New Findings
What is the central question of this study?
The prevalence of sedentary behaviour in the workplace and increased daily sitting time have been associated with the development of ...cardiovascular disease; however, studies investigating the impact of sitting on vascular function remain limited.
What is the main finding and its importance?
We demonstrate that there is a marked vulnerability of the vasculature in the lower and upper limbs to prolonged sitting and highlight the importance of physical activity in restoring vascular function in a limb‐specific manner.
Sedentary behaviour in the workplace and increased daily sitting time are on the rise; however, studies investigating the impact of sitting on vascular function remain limited. Herein, we hypothesized that 6 h of uninterrupted sitting would impair limb micro‐ and macrovascular dilator function and that this impairment could be improved with a bout of walking. Resting blood flow, reactive hyperaemia to 5 min cuff occlusion (microvascular reactivity) and associated flow‐mediated dilatation (FMD; macrovascular reactivity) were assessed in popliteal and brachial arteries of young men at baseline (Pre Sit) and after 6 h of uninterrupted sitting (Post Sit). Measures were then repeated after a 10 min walk (∼1000 steps). Sitting resulted in a marked reduction of resting popliteal artery mean blood flow and mean shear rate (6 h mean shear rate, −52 ± 8 s−1 versus Pre Sit, P < 0.05). Interestingly, reductions were also found in the brachial artery (6 h mean shear rate, −169 ± 41 s−1 versus Pre Sit, P < 0.05). Likewise, after 6 h of sitting, cuff‐induced reactive hyperaemia was reduced in both the lower leg (−43 ± 7% versus Pre Sit, P < 0.05) and forearm (−31 ± 11% versus Pre Sit, P < 0.05). In contrast, popliteal but not brachial artery FMD was blunted with sitting. Notably, lower leg reactive hyperaemia and FMD were restored after walking. Collectively, these data suggest that prolonged sitting markedly reduces lower leg micro‐ and macrovascular dilator function, but these impairments can be fully normalized with a short bout of walking. In contrast, upper arm microvascular reactivity is selectively impaired with prolonged sitting, and walking does not influence this effect.
RATIONALE:Remote ischemic preconditioning (rIPC) with short episodes of ischemia/reperfusion (I/R) of an organ remote from the heart is a powerful approach to protect against myocardial I/R injury. ...The signal transduction pathways for the cross talk between the remote site and the heart remain unclear in detail.
OBJECTIVE:To elucidate the role of circulating nitrite in cardioprotection by rIPC.
METHODS AND RESULTS:Mice were subjected to 4 cycles of no-flow ischemia with subsequent reactive hyperemia within the femoral region and underwent in vivo myocardial I/R (30 minutes/5 minutes or 24 hours). The mouse experiments were conducted using genetic and pharmacological approaches. Shear stress–dependent stimulation of endothelial nitric oxide synthase within the femoral artery during reactive hyperemia yielded substantial release of nitric oxide, subsequently oxidized to nitrite and transferred humorally to the myocardium. Within the heart, reduction of nitrite to nitric oxide by cardiac myoglobin and subsequent S-nitrosation of mitochondrial membrane proteins reduced mitochondrial respiration, reactive oxygen species formation, and myocardial infarct size. Pharmacological and genetic inhibition of nitric oxide/nitrite generation by endothelial nitric oxide synthase at the remote site or nitrite bioactivation by myoglobin within the target organ abrogated the cardioprotection by rIPC. Transfer experiments of plasma from healthy volunteers subjected to rIPC of the arm identified plasma nitrite as a cardioprotective agent in isolated Langendorff mouse heart preparations exposed to I/R.
CONCLUSIONS:Circulating nitrite derived from shear stress–dependent stimulation of endothelial nitric oxide synthase at the remote site of rIPC contributes to cardioprotection during I/R.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT01259739.
The PET tracer (11)C-deuterium-L-deprenyl ((11)C-DED) has been used to visualize activated astrocytes in vivo in patients with Alzheimer disease (AD). In this multitracer PET study, early-phase ...(11)C-DED and (11)C-Pittsburgh compound B ((11)C-PiB) (eDED and ePiB, respectively) were compared as surrogate markers of brain perfusion, and the extent to which (11)C-DED binding is influenced by brain perfusion was investigated.
(11)C-DED, (11)C-PiB, and (18)F-FDG dynamic PET scans were obtained in age-matched groups comprising AD patients (n = 8), patients with mild cognitive impairment (n = 17), and healthy controls (n = 16). A modified reference Patlak model was used to quantify (11)C-DED binding. A simplified reference tissue model was applied to both (11)C-DED and (11)C-PiB to measure brain perfusion relative to the cerebellar gray matter (R1) and binding potentials. (11)C-PiB retention and (18)F-FDG uptake were also quantified as target-to-pons SUV ratios in 12 regions of interest (ROIs).
The strongest within-subject correlations with the corresponding R1 values (R1,DED and R1,PiB, respectively) and with (18)F-FDG uptake were obtained when the eDED and ePiB PET data were measured 1-4 min after injection. The optimum eDED/ePiB intervals also showed strong, significant ROI-based intersubject Pearson correlations with R1,DED/R1,PiB and with (18)F-FDG uptake, whereas (11)C-DED binding was largely independent of brain perfusion, as measured by eDED. Corresponding voxelwise correlations confirmed the ROI-based results. Temporoparietal eDED or ePiB brain perfusion measurements were highly discriminative between patient and control groups, with discriminative ability statistically comparable to that of temporoparietal (18)F-FDG glucose metabolism. Hypometabolism extended over wider regions than hypoperfusion in patient groups compared with controls.
The 1- to 4-min early-frame intervals of (11)C-DED or (11)C-PiB are suitable surrogate measures for brain perfusion. (11)C-DED binding is independent of brain perfusion, and thus (11)C-DED PET can provide information on both functional (brain perfusion) and pathologic (astrocytosis) aspects from a single PET scan. In comparison with glucose metabolism, early-phase (11)C-DED and (11)C-PiB perfusion appear to provide complementary rather than redundant information.
Object
Expanded endonasal approaches have dramatically changed how skull base surgery is performed, and nasoseptal flap (NSF) has significantly improved skull base reconstruction. However, challenges ...remain when the pterygopalatine artery is invaded by tumors; when it must be sacrificed to approach the lateral sphenoidal recess; when late‐occurrence leak occurs in the sella after transsphenoidal surgery; and also when the leak is on the posterior wall of the frontal sinus, which is too distant for NSF to reach. This article describes a septal floor rotational flap pedicled on ethmoidal arteries for endoscopic skull base reconstruction in certain cases.
Study Design
Case series.
Method
In this article, we retrospectively review a series of 19 patients who underwent skull base reconstruction with a septal floor rotational flap pedicled on the ethmoidal arteries.
Result
All 19 flaps, including the anterior and posterior artery pedicled flaps, survived without significant complications, and no postoperative cerebrospinal fluid leak occurred during follow‐up.
Conclusion
Ethmoidal arteries pedicled septal floor rotational flap, with their strong blood supply and large coverage area, are ideal replacements for NSF. These flaps are qualified in locations ranging from the posterior wall of the frontal sinus to the lateral sphenoidal recess and in cases ranging from tumor invading the pterygopalatine fossa to sellar late‐occurred leak after transsphenoidal surgery.
Level of Evidence
4 Laryngoscope, 129:2696–2701, 2019
In guinea pigs, choroidal thickness (ChT) and choroidal blood perfusion (ChBP) simultaneously decrease in experimental myopia, and both increase during recovery. However, the causal relationship ...between ChBP and myopia requires further investigation. In this study, we examined the changes of ChBP with three different antimyopia treatments. We also actively increased ChBP to examine the direct effect on myopia development in guinea pigs.
Experiment 1: Guinea pigs wore occluders on the right eye for two weeks to induce form-deprivation myopia (FDM). Simultaneously they received daily antimyopia treatments: peribulbar injections of atropine or apomorphine or exposure to intense light. Experiment 2: The vasodilator prazosin was injected daily into the form-deprivation eyes to increase ChBP during the two-week induction of FDM. Other FDM animals received appropriate control treatments. Changes in refraction, axial length, ChBP, ChT, and hypoxia-labeled pimonidazole adducts in the sclera were measured.
The antimyopia treatments atropine, apomorphine, and intense light all significantly inhibited myopia development and the decrease in ChBP. The treatments also reduced scleral hypoxia, as indicated by the decrease in hypoxic signals. Furthermore, actively increasing ChBP with prazosin inhibited the progression of myopia, as well as the increase in axial length and scleral hypoxia.
Our data strongly indicate that increased ChBP attenuates scleral hypoxia, and thereby inhibits the development of myopia. Thus ChBP may be a promising target for myopia retardation. As such, it can serve as an immediate predictor of myopia development as well as a long-term marker of it.
Background
Recently major developments in video imaging have been achieved: among these, the use of high definition and 3D imaging systems, and more recently indocyanine green (ICG) fluorescence ...imaging are emerging as major contributions to intraoperative decision making during surgical procedures. The aim of this study was to present our experience with different laparoscopic procedures using ICG fluorescence imaging.
Patients and methods
108 ICG-enhanced fluorescence-guided laparoscopic procedures were performed: 52 laparoscopic cholecystectomies, 38 colorectal resections, 8 living-donor nephrectomies, 1 laparoscopic kidney autotransplantation, 3 inguino-iliac/obturator lymph node dissections for melanoma, and 6 miscellanea procedures. Visualization of structures was provided by a high definition stereoscopic camera connected to a 30° 10 mm scope equipped with a specific lens and light source emitting both visible and near infra-red (NIR) light (KARL STORZ GmbH & Co. KG, Tuttlingen, Germany). After injection of ICG, the system projected high-resolution NIR real-time images of blood flow in vessels and organs as well as highlighted biliary excretion .
Results
No intraoperataive or injection-related adverse effects were reported, and the biliary/vascular anatomy was always clearly identified. The imaging system provided invaluable information to conduct a safe cholecystectomy and ensure adequate vascular supply for colectomy, nephrectomy, or find lymph nodes. There were no bile duct injuries or anastomotic leaks.
Conclusions
In our experience, the ICG fluorescence imaging system seems to be simple, safe, and useful. The technique may well become a standard in the near future in view of its different diagnostic and oncological capabilities. Larger studies and more specific evaluations are needed to confirm its role and to address its disadvantages.
Background
The anti-VEGF antibody, bevacizumab, is standard treatment for patients with recurrent glioblastoma. In this setting, traditional anatomic MRI methods such as post-contrast T1-weighted and ...T2-weighted imaging are proving unreliable for monitoring response. Here we evaluate the prognostic significance of pre- and posttreatment relative cerebral blood volume (rCBV) derived from dynamic susceptibility contrast MRI to predict response to bevacizumab.
Methods
Thirty-six participants with recurrent high-grade gliomas who underwent rCBV imaging 60 days before and 20–60 days after starting bevacizumab treatment were enrolled. Tumor regions of interest (ROIs) were determined from deltaT1 maps computed from the difference between standardized post and precontrast T1-weighted images. Both pre- and posttreatment rCBV maps were corrected for leakage and standardized (stdRCBV) to a consistent intensity scale. The Kaplan–Meier method was used to determine if either the pre- or post-bevacizumab stdRCBV within the tumor ROI was predictive of overall survival (OS) or progression free survival (PFS).
Results
The OS was significantly longer if either the pre- (380d vs 175d; P=.0024) or posttreatment stdRCBV (340d vs 186d; P = .0065) was <4400. The posttreatment stdRCBV was also predictive of PFS (167d vs 78d; P = .0006). When the stdRCBV values were both above versus both below threshold, the OS was significantly worse (100.5d vs 395d; P < .0001). With a 32.5% decrease in stdRCBV, the risk of death was reduced by about 68% but increased by 140% with a 29% increase in stdRCBV.
Conclusions
Standardized rCBV is predictive of OS and PFS in patients with recurrent high-grade brain tumor treated with bevacizumab.
AbstractBackgroundPerfusion plays an important role in anastomotic healing. Indocyanine-green fluorescence angiogram allows objective bowel perfusion assessment. This study aimed to investigate the ...impact of perfusion assessment on intraoperative decision during left-sided colorectal resections. MethodThis was a prospective, single-centre, observational study recruiting patients with left-sided colorectal resections. Perfusion of bowel segment was assessed with ICG fluorescence angiogram prior to resection and anastomosis intra-operatively. The planned transection site and the actual transection site after perfusion assessment were compared. The decision for diversion stoma was also evaluated. Results110 patients with cancer of the sigmoid colon (29.1%) and rectum (70.9%) were recruited. Total mesorectal excision was performed in 51.8% of patients. The transection site was revised in 34.5% of cases: 30.9% more proximally and 3.6% more distally. The median distance between the intended and actual transection sites was 2 cm (range 1–17 cm). A proximal revision in the transection site was more likely seen in rectal cancers (p = 0.036, OR 3.58, 95% CI 1.09–11.78) and relatively under-perfused left colon (p = 0.036, OR 1.01, 95% CI 1.01–1.02). Three (2.7%) patients were spared from a diversion stoma. The overall anastomotic leakage rate was 5.5%. ConclusionICG fluorescence angiogram altered operative decisions in a significant proportion of cases. The impact on transection site was more pronounced in patients with rectal cancers and those with relatively under-perfused colon.
The study was aimed at assessing the influence of pelvic congestion syndrome (PCS) on the clinical manifestations of chronic venous disease (CVD) of the lower extremities in patients with concomitant ...varicose veins of the pelvis and lower extremities.
We examined clinically and with duplex ultrasound 30 women with varicose veins of the lower extremity only (VVLE) and another 45 women with VVLE and concomitant varicose veins of the pelvis (VVP) causing symptoms of the pelvic congestion syndrome (PCS).
All patients had chronic venous disease (CVD) of class C2 (n = 47) or C3 (n = 28) according to the CEAP classification. All patients underwent duplex ultrasound (DUS) of the lower extremities and pelvis. Based on the clinical examination and DUS findings, the patients were allocated into two groups: group 1 (n = 30 patients with isolated VVLE without the signs of PCS and pelvic veins lesions) and group 2 (n = 45 patients with concomitant PCS, VVP and VVLE). The rates and severity of varicose, pain, and edema syndromes, and leg heaviness were assessed.
The patients of the group 2 had significantly more severe clinical manifestations of CVD, 4 times higher risk of leg pain (odds ratio OR 4.23; 95% CI 1.57–11.39), 7 times higher risk of leg edema (OR 7.42; 95% CI 2.23–24.78), 5 times higher risk of leg heaviness (OR 5.3; 95% CI 1.85–15.07), and in general 2 times more severe varicose veins, compared with the group 1.
The PCS is associated with an increase in the incidence and severity of the CVD symptoms.
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