participants were assigned to (a) twice-weekly PRT and daily swallowing exercises throughout treatment or (b) usual care. Outcomes were measured at end of treatment and 2, 6 and 12 months after. Primary outcome was penetration aspiration score (PAS). Data were analysed on an "intention-to-treat" basis by GEE logistic regression model, linear mixed effects model and cox regression. Of 371 invited HNC patients, 240 (65%) enrolled. Five participants were excluded. At 12 months follow-up, 59 (25%) participants were lost. Analyses showed significant effect on mouth opening, QoL, depression and anxiety at 12 months when comparing intervention to non-active controls. The trial found no effect on swallowing safety in HNC undergoing radiotherapy, but several positive effects were found on secondary outcomes when compar ing to non-active controls. The intervention period may have been too short, and the real difference between groups is too small. Nevertheless, the need to identify long-lasting intervention to slow down or avoid functional deteriorations is ever more crucial as the surviving HNC population is growing.

PMID:34117531 | DOI:10.1007/s00455-021-10320-5

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Bleeding complications in patients with squamous cell carcinoma of the head and neck

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Abstract

Hemorrhage in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) may be attributed to chemotherapy and local tumor irradiation. Evidence of the relationship between hemorrhage in R/M HNSCC and targeted therapies, including epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) inhibitors, or immune checkpoint inhibitors, is limited. We aimed to identify epidemiological and clinical data related to the occurrence of hemorrhage in R/M HNSCC and to explore its relationship with various therapies. We describe information obtained from literature searches as well as data extracted from a commercial database and a database from the author's institution (Istituto Nazionale dei Tumori of Milan). Evidence suggests that most bleeding events in R/M HNSCC are minor. Clinical trial safety data do not identify a causal association between hemorrhage and anti-EGFR agents or immune checkpoint inhibitors. In contrast, anti-VEGF agents are associated with increased, and often severe/fatal, hemorrhagic complications.

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