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Background: This study tested the hypothesis that training reduces resting sympathetic activity and improves baroreflex control in both hypertensive and normotensive men but reduces blood pressure only in hypertensive men.Methods: Middle-aged/older un-medicated stage-1 hypertensive males (mean age 55±3 yrs; n=13) and normotensive controls (mean age 60±5 yrs; n=12) participated in 8 weeks of supervised high-intensity interval spinning training. Before and after training, muscle sympathetic nerve activity (MSNA) and blood pressure were measured at rest and during a sympatho-excitatory cold pressor test (CPT). Based on the measurements, baroreceptor sensitivity and baroreceptor threshold were calculated.Results: Resting MSNA and baroreceptor sensitivity were similar for the hypertensive and the normotensive groups. Training lowered MSNA (ppp>0.05) alter the MSNA or blood pressure response to CPT or increase baroreceptor sensitivity but reduced (pConclusion: The dissociation between the training induced changes in resting MSNA, lack of change in baroreflex sensitivity and the change in blood pressure, suggests that MSNA is not a main cause of the blood pressure reduction with exercise training in un-medicated middle-aged/older men.

Baroreflex resetting permits sympathetic long-term facilitation (sLTF) following hypoxia; however, baroreflex control of action potential (AP) clusters and AP recruitment patterns facilitating sLTF is unknown. We hypothesized that baroreflex resetting of arterial pressure operating points (OPs) of AP clusters and recruitment of large-amplitude APs would mediate sLTF following hypoxia. Eight men (age: 24 (3) years; body mass index: 24 (3) kg/m

Myocardial oxygen delivery is primarily regulated through changes in vascular tone to match increased metabolic demands. In males, activation of the muscle metaboreflex during acute isocapnic hypoxia results in paradoxical coronary vasoconstriction. Whether coronary blood velocity is reduced by metaboreflex activation following travel and/or adaptation to high altitude is unknown. This study determined if the response of the coronary vasculature to muscle metaboreflex activation at low altitude differs from acute (1/2 days) and prolonged (8/9 days) high altitude. Healthy males (

Introduction: This study aimed to examine the effect of breakages and re-introduction into cold chain on the rocuronium bromide compound. Rocuronium bromide is frequently used in routine theatre lists and plays a vital role in modified rapid sequence induction and intubation for emergency patients who have contraindications to the primarily used muscle relaxant, succinylcholine. With the current practice of removing the drug from, and then reintroducing it into the cold chain, unpredictable clinical effects, including delayed onset of action and shortened duration of action have been observed. This may pose significant risks to the patient. Methods: Rocuronium bromide was subjected to different clinically applicable storage and temperature scenarios, after which the compound was analysed for integrity and quantities of the active compound, including detection of possible degradation products, by mass spectrometry, and compared to cold chain control samples. Results: There were no significant differences between any of the temperature exposure groups (18 °C or 24 °C) or between single or double exposures at these temperatures. No statistically significant difference could be demonstrated between the two control groups (cold chain preserved and room temperature controlled) with testing done at weeks one and six. However, week twelve analysis revealed a statistically significant result which translates to a 26 μg/ml difference, which clinically would have no effect. Substantial results were obtained with a secondary exposure to air; which lead to a 20% decrease in rocuronium concentration (p = 0.02). Conclusion: Practice should be adapted by keeping careful documentation as to when cold-chain was broken, and when the recommended 12 week period will lapse. Vial sharing as a standard is not recommended. If small quantities are repeatedly withdrawn from the vial during a prolonged case, the unused contents should be discarded after eight hours.

Post-hypoxia sympathoexcitation does not elicit corresponding changes in vascular tone, suggesting diminished sympathetic signalling. Blunted sympathetic transduction following acute hypoxia, however, has not been confirmed and the effects of hypoxia on the sympathetic transduction of mean arterial pressure (MAP) as a function of action potential (AP) activity is unknown. We hypothesized that MAP changes would be blunted during acute hypoxia but restored in recovery and asynchronous APs would elicit smaller MAP changes than synchronous APs. Seven healthy males (age: 24 (3) years; BMI: 25 (3) kg/m

Subpopulations of muscle sympathetic single units can be inhibited during mild sympathoexcitatory stress. We demonstrate that rhythmic handgrip exercise and isocapnic hypoxia, when matched by multiunit sympathoexcitation, induce similar proportions of single-unit inhibition, highlighting that heterogeneous single-unit response patterns are related to the level of sympathoexcitation independent of the stressor type. Interestingly, only 47% of single units behaved with concordant response patterns between stressors, suggesting the potential for functional specificity within the postganglionic neuronal pool.

PURPOSE In normotensive patients with obstructive sleep apnea (OSA), the muscle sympathetic nerve activity (MSNA) response to exercise is increased while metaboreflex control of MSNA is decreased. We tested the hypotheses that acute intermittent hypercapnic hypoxia (IHH) in males free from OSA and associated comorbidities would augment the MSNA response to exercise but attenuate the change in MSNA during metaboreflex activation. METHODS Thirteen healthy males (age = 24 ± 4 yr) were exposed to 40 min of IHH. Before and after IHH, the pressor response to exercise was studied during 2 min of isometric handgrip exercise (at 30% maximal voluntary contraction), whereas the metaboreflex was studied during 4 min of postexercise circulatory occlusion (PECO). Mean arterial pressure (MAP), heart rate (HR), and fibular MSNA were recorded continuously. MSNA was quantified as burst frequency (BF) and total activity (TA). Mixed effects linear models were used to compare the exercise pressor and metaboreflex before and after IHH. RESULTS As expected, IHH led to significant increases in MSNA BF, TA, and MAP at baseline and throughout exercise and PECO. However, during handgrip exercise, the change from baseline in MAP, HR, MSNA BF, and TA was similar before and after IHH (All P > 0.31). During PECO, the change from baseline in MSNA BF and TA was similar after IHH, whereas the change from baseline in MAP (Δ14 mm Hg, 95% CI = 7-19, vs Δ16 mm Hg, 95% CI = 10-21; P < 0.01) was modestly increased. CONCLUSION After acute IHH, MSNA response to handgrip exercise and metaboreflex activation were preserved in healthy young males despite overall increases in resting MSNA and MAP. Chronic IHH and comorbidities often associated with OSA may be required to modulate the exercise pressor reflex and metaboreflex.

Contains fulltext : 229287.pdf (Publisher’s version ) (Open Access) BACKGROUND AND PURPOSE: A matched comparison of external beam radiotherapy (EBRT) versus brachytherapy recently demonstrated that EBRT appears at least as effective for palliating dysphagia in patients with incurable esophageal cancer. The aim of this analysis was to compare patient-reported outcomes (PROs) after EBRT versus brachytherapy. MATERIALS AND METHODS: In a multicenter prospective cohort study, patients with incurable esophageal cancer requiring palliation of dysphagia were included to undergo EBRT (20 Gy in 5 fractions). This EBRT cohort was compared to the single-dose 12 Gy brachytherapy cohort of the previously reported SIREC-trial. Propensity score matching was applied to adjust for baseline imbalances. The primary endpoint of dysphagia improvement was reported previously. PROs were secondary outcomes and assessed at baseline and 3 months after treatment using EORTC QLQ-C30 and QLQ-OES18 questionnaires. RESULTS: A total of 115 enrolled EBRT patients and 93 brachytherapy patients were eligible. After matching, 69 well-balanced pairs remained. At follow-up, significant deteriorations in functioning (i.e. physical, role, social), pain, appetite loss, and trouble with taste were observed after brachytherapy. In the EBRT group, such deterioration was observed only for role functioning, while significant improvements in trouble with eating and pain were found. Between-group comparison showed mostly comparable PRO changes, but significantly favored EBRT with regard to nausea, vomiting, pain, and appetite loss. CONCLUSION: Short course EBRT results in similar or better PROs at 3 months after treatment compared to single-dose brachytherapy for the palliation of malignant dysphagia. These findings further support its use and inclusion in clinical practice guidelines.

Hyperoxic blood has a small stabilizing effect on agitated saline contrast compared with mixed venous blood, lending support to studies that show the reversal of exercise-induced blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) with hyperoxia. These data support the possible presence of a local O2-dependent regulatory mechanism within the pulmonary vasculature that may play a role in Q̇IPAVA regulation.

Key points Ventilatory long-term facilitation (vLTF) refers to respiratory neuroplasticity that develops following intermittent hypoxia in both healthy and clinical populations. A sustained hypercapnic background is argued to be required for full vLTF expression in humans. We determined whether acute intermittent hypercapnic hypoxia elicits vLTF during isocapnic-normoxic recovery in healthy males and females. We further assessed whether tonic peripheral chemoreflex drive is necessary and contributes to the expression of vLTF. Following 40-minutes of intermittent hypercapnic hypoxia, minute ventilation was increased throughout 50-minutes of isocapnic-normoxic recovery. Inhibition of peripheral chemoreflex drive with hyperoxia attenuated the magnitude of vLTF. Males and females achieve vLTF through different respiratory recruitment patterns. Abstract Ventilatory long-term facilitation (vLTF) refers to respiratory neuroplasticity that manifests as increased minute ventilation (VI ) following intermittent hypoxia. In humans, hypercapnia sustained throughout intermittent hypoxia and recovery is considered necessary for vLTF expression. We examined whether acute intermittent hypercapnic hypoxia (IHH) induces vLTF, and if peripheral chemoreflex drive contributes to vLTF throughout isocapnic-normoxic recovery. In 19 individuals (9 females, age: 22±3, mean±SD), measurements of tidal volume (VT ), breathing frequency (fB ), VI , and end-tidal gases (PET O2 and PET CO2 ), were made at baseline, during IHH and 50-minutes of recovery. Totalling 40-minutes, IHH included 1-minute intervals of 40-s hypercapnic hypoxia (target PET O2 = 50 mmHg and PET CO2 = +4 mmHg above baseline) and 20-s normoxia. During baseline and recovery, dynamic end-tidal forcing maintained resting PET O2 and PET CO2 and delivered 1-minute of hyperoxia (PET O2 : 355±7 mmHg) every 5-minutes. The depression in VI during hyperoxia was considered an index of peripheral chemoreflex drive. Throughout recovery VI was increased 4.6±3.7 l/min from baseline (P

NEW FINDINGS What is the central question of this study? Coronary blood flow in healthy humans is controlled by both local metabolic signaling and adrenergic activity, but whether the integration of these signals during acute hypoxia and adrenergic activation differs between sexes is unknown. What are the main findings and its importance? Both males and females exhibit an increase in coronary blood velocity in response to acute hypoxia, a response that is constrained by adrenergic stimulation in males but not females. These findings suggest that coronary blood flow control differs between males and females. ABSTRACT Coronary hyperemia is mediated through multiple signaling pathways, including local metabolic messengers and adrenergic stimulation. This study aimed to determine whether the coronary vascular response to adrenergic stressors is different between sexes in normoxia and hypoxia. Young, healthy participants (n = 32; 16F) underwent three-randomized trials of isometric handgrip exercise followed by post-exercise circulatory occlusion (PECO) to activate the muscle metaboreflex. End-tidal PO2 was controlled at (1) normoxic levels throughout the trial, (2) 50 mmHg for the duration of the trial (hypoxia trial), or (3) 50 mmHg only during PECO (mixed trial). Mean left anterior descending coronary artery velocity (LADVmean ; transthoracic Doppler echocardiography), heart rate and blood pressure were assessed at baseline and during PECO. In normoxia, there was no change in LADVmean or cardiac workload induced by PECO in males and females. Acute hypoxia increased baseline LADVmean to a greater extent in males compared with females (P < 0.05), despite a similar increase in cardiac workload. The change in LADVmean induced by PECO was similar between sexes in normoxia (P = 0.31), greater in males during the mixed trial (male: 12.8 (7.7) cm/s vs female: 8.1 (6.3) cm/s; P = 0.02) and reduced in males but not females in acute hypoxia (male: -4.8 (4.5) cm/s vs female: 0.8 (6.2) cm/s; P = 0.006). In summary, sex differences in the coronary vasodilatory response to hypoxia were observed, and metaboreflex activation during hypoxia caused a paradoxical reduction in coronary blood velocity in males but not females. This article is protected by copyright. All rights reserved.

Background and Aims To further optimize endoscopic stent placement, an esophageal fully covered self-expandable metal stent with a through-the-scope (TTS) delivery system was designed, providing direct endoscopic control during stent placement. The aim of the study was to assess the feasibility and safety of a TTS stent approach for palliation of malignant dysphagia. Methods This multicenter prospective feasibility study included patients with malignant dysphagia undergoing stent placement. The primary outcome was technical success of TTS stent placement. Secondary outcomes included functional outcome, adverse events, and survival. Patients were prospectively evaluated at days 14 and 28, and monthly thereafter, until death or stent removal. Results In total, 33 stents were placed in 32 patients. TTS stent placement was feasible in 30 (91%) procedures. In the other 3 procedures (9%), no large-channel endoscope could be introduced because of patient discomfort. In 10 (33%) TTS procedures, technical success was achieved because no fluoroscopy and/or guidewire was used, whereas in 20 (67%) TTS procedures, placement was supported by a guidewire (n = 9), or fluoroscopy and a guidewire (n = 11). After 2 weeks, dysphagia scores had improved in 24 (86%) patients. Median dysphagia-free time was 32 days (interquartile range [IQR], 17–76 days). In 20 (63%) patients, 29 serious adverse events (SAEs) occurred. Recurrent dysphagia occurred in 13 (41%) patients due to migration (n = 5), tissue overgrowth (n = 4), and stent deformation (n = 4). Other SAEs included significant retrosternal pain (n = 4), hemorrhage (n = 2), and esophageal perforation (n = 1). No patient died from a stent-related cause. Median survival was 42 days (IQR, 28–91 days). Conclusion Placement of an esophageal TTS stent was feasible in most of the patients with malignant dysphagia. However, stent placement was associated with a relatively high adverse event rate, and in more than one-third of patients, stent placement still required fluoroscopy, which limited optimal benefit of the TTS approach. (Clinical trial registration number: NCT03269903.)

NEW FINDINGS What is the central question of this study? Vascular compliance importantly contributes to the regulation of cerebral perfusion and complex mechanisms are known to influence compliance of a vascular bed: while vasodilatation mediates changes in vascular resistance, does it also affect compliance, particularly in the cerebral vasculature? What is the main finding and its importance? Cerebral vasodilatation, elicited by hypercapnia and sodium nitroglycerin administration, reduced cerebrovascular compliance by approximately 26% from baseline. This study provides new insight into mechanisms mediating cerebrovascular compliance. ABSTRACT Changes in vascular resistance and vascular compliance contribute to the regulation of cerebral perfusion. While changes in vascular resistance are known to be mediated by vasodilatation, the mechanisms contributing to changes in vascular compliance are complex. In particular, whether vasodilatation affects compliance of the vasculature within the cranium remains unknown. Therefore, the present study examined the impact of two vasodilatation pathways on cerebrovascular compliance in humans. Fifteen young, healthy adults (26 ± 5 years, seven females) completed two protocols: (i) sublingual sodium nitroglycerin (SNG; 0.4 mg) and (ii) hypercapnia (5-6% carbon dioxide gas mixture for 4 min). Blood pressure waveforms (finger photoplethysmography) and middle cerebral artery blood velocity waveforms (transcranial Doppler ultrasound) were input into a modified Windkessel model and an index of cerebrovascular compliance (Ci) was calculated. During the SNG protocol, Ci decreased 24 ± 17% from baseline ((5.0 ± 2.3) × 10-4 cm s-1 mmHg-1 ) to minute 10 ((3.6 ± 1.2) × 10-4 cm s-1 mmHg-1 ; P = 0.009). During the hypercapnia protocol, Ci decreased 28 ± 9% from baseline ((4.4 ± 1.9) × 10-4 cm s-1 mmHg-1 ) to minute 4 ((3.1 ± 1.4) × 10-4 cm s-1 mmHg-1 ; P

In childhood, clinical presentation of intes- tinal polyps is variable. Painless rectal red blood loss is the most common presenting sign. Most polyps are sporadic, isolated and benign. However, it is important to correctly identify exceptions. Rare inherited polyposis syndromes need to be recognized because of their increased risk of intestinal and extra-intestinal malignancies. Furthermore, a correct diagnosis and treatment of rare gastro-intestinal malignancies is crucial.Between 2016 and 2018 we encountered 4 different types of intestinal polyps. A database search was performed and patient files were checked for clinical manifestations and histo- pathology. Literature was searched to recapitulate red flags for these syndromes, probability of underlying genetic disorders and diagnostic criteria.Between 2016 and 2018, 28 patients presented at the Ghent University Hospital with 30 juvenile polyps. Furthermore, we diagnosed juvenile polyposis syndrome, Li Fraumeni syndrome and familial adenomatous polyposis (FAP) in 1 patient each, whilst 2 FAP patients were in follow-up. Each of these diagnoses has a different lifetime risk of (extra)-intestinal malignancy and requires a different approach and follow-up. Histopathology and genetic testing play an important role in identifying these syndromes in pediatric patients.Although most intestinal polyps in childhood are benign juvenile polyps that require no follow-up, rare inherited syndromes should be considered and correctly diagnosed since adequate follow-up is necessary to reduce morbidity and mortality from both gastrointestinal and extraintestinal complications and malignancies.

The utility of transthoracic saline contrast echocardiography (TTSCE) to assess blood flow through intrapulmonary arteriovenous anastomoses (Q̇

We report dengue virus (DENV) infection in two Dutch tourists who visited Département Var, southern France, in July and August 2020. As some autochthonous dengue cases have occurred in Europe in recent years, awareness among physicians and public health experts about possible intermittent presence of DENV in southern Europe is important to minimise delay in diagnosis and treatment. Quick diagnosis can lead to timely action to contain the spread of vector-borne diseases and minimise transmission.

This case study reports the efferent muscle sympathetic nerve activity (MSNA) discharge patterns during a sinus pause observed during a maximal end-expiratory apnea in a young healthy male (age = 26 yr). During a 15.3-s end-expiratory apnea following a bout of intermittent hypercapnic hypoxia, we observed a 5.2-s (R-R interval) sinus pause and integrated MSNA recording, demonstrating a square-wave discharge pattern atypical of sharp MSNA burst peaks entrained to cardiac cycles or during preventricular contractions. This abnormal MSNA discharge pattern was observed again during a follow-up experiment, where an end-expiratory apnea at baseline resulted in pronounced bradycardia (R-R intervals >2.5-s) but failed to reproduce the 5.2-s sinus pause. Action potential (AP) discharge patterns during MSNA bursts were detected using a continuous wavelet transform approach. AP discharge increased by 300% during the end-expiratory apnea with 5.2-s sinus pause compared with baseline and involved increased firing (i.e., rate-coding) of AP clusters (bins of AP with similar morphology) already present during baseline and pronounced recruitment of larger-amplitude AP clusters not present at baseline. Large-amplitude AP clusters continued to discharge during sinus pause. In summary, we show MSNA discharge during sinus pause and pronounced bradycardia during end-expiratory apnea, which demonstrates a square-wave discharge with recruitment of latent larger-amplitude AP clusters. The MSNA discharge was terminated before systole following sinus pause potentially through an inhibitory influence of inspiration, or cardiac mechanoreceptor feedback causing burst termination. NEW & NOTEWORTHY We characterize the occurrence of a square-wave discharge pattern of efferent muscle sympathetic nerve activity during a sinus pause in a young healthy male. This discharge pattern comprised large recruited action potential clusters undetected at baseline that continuously discharged during the sinus pause. Notably, this discharge pattern was still contained within a single cardiac cycle.

New findings What is the central question of this study? What is the impact of oxygen on the circulatory responses to an isocapnic cold pressor test (CPT) in lowlanders and Andean highlanders? What is the main finding and its importance? Overall, the circulatory responses to an isocapnic CPT were largely unaltered with acute normobaric hypoxia and chronic hypobaric hypoxia exposure in lowlanders. However, the relationship between mean arterial pressure and common carotid artery diameter was dampened under hypoxic conditions. Furthermore, there were no differences in the circulatory responses to the CPT between lowlanders and Andean highlanders with lifelong exposure to high-altitude. Abstract The impact of oxygen on the circulatory responses to a cold pressor test (CPT) in lowlanders and Andean highlanders remains unknown. We hypothesized: 1) in lowlanders, acute normobaric and hypobaric hypoxia would attenuate the common carotid artery (CCA) diameter response to the CPT compared to normobaric normoxia; 2) Andean highlanders would exhibit a greater CCA diameter response compared to lowlanders; and, 3) a positive relationship between CCA diameter and blood pressure in response to the CPT would be present in both lowlanders and highlanders. Healthy lowlanders (n = 13) and Andean highlanders (n = 8) were recruited and conducted an isocapnic CPT, which consisted of a 3-minute foot immersion into 0-1 °C water. Blood pressure (finger photoplethysmography) and CCA diameter and blood flow (Duplex ultrasound) were continuously recorded. The CPT was conducted in lowlanders at sea-level under isocapnic normoxic and hypoxic conditions, and after 10 days of acclimatization to 4300 m (Cerro de Pasco, Peru) under hypoxic and hyperoxic conditions. Andean highlanders were tested at rest at high-altitude. The main findings were: 1) in lowlanders, normobaric, but not hypobaric hypoxia, elevated CCA reactivity to the CPT; 2) no differences in response to CPT was observed between lowlanders and highlanders, and; 3) while hypobaric hypoxemia reduced the relationship between CCA diameter and blood pressure compared to normobaric normoxia (P = 0.132), hypobaric hyperoxia improved this relationship (P = 0.012), and no relationship was observed in Andean highlanders (P = 0.261). These data demonstrate that the circulatory responses to a CPT are modified by oxygen in lowlanders, but unaltered with lifelong hypoxic exposure. This article is protected by copyright. All rights reserved.

Purpose Clinical evidence regarding optimal radiation dose for palliation of dysphagia from esophageal cancer is generally lacking. In an effort to investigate optimal radiation dose, we assessed 2 different radiation schedules for palliation of dysphagia. Methods and Materials We performed a multicenter, retrospective study comparing low-dose radiation therapy (LR: 5 x 4 Gy external beam radiation therapy [EBRT]) with high-dose radiation therapy (HR: 10 x 3 Gy EBRT and 12-Gy single-dose intraluminal brachytherapy) for palliation of dysphagia in patients with inoperable or metastasized esophageal cancer. Primary outcome was improvement of dysphagia at 6 weeks after start of radiation therapy. Additional outcomes were persistent and recurrent dysphagia during patients' remaining life, severe adverse events, and survival. Results In total, 292 patients (LR, n=117; HR, n=175) were included in this study. After matching, 144 patients (72 in each group) were compared. Improvement of dysphagia at 6 weeks was achieved in 50% of patients after LR and in 66% after HR (P = .071). Persistent or recurrent dysphagia occurred in 64% of patients after LR and in 42% after HR (P = .012). No difference in the rate of severe adverse events was found (P = .889). Median survival was 88 days (95% confidence interval, 64-112) after LR and 177 days (95% confidence interval, 131-223) after HR (P Conclusions This study shows that both LR and HR were well tolerated and effective in short-term relief of dysphagia in patients with inoperable or metastasized esophageal cancer. HR was associated with better long-term relief of dysphagia compared with LR. Our findings suggest that HR could be considered for patients with a longer life expectancy, but prospective studies are required.

In resting spontaneously breathing men, the present study observed that sympathetic baroreflex sensitivity (BRS) was higher during low versus high lung volumes but not different between inspiration and expiration. High- but not low-lung volume BRS was negatively associated with resting muscle sympathetic nerve activity (MSNA). Acute intermittent hypercapnic hypoxia increased resting MSNA and diastolic blood pressure, without altering within-breath BRS. These findings provide novel insight into mechanisms controlling within-breath modulation of MSNA in humans.

Contains fulltext : 193353.pdf (Publisher’s version ) (Open Access) OPINION STATEMENT: PURPOSE OF REVIEW: Esophageal stents are used in clinical practice for endoscopic treatment of a wide variety of esophageal diseases and conditions. This review provides key principles and a literature update on the utility and limitations of esophageal stenting in clinical practice. RECENT FINDINGS: Indications for esophageal stenting can be subdivided into two groups. The first group consists of patients with malignant or benign dysphagia, in which an esophageal stent restores luminal patency. In the past years, temporary stent placement has increasingly been used in the therapeutic management of refractory benign esophageal strictures. When endoscopic repeated bougie dilation and other endoscopic treatment modalities have failed, an esophageal stent could be considered. Based on the literature, a fully covered self-expandable metal stent may be the preferred choice for the treatment of both malignant and benign dysphagia. The second group consists of patients with leakage from the esophageal lumen into the surrounding tissue. Esophageal leakage can be subdivided into three forms, benign esophageal perforations (iatrogenic and spontaneous), anastomotic leakage after reconstructive esophageal surgery, and fistula. In a carefully selected group of patients, a covered esophageal stent may be used for sealing off the leakage, thereby preventing further contamination of the tissue surrounding the defect. The past few years, several validated prediction tools have been developed that may assist clinicians in the selection of patients eligible for esophageal stent placement. Based on retrospective studies and expert opinion, a partially or fully covered self-expandable metal stent may have a role in treatment of esophageal leakage. Research do date supports the utilization of esophageal stents for the treatment of malignant or benign dysphagia and esophageal leakage.

Rapidly progressive hip disease (RDHD) is a rare condition of the hip joint, causing destruction of the femoral head. The pathogenesis is unknown. The disease is self-limiting, there is no treatment to stop the disease. Hip arthroplasty is a successful way to relieve pain and restore function. We present a case where both hips were involved and analysed. A favourable result was obtained by bilateral total hip arthroplasty.

Contains fulltext : 220092.pdf (Publisher’s version ) (Open Access) Background: The Dutch guidelines for esophageal and gastro-esophageal junction (GEJ) cancer recommend discussion of patients by a multidisciplinary tumor board (MDT). Despite this recommendation, one previous study in the Netherlands suggested that therapeutic guidance was missing for palliative care of patients with esophageal cancer. The aim of the current study was therefore to assess the impact of an MDT discussion on initial palliative treatment and outcome of patients with esophageal or GEJ cancer.Material and methods: The population-based Netherlands Cancer Registry was used to identify patients treated for esophageal or GEJ cancer with palliative intent between 2010 and 2017 in 7 hospitals. We compared patients discussed by the MDT with patients not discussed by the MDT in a multivariate analysis. Primary outcome was type of initial palliative treatment. Secondary outcome was overall survival.Results: A total of 389/948 (41%) patients with esophageal or GEJ cancer were discussed by the MDT before initial palliative treatment. MDT discussion compared to non-MDT discussion was associated with more patients treated with palliative intent external beam radiotherapy (38% vs. 21%, OR 2.7 [95% CI 1.8-3.9]) and systemic therapy (30% vs. 23%, OR 1.6 [95% CI 1.0-2.5]), and fewer patients treated with stent placement (4% vs. 12%, OR 0.3 [95% CI 0.1-0.6]) and best supportive care alone (12% vs. 33%, OR 0.2 [95% CI 0.1-0.3]). MDT discussion was also associated with improved survival (169 days vs. 107 days, HR 1.3 [95% CI 1.1-1.6]).Conclusion: Our study shows that MDT discussion of patients with esophageal or GEJ cancer resulted in more patients treated with initial palliative radiotherapy and chemotherapy compared with patients not discussed by the MDT. Moreover, MDT discussion may have a positive effect on survival, highlighting the importance of MDT meetings at all stages of treatment.

Endoscopic dilation (ED) is still the mainstay of therapeutic management of benign esophageal strictures (BESs). This study aimed to establish risk factors for refractory BESs and assess long-term clinical outcomes of ED.We performed a retrospective study in 891 patients who underwent ED from 2003 to 2018 for BESs. We searched electronic medical records in 6 tertiary care centers in the Netherlands for data on clinical outcome of ED. Median follow-up was 39 months. The primary endpoint was risk factors for refractory BESs, defined as factors associated with an increased number of ED sessions during follow-up. Secondary endpoints were time from first to last ED session and adverse events.Dilation up to 13 to 15 mm was associated with a higher number of ED sessions than dilation up to 16 to 18 mm (5.0 vs 4.1; hazard ratio [HR], 1.4; P = .001). Compared with peptic strictures, anastomotic (4.9 vs 3.6; HR, 2.1; P .001), radiation (5.0 vs 3.6; HR, 3.0; P .001), caustic (7.2 vs 3.6; HR, 2.7; P .001), and postendotherapy (3.9 vs 3.6; HR, 1.8; P = .005) strictures were associated with a higher number of ED sessions. After 1 year of follow-up, the proportions of patients who remained free of ED was 75% in anastomotic, 71% in radiation, 70% in peptic, 83% in postendotherapy, and 62% in caustic strictures. Esophageal perforation occurred in 23 ED sessions (.4%) in 22 patients (2.4%).More than 60% of patients with BESs remain free of ED after 1 year of follow-up. Because dilation up to 16 to 18 mm diameter was associated with fewer ED sessions during follow-up, we suggest that clinicians should consider dilation up to at least 16 mm to reduce the number of ED sessions in these patients.

Background: The impact of cardiorespiratory comorbidity on operative outcomes after esophagectomy remains controversial. This study investigated the effect of cardiorespiratory comorbidity on postoperative complications for patients treated for esophageal or gastroesophageal junction cancer. Patients and Methods: A European multicenter cohort study from five high-volume esophageal cancer centers including patients treated between 2010 and 2017 was conducted. The effect of cardiorespiratory comorbidity and respiratory function upon postoperative outcomes was assessed. Results: In total 1590 patients from five centers were included; 274 (17.2%) had respiratory comorbidity, and 468 (29.4%) had cardiac comorbidity. Respiratory comorbidity was associated with increased risk of overall postoperative complications, anastomotic leak, pulmonary complications, pneumonia, increased Clavien–Dindo score, and critical care and hospital length of stay. After neoadjuvant chemoradiotherapy, respiratory comorbidity was associated with increased risk of anastomotic leak [odds ratio (OR) 1.83, 95% confidence interval (CI) 1.11–3.04], pneumonia (OR 1.65, 95% CI 1.10–2.47), and any pulmonary complication (OR 1.52, 95% CI 1.04–2.22), an effect which was not observed following neoadjuvant chemotherapy or surgery alone. Cardiac comorbidity was associated with increased risk of cardiovascular and pulmonary complications, respiratory failure, and Clavien–Dindo score ≥ IIIa. Among all patients, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio > 70% was associated with reduced risk of overall postoperative complications, cardiovascular complications, atrial fibrillation, pulmonary complications, and pneumonia. Conclusions: The results of this study suggest that cardiorespiratory comorbidity and impaired pulmonary function are associated with increased risk of postoperative complications after esophagectomy performed in high-volume European centers. Given the observed interaction with neoadjuvant approach, these data indicate a potentially modifiable index of perioperative risk.

Empirical spatial air pollution models have been applied extensively to assess exposure in epidemiological studies with increasingly sophisticated and complex statistical algorithms beyond ordinary linear regression. However, different algorithms have rarely been compared in terms of their predictive ability. This study compared 16 algorithms to predict annual average fine particle (PM2.5) and nitrogen dioxide (NO2) concentrations across Europe. The evaluated algorithms included linear stepwise regression, regularization techniques and machine learning methods. Air pollution models were developed based on the 2010 routine monitoring data from the AIRBASE dataset maintained by the European Environmental Agency (543 sites for PM2.5 and 2399 sites for NO2), using satellite observations, dispersion model estimates and land use variables as predictors. We compared the models by performing five-fold cross-validation (CV) and by external validation (EV) using annual average concentrations measured at 416 (PM2.5) and 1396 sites (NO2) from the ESCAPE study. We further assessed the correlations between predictions by each pair of algorithms at the ESCAPE sites. For PM2.5, the models performed similarly across algorithms with a mean CV R2 of 0.59 and a mean EV R2 of 0.53. Generalized boosted machine, random forest and bagging performed best (CV R2~0.63; EV R2 0.58–0.61), while backward stepwise linear regression, support vector regression and artificial neural network performed less well (CV R2 0.48–0.57; EV R2 0.39–0.46). Most of the PM2.5 model predictions at ESCAPE sites were highly correlated (R2 > 0.85, with the exception of predictions from the artificial neural network). For NO2, the models performed even more similarly across different algorithms, with CV R2s ranging from 0.57 to 0.62, and EV R2s ranging from 0.49 to 0.51. The predicted concentrations from all algorithms at ESCAPE sites were highly correlated (R2 > 0.9). For both pollutants, biases were low for all models except the artificial neural network. Dispersion model estimates and satellite observations were two of the most important predictors for PM2.5 models whilst dispersion model estimates and traffic variables were most important for NO2 models in all algorithms that allow assessment of the importance of variables. Different statistical algorithms performed similarly when modelling spatial variation in annual average air pollution concentrations using a large number of training sites. © 2019

When esophageal leakage is suspected, diagnostic work-up usually starts with endoscopy followed by CT of the thorax. Clinicians should consider esophageal leakage a clinical emergency as early diagnosis and treatment are associated with improved outcome. Upon diagnosis, acute therapeutic management in a specialized center with appropriate multidisciplinary infrastructure and expertise is indicated as innovative endoscopic treatment options have become reasonable alternatives to invasive surgical interventions. Promising endoscopic treatment options include esophageal stent placement, endoscopic vacuum therapy, and over-the-scope clip placement. In effort to evaluate the current literature, a systematic literature search was performed on studies reporting clinical outcome of patients treated with these endoscopic treatment options for benign esophageal perforations and anastomotic leakage. The systematic search yielded 15 studies (932 patients) discussing stent placement, 14 studies (295 patients) discussing endoscopic vacuum therapy, and 8 studies (41 patients) discussing over-the-scope clip placement. Clinical success was achieved in the majority of all patients. However, the studies predominantly consisted of small single-center retrospective case series. Careful selection of patients is therefore recommended when considering endoscopic therapy for esophageal leakage. Furthermore, clinical tools may aid in predicting patients’ prognosis and selection of patients that could benefit from endoscopic therapy. In the future, randomized studies comparing available endoscopic treatment options are needed to guide treatment choice for patients with esophageal leakage in daily clinical practice.

Acetazolamide, a carbonic anhydrase (CA) inhibitor used clinically and to prevent acute mountain sickness, worsens skeletal muscle fatigue in animals and humans. In animals, methazolamide, a methylated analog of acetazolamide and an equally potent CA inhibitor, reportedly exacerbates fatigue less than acetazolamide. Accordingly, we sought to determine, in humans, if methazolamide would attenuate diaphragm and dorsiflexor fatigue compared with acetazolamide. Healthy men (dorsiflexor: n = 12; diaphragm: n = 7) performed fatiguing exercise on three occasions, after ingesting acetazolamide (250 mg three times a day) and then in random order, methazolamide (100 mg twice a day) or placebo for 48 h. For both muscles, subjects exercised at a fixed intensity until exhaustion on acetazolamide, with subsequent iso-time and -workload trials. Diaphragm exercise was performed using a threshold-loading device, while dorsiflexor exercise was isometric. Neuromuscular function was determined pre- and postexercise by potentiated transdiaphragmatic twitch pressure and dorsiflexor torque in response to stimulation of the phrenic and fibular nerve, respectively. Diaphragm contractility 3–10 min postexercise was impaired more for acetazolamide than methazolamide or placebo (82 ± 10, 87 ± 9, and 91 ± 8% of pre-exercise value; P < 0.05). Similarly, dorsiflexor fatigue was greater for acetazolamide than methazolamide (mean twitch torque of 61 ± 11 vs. 57 ± 13% of baseline, P < 0.05). In normoxia, methazolamide leads to less neuromuscular fatigue than acetazolamide, indicating a possible benefit for clinical use or in the prophylaxis of acute mountain sickness. NEW & NOTEWORTHY Acetazolamide, a carbonic anhydrase inhibitor, may worsen diaphragm and locomotor muscle fatigue after exercise; whereas, in animals, methazolamide does not impair diaphragm function. Compared with both methazolamide and the placebo, acetazolamide significantly compromised dorsiflexor function at rest and after exhaustive exercise. Similarly, diaphragm function was most compromised on acetazolamide followed by methazolamide and placebo. Methazolamide may be preferable over acetazolamide for clinical use and altitude illness prophylaxis to avoid skeletal muscle dysfunction.

It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial Po2 and Pco2 or if coronary vascular responses are the result of concomitant increases in myocardial O2 consumption/demand ([Formula: see text]). We hypothesized that the coronary vascular response to Po2 and Pco2 would be attenuated in healthy men when [Formula: see text] was attenuated with β1-adrenergic receptor blockade. Healthy men (age: 25 ± 1 yr, n = 11) received intravenous esmolol (β1-adrenergic receptor antagonist) or volume-matched saline in a double-blind, randomized crossover study and were exposed to poikilocapnic hypoxia, isocapnic hypoxia, and hypercapnic hypoxia. Measurements made at baseline and after 5 min of steady state at each gas manipulation included left anterior descending coronary blood velocity (LADV; Doppler echocardiography), heart rate, and arterial blood pressure. LADV values at the end of each hypoxic condition were compared between esmolol and placebo. The rate-pressure product (RPP) and left ventricular mechanical energy (MELV) were calculated as indexes of [Formula: see text]. All gas manipulations augmented RPP, MELV, and LADV, but only RPP and MELV were attenuated (4–18%) after β1-adrenergic receptor blockade ( P < 0.05). Despite attenuated RPP and MELV responses, β1-adrenergic receptor blockade did not attenuate the mean LADV vasodilatory response compared with placebo during poikilocapnic hypoxia (29.4 ± 2.2 vs. 27.3 ± 1.6 cm/s) and isocapnic hypoxia (29.5 ± 1.5 vs. 30.3 ± 2.2 cm/s). Hypercapnic hypoxia elicited a feedforward coronary dilation that was blocked by β1-adrenergic receptor blockade. These results indicate a direct influence of arterial Po2 on coronary vascular regulation that is independent of [Formula: see text]. NEW & NOTEWORTHY In humans, arterial hypoxemia led to an increase in epicardial coronary artery blood velocity. β1-Adrenergic receptor blockade did not diminish the hypoxemic coronary response despite reduced myocardial O2 demand. These data indicate hypoxemia can regulate coronary blood flow independent of myocardial O2 consumption. A plateau in the mean left anterior descending coronary artery blood velocity-rate-pressure product relationship suggested β1-adrenergic receptor-mediated, feedforward epicardial coronary artery dilation. In addition, we observed a synergistic effect of Po2 and Pco2 during hypercapnic hypoxia.

Item does not contain fulltext Palliation of dysphagia is the cornerstone of palliative treatment in patients with incurable oesophageal cancer. Available palliative options for dysphagia are oesophageal stent placement and radiotherapy. In general, oesophageal stent placement is the preferred therapeutic option in patients with a relatively poor prognosis because of its rapid relief of dysphagia. Regardless of ongoing technical developments, recurrence of dysphagia and stent-related complications are still occurring. For patients with a relatively good prognosis, intra-luminal brachytherapy is advised because of its sustained palliation of dysphagia. Due to limited availability of intra-luminal brachytherapy in clinical practice, fractionated external beam radiation therapy is commonly applied as an alternative. Selection of the optimal palliative approach for patients remains however challenging as conclusive high-quality evidence is limited. Moreover, with the introduction of new palliative treatment options (e.g. palliative chemotherapeutic and radiotherapeutic options) and the concurrent change of patient characteristics, supporting evidence from large randomised studies is warranted.

Fractional differentiation has adequate use for investigating real world scenarios related to geological formations associated with elasticity, heterogeneity, viscoelasticity, and the memory effect. Since groundwater systems exist in these geological formations, modelling groundwater recharge as a real world scenario is a challenging task to do because existing recharge estimation methods are governed by linear equations which make use of constant field parameters. This is inadequate because in reality these parameters are a function of both space and time. This study therefore concentrates on modifying the recharge equation governing the EARTH model, by application of the Eton approach. Accordingly, this paper presents a modified equation which is non-linear, and accounts for parameters in a way that it is a function of both space and time. To be more specific, herein, recharge and drainage resistance which are parameters within the equation, became a function of both space and time. Additionally, the study entailed solving the non-linear equation using an iterative method as well as numerical solutions by means of the Crank-Nicolson scheme. The numerical solutions were used alongside the Riemann-Liouville, Caputo-Fabrizio, and Atangana-Baleanu derivatives, so that account was taken for elasticity, heterogeneity, viscoelasticity, and the memory effect. In essence, this paper presents a more adequate model for recharge estimation.

The use of stable isotope ratios of deuterium (δD) and oxygen (δ18O) together with major ion data can indicate the origins and movement of surface water and groundwater. During this investigation, hydrochemical and stable environmental isotope sampling were used to determine the interaction between the Karoo aquifer and the Witwatersrand aquifer. It was evident that shallower groundwater samples taken from the Karoo aquifer were affected by annual precipitation and had a short residence time, since their isotopic signature was very close to that of rainfall. By contrast, rainfall events had not recharged the Witwatersrand aquifer and had not significantly contributed to the isotopic fingerprint of the deeper aquifer samples. The Karoo aquifer is generally enriched in both δ18O and δD; the deeper Witwatersrand aquifer is more depleted in δ18O and δD. This is explained by their different intake histories and travelling periods. The results also indicate that there is interaction between the Karoo and Witwatersrand aquifer, both where coal mining is present and where it is not.

We put into exercise a comparatively innovative analytical modus operandi, the homotopy decomposition method (HDM), for solving a system of nonlinear partial differential equations arising in an attractor one-dimensional Keller-Segel dynamics system. Numerical solutions are given and some properties show evidence of biologically practical reliance on the parameter values. The reliability of HDM and the reduction in computations give HDM a wider applicability.

In Mpumalanga Province, South Africa, an underground coal mine lies above areas of a gold mine and there are concerns that preferential flow paths might connect the two mines, allowing flow from the coal mine into the gold mine. There is also a risk that subsidence associated with the coal mining will damage existing geohydrological barriers between the shallow Karoo aquifer where the coal mining takes place and the deeper Witwatersrand aquifer where the gold is mined. Damage to these geohydrological barriers could increase groundwater influx from the surface (gold mine slimes dams), as well as from the Karoo aquifer, into the Witwatersrand aquifer. Hydro-chemical sampling was used to determine interaction between the two aquifers. Certain high risk areas for potential interaction were identified after considering factors such as the depth and areas of mining, the location of tailings storage facilities, and preferential pathways.

Reducing the work of breathing during exercise improves locomotor muscle blood flow and reduces diaphragm and locomotor muscle fatigue and is thought to be the result of a sympathetically mediated reflex. AIM The aim of this study was to assess muscle sympathetic nerve activity (MSNA) when the work of breathing is experimentally lowered during dynamic exercise. METHODS Healthy subjects (n = 12; age = 29 ± 9 years) performed semi-recumbent cycling trials at 40%, 60%, and 80% of peak workload. Exercise trials consisted of spontaneous breathing, reduced work of breathing (proportional assist ventilator), followed by further spontaneous breathing (post-ventilator). MSNA was recorded from the median nerve. RESULTS There was no difference in work of breathing between PAV and post-PAV at 40% peak work. At 60% peak work, the ventilator significantly (P V ˙ O 2 (2.4 ± 0.5 vs 2.6 ± 0.5 L min-1 ) without influencing ventilation (86 ± 9 vs 82 ± 10 L min-1 ; P > 0.05), for PAV and post-PAV respectively. During 80% peak work (n = 8), the ventilator significantly (P V ˙ O 2 (2.9 ± 0.6 vs 3.2 ± 0.7 L min-1 ) but not ventilation (121 ± 20 vs 123 ± 20 L min-1 ; P > 0.05), for PAV and post-PAV respectively. There was a significant relationship between MSNA and V ˙ O 2 (P

Industrial sites present a challenge to the hydrogeological delineation of pollution sources and their impacts. When large-scale geologic structures such as grabens exist on such sites, these can have a significant impact on the hydrology and water quality distribution. At the site investigated, geophysical techniques, standard hydrogeological approaches and hydrochemical characterisation (with methods such as depth-profiling and isotopes) were used to determine the impact of a graben structure and the hydrogeological properties and consequent water quality distribution. Zones of high conductivity, corresponding with available data, were identified from the geophysical investigation and subsequent pumping tests in the area. Through hydrochemical characterisation, including isotopes, it was determined that the fault zone acts as a barrier for groundwater flow and is thus the reason for the lower levels of pollutants in groundwater beyond this feature. However, the surface water flow is not restricted by these zones, and contributes significantly to the flow and salt loads at the discharge point. The study showed that graben structures are important controls on the movement of contaminants, and that the effect of such geological features on groundwater quality distribution must be investigated using multiple methodologies to construct a feasible conceptual model of the interactions.

The main challenge facing many of the coal mines in South Africa is the management of mine water following the closure of mining operations. The Sigma Colliery is situated in the Free State Province, adjacent to the town of Sasolburg and bordering the Vaal River, one of the country's largest rivers. The mining includes both opencast and underground operations; however, this paper will only discuss the main underground operations. There are several aquifer systems overlying the deeper mining, which was done by bord and pillar and high extraction mining. Detailed conceptual models of the interactions between several aquifer systems and the rebounding mine voids were constructed using mining and monitoring data. From this, numerical flow models were used to model the complex flow system where rebound of water levels is expected. The results have led to an accurate understanding of the complex flow system and the important controls on the final water levels in the area.