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High local recurrence rates with aggressive disease remain the main concern in oral cancer survival. Use of a translational device using fluorescence visualization (FV) approved by the US Food and Drug Administration and Health Canada, has shown a marked reduction in the 3-year local recurrence rate of high-grade oral lesions in a single-center observational study.
To determine whether FV- guided surgery can improve local control rates in the treatment of in situ or T1 to T2 category oral squamous cell carcinoma (OSCC).
A multicenter randomized clinical trial was conducted in a surgical setting. A total of 457 patients were enrolled between January 18, 2010, and April 30, 2015. Data analysis of the intention-to-treat population was performed from April 3, 2019, to March 20, 2020. Patients with histologically confirmed high-grade dysplasia/carcinoma in situ or T1 to T2 category OSCC were randomized to receive traditional peroral surgery or FV-guided surgery.
Fluorescence visualization during surgery.
and overall survival (41/227 [18.1%] vs 38/216 [17.6%]) were also similar between groups. No adverse events were judged to be related to the intervention.
In this randomized clinical trial, FV-guided surgery did not improve local control rates in the treatment of patients with in situ or T1 to T2 category oral cancer. Under a controlled environment, FV-guided surgery did not have an evident effect in reduction of local recurrence for localized OSCC. This result suggests that attention be directed to strategies other than improving definitions of nonapparent disease at clinical margins to identify the sources of local recurrence.
ClinicalTrial.gov Identifier NCT01039298.
ClinicalTrial.gov Identifier NCT01039298.
Osteoporosis and anemia are among the most common diseases in the aging population with an increasing prevalence worldwide.
As the bone-derived hormone fibroblast growth factor 23 (FGF-23) was recently reported to regulate erythropoiesis, we examined age-related associations between hemoglobin levels and bone quality, bone turnover, and FGF-23 concentrations.
We used data from more than 5000 adult subjects who participated in the population-based cohorts of the Study of Health in Pomerania (SHIP and SHIP-Trend). Bone quality was assessed by quantitative ultrasound at the heel, bone turnover by measurement of carboxy-terminal telopeptide of type I collagen (CTX), and intact amino-terminal propeptide of type I procollagen (P1NP) serum concentrations, respectively. Anemia was defined as hemoglobin <13 g/dL in men and <12 g/dL in women. Carboxy-terminal FGF-23 levels were measured in plasma in a subset of 852 subjects.
Anemic subjects had poorer bone quality, higher fracture risk, and lower serum levels of P1NP than nonanemic individuals. Linear regression models revealed positive associations between hemoglobin and bone quality in subjects aged 40 or above and inverse associations with CTX in subjects aged 60 or above. Hemoglobin and FGF-23 concentrations were inversely associated, while FGF-23 was not related to bone quality or turnover.
Our data corroborate a close link between FGF-23 and anemia, which is related to poor bone quality in elderly people. We observed no direct association of FGF-23 with bone parameters. Further studies are needed clarifying the role of FGF-23 on bone and red blood cell production.
Mertk inhibitor corroborate a close link between FGF-23 and anemia, which is related to poor bone quality in elderly people. We observed no direct association of FGF-23 with bone parameters. Further studies are needed clarifying the role of FGF-23 on bone and red blood cell production.
The current coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented needs for invasive ventilation, with 10% to 15% of intubated patients subsequently requiring tracheotomy.
To assess the complications, safety, and timing of tracheotomy performed for critically ill patients with COVID-19.
This prospective cohort study assessed consecutive patients admitted to the intensive care unit (ICU) who had COVID-19 that required tracheotomy. Patients were recruited from March 16 to April 10, 2020, at a tertiary referral center.
A surgical tracheotomy was performed for all patients following recommended criteria for use of personal protective equipment (PPE).
The number of subthyroid operations, the tracheal entrance protocol, and use of PPE. Infections among the surgeons were monitored weekly by reverse-transcriptase polymerase chain reaction of nasopharyngeal swab samples. Short-term complications, weaning, and the association of timing of tracheotomy (early [≤10 days] vs late [>10 days]) wiThe reduction of invasive ventilatory support was achieved at the expense of the pretracheotomy period.
In this cohort study, with the use of a standardized protocol aimed at minimizing COVID-19 risks, bedside open tracheotomy was a safe procedure for patients and surgeons, with minimal complications. #link# Timing of tracheotomy may be important in reducing time of invasive mechanical ventilation, with potential implications to intensive care unit availability during the COVID-19 pandemic.
In this cohort study, with the use of a standardized protocol aimed at minimizing COVID-19 risks, bedside open tracheotomy was a safe procedure for patients and surgeons, with minimal complications. Timing of tracheotomy may be important in reducing time of invasive mechanical ventilation, with potential implications to intensive care unit availability during the COVID-19 pandemic.
The exact mechanisms that trigger the onset of puberty are not well known. Adipomyokines are postulated to stimulate the central neural network. In the present study, we investigated irisin levels in girls with central precocious puberty (CPP), slowly progressing precocious puberty (SPPP), or premature thelarche (PT); we also studied prepubertal girls and to determine if this adipomyokine could be used as a marker in this context.
A total of 94 girls including 33 with CPP, 31 with precocious puberty (PP) variants (SPPP or PT), and 30 healthy controls were enrolled to the study. The mean irisin levels were compared between groups. The bivariate correlations of irisin levels with clinical and laboratory parameters were assessed. Multivariate linear regression analysis was performed to determine independent predictive factors of irisin levels.
Irisin levels were higher in the CPP group compared with the other groups (CPP group 723.25 ± 62.35 ng/mL; PP variants group 529.60 ± 39.66 ng/mL; and control group 325.03 ± 27.53 ng/mL) (P < 0.001). Irisin levels were positively correlated with body mass index standard deviation scores (BMI-SDS), height-SDS, weight-SDS, bone age, uterus long axis, ovary size, baseline FSH and LH, and peak LH levels. link2 Multivariate linear regression analysis revealed that irisin levels had the strongest correlation with peak LH. The other independent predictive factor of irisin levels was BMI-SDS.
The mean irisin levels were higher in patients with CPP compared with other groups. The results of this study imply that increased irisin levels may be used as a marker of CPP provided that these findings are confirmed in larger prospective studies.
The mean irisin levels were higher in patients with CPP compared with other groups. The results of this study imply that increased irisin levels may be used as a marker of CPP provided that these findings are confirmed in larger prospective studies.Ryanodine receptors are responsible for the massive release of calcium from the sarcoplasmic reticulum that triggers heart muscle contraction. link3 Maurocalcin (MCa) is a 33 amino acid peptide toxin known to target skeletal ryanodine receptor. We investigated the effect of MCa and its analog MCaE12A on isolated cardiac ryanodine receptor (RyR2), and showed that they increase RyR2 sensitivity to cytoplasmic calcium concentrations promoting channel opening and decreases its sensitivity to inhibiting calcium concentrations. By measuring intracellular Ca2+ transients, calcium sparks and contraction on cardiomyocytes isolated from adult rats or differentiated from human-induced pluripotent stem cells, we demonstrated that MCaE12A passively penetrates cardiomyocytes and promotes the abnormal opening of RyR2. We also investigated the effect of MCaE12A on the pacemaker activity of sinus node cells from different mice lines and showed that, MCaE12A improves pacemaker activity of sinus node cells obtained from mice lacking L-type Cav1.3 channel, or following selective pharmacologic inhibition of calcium influx via Cav1.3. Our results identify MCaE12A as a high-affinity modulator of RyR2 and make it an important tool for RyR2 structure-to-function studies as well as for manipulating Ca2+ homeostasis and dynamic of cardiac cells.
Coronavirus disease 2019 (COVID-19) has been recognized as a pandemic by the World Health Organization. Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can also infect tissues besides the respiratory system, such as the ocular tissues, remains unclear.
To determine whether SARS-CoV-2 exists intracellularly in the ocular tissues of a patient previously infected with COVID-19.
This case study analyzed a patient previously infected with COVID-19 who had an acute glaucoma attack during her rehabilitation. Plasma samples and tissue specimens, including ones from the conjunctiva, anterior lens capsular, trabecular meshwork, and iris, were collected during phacoemulsification and trabeculectomy surgery. Specimens from another patient who had glaucoma but not COVID-19 were used as a negative control.
Specimens were analyzed using hematoxylin-eosin staining. The nucleocapsid protein antigen of SARS-CoV-2 was measured in the conjunctiva, trabecular meshwork, and iris using immunofluorescences in addition to the respiratory system.Heart failure (HF) is associated with impaired L-arginine transport. In the present study, we tested the hypothesis that augmented L-arginine transport prevents the loss of kidney function in HF. Renal function was assessed in wildtype mice (WT), transgenic mice with HF (dilated cardiomyopathy, DCM) and double transgenic mice (double transgenic mice with DCM and CAT-1 overexpression, HFCAT-1) with HF and endothelial-specific overexpression of the predominant L-arginine transporter, cationic amino acid transporter-1 (CAT-1) (n=4-8/group). Cardiac function was assessed via echocardiography and left ventricular catheterisation. Renal function was assessed via quantification of albuminuria and creatinine clearance. Plasma nitrate and nitrite levels together with renal fibrosis and inflammatory markers were also quantified at study end. Albumin/creatinine ratio was two-fold greater in DCM mice than in WT mice (P=0.002), and tubulointerstitial and glomerular fibrosis were approximately eight- and three-fold greater, respectively, in DCM mice than in WT mice (P≤0.02). Critically, urinary albumin/creatinine ratio and tubulointerstitial and glomerular fibrosis were less in HFCAT-1 mice than in DCM mice (P less then 0.05). Renal CAT-1 expression and plasma nitrate and nitrite levels were less in DCM mice compared with WT (P≤0.03) but was greater in HFCAT-1 mice than in DCM mice (P≤0.009). Renal expression of IL-10 was less in DCM mice compared with WT (P less then 0.001) but was greater in HFCAT-1 mice compared with DCM mice (P=0.02). Our data provide direct evidence that augmented L-arginine transport prevents renal fibrosis, inflammation and loss of kidney function in HF.
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