Jesper Mehlsen

Rigshospitalet | rigshospitalet · Section of Surgical Pathophysiology

Patients with severe traumatic brain injury (TBI) may have autonomic dysfunction, one manifestation of which is orthostatic intolerance. This potentially impairs physical rehabilitation. However, the exact mechanisms remain elusive. In 30 patients participating in a trial of early tilt training versus standard care and 15 healthy volunteers, 5-min...

Aims: The autonomic nervous system includes parasympathetic and sympathetic components that monitor and regulate most of the bodily functions and play a central role in the physiology and homeostasis of the human body. Heart rate variability is a non-invasive tool for quantification of rhythmic fluctuations in heart rate that reflects the function...

Patients with postural orthostatic tachycardia syndrome (POTS) experience an excessive increase in heart rate (HR) and low-frequency (∼0.1 Hz) blood pressure (BP) and HR oscillations upon head-up tilt (HUT). These responses are attributed to increased baroreflex (BR) responses modulating sympathetic and parasympathetic signalling. This study uses a...

Background Early mobilization on a tilt table with stepping versus standard care may be beneficial for patients with severe brain injury, but data from randomized clinical trials are lacking. This detailed statistical analysis plan describes the analyses of data collected in a randomized clinical feasibility trial for early mobilization by head-up...

Cerebral autoregulation is a complex mechanism that serves to keep cerebral blood flow relatively constant within a wide range of cerebral perfusion pressures. The mean flow index (Mx) is one of several methods to assess dynamic cerebral autoregulation, but its reliability and validity have never been assessed systematically. The purpose of the pre...

In patients with severe traumatic brain injury, there is limited evidence of the clinical effect of early orthostatic exercise, although such exercise may strengthen systemic or cerebral hemodynamic responses to head-up tilt, thereby minimizing orthostatic intolerance. We measured dynamic cerebral autoregulation (dCA) and the occurrence of orthosta...

Recent studies have shown that Postural Orthostatic Tachycardia Syndrome (POTS) patients have abnormal low frequency $\approx 0.1$ Hz blood pressure and heart rate dynamics. These dynamics are attributed to the baroreflex and can give insight into the mechanistic causes which are the basis for proposed subgroups of POTS. In this study we develop a...

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous, debilitating, and complex disease. Along with disabling fatigue, ME/CFS presents an array of other core symptoms, including autonomic nervous system (ANS) dysfunction, sustained inflammation, altered energy metabolism, and mitochondrial dysfunction. Here, we evaluated p...

Background: Intensive rehabilitation of patients after severe traumatic brain injury aims to improve functional outcome. The effect of initiating rehabilitation in the early phase, in the form of head-up mobilization, is unclear. Objective: To assess whether early mobilization is feasible and safe in patients with traumatic brain injury admitted to...

Imbalance in the autonomic nervous system can lead to orthostatic intolerance manifested by dizziness, lightheadedness, and a sudden loss of consciousness (syncope); these are common conditions, but they are challenging to diagnose correctly. Uncertainties about the triggering mechanisms and the underlying pathophysiology have led to variations in...

The transcranial Doppler ultrasound-derived mean flow index (Mxa) is widely used for assessing dynamic cerebral autoregulation (dCA) in different clinical populations. This study aimed at estimating the relative and absolute reliability of Mxa in healthy participants in the supine position and during head-up tilt (HUT). Fourteen healthy participant...

Key points: Inflammation in response to bacterial endotoxin challenge impacts physiological functions including cardiovascular, thermal, and pain dynamics, but the mechanisms are poorly understood. We develop an innovative mathematical model, incorporating interaction pathways between inflammation and physiological processes observed in response t...

Background There is increasing focus on earlier rehabilitation in patients with traumatic or hypoxic brain injury or stroke. This systematic review evaluates the benefits and harms of early head-up mobilisation versus standard care in patients with severe acquired brain injury. Methods We searched Medline, CENTRAL, EMBASE, four other databases and...

Objective: Postural Orthostatic Tachycardia Syndrome (POTS) is associated with the onset of tachycardia upon postural change. The current diagnosis involves the measurement of heart rate (HR) and blood pressure (BP) during head-up tilt (HUT) or active standing test. A positive diagnosis is made if HR changes with more than 30 bpm (40 bpm in patien...

Background: Early mobilisation on a tilt table with stepping versus standard care may be beneficial for patients with severe brain injury, but data from randomised clinical trials are lacking. Methods: This detailed statistical analysis plan describes the analyses of data collected in a randomised clinical feasibility trial for early mobilisation b...

Postural Orthostatic Tachycardia Syndrome (POTS) is associated with the onset of tachycardia upon postural change. The current diagnosis involves the measurement of heart rate (HR) and blood pressure (BP) during head-up tilt (HUT) or sit-to-stand test. A positive diagnosis is made if HR changes more than 40 bpm (30 bpm in children younger than 20),...

Uncontrolled, excessive production of pro-inflammatory mediators from immune cells and traumatized tissues can cause systemic inflammatory issues like sepsis, one of the ten leading causes of death in the United States and one of the three leading causes of death in the intensive care unit. Understanding the effects of inflammation on the autonomic...

This study develops non-pulsatile and pulsatile models for the prediction of blood flow and pressure during head-up tilt. This test is used to diagnose potential pathologies within the autonomic control system, which acts to keep the cardiovascular system at homeostasis. We show that mathematical modeling can be used to predict changes in cardiac c...

The Valsalva maneuver (VM) is a diagnostic protocol examining sympathetic and parasympathetic activity in patients with autonomic dysfunction (AD) impacting cardiovascular control. Since direct measurement of these signals is costly and invasive, AD is typically assessed indirectly by analyzing heart rate and blood pressure response patterns. This...

Background: Early mobilisation on a tilt table with stepping versus standard care may be beneficial for patients with severe brain injury, but data from randomised clinical trials are lacking. Methods: This statistical analysis plan describes the analyses of data collected in a randomised clinical feasibility trial for early mobilisation by head-up...

In this review, we discuss the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is characterised by extreme mental and physical fatigue with associated symptoms of pain, disturbed sleep, cognitive and autonomic dysfunction, as well as post-exertional malaise. This con-dition is often preceded by an infection, severe physiological...

This paper presents an optimal control approach to modeling effects of cardiovascular regulation during head-up tilt (HUT). Many patients who suffer from dizziness or light-headedness are administered a head-up tilt test to explore potential deficits within the autonomic control system, which maintains the cardiovascular system at homeostasis. This...

Background: Early mobilisation on a tilt table with stepping versus standard care may be beneficial for patients with severe brain injury, but data from randomised clinical trials are lacking. Methods: This statistical analysis plan describes the analyses of the data collected in the randomised clinical feasibility trial for early mobilisation by h...

In contrast to the insidious and poorly immunogenic human papillomavirus (HPV) infections, vaccination with the HPV virus-like particles (vlps) is non-infectious and stimulates a strong neutralizing-antibody response that protects HPV-naïve vaccinees from viral infection and associated cancers. However, controversy about alleged adverse events foll...

Background: Intensive rehabilitation of patients with severe traumatic brain injury is generally applied in the subacute stages of the hospital stay. Few studies have assessed the association between early and intensive physical rehabilitation and functional outcomes. The aim of this trial is to assess the feasibility of an intensive physical rehab...

Introduction: Human papilloma virus (HPV) vaccine uptake in girls and women is dropping markedly in some countries. Concern about the presumed side effects is the commonest reason why. Reports about side effects include specific sleep complaints such as excessive daytime sleepiness, altered dream activity and periods of muscle weakness. These symp...

Postural orthostatic tachycardia syndrome is a hetero-geneous condition of dysautonomia and suspected autoimmunity characterised by abnormal increments in heart rate upon assumption of the upright posture accompanied by symptoms of cerebral hypoperfusion and sympathoexcitation. An increase in heart rate equal to or greater than 30 bpm or to levels...

Aims: The incidence of Postural Orthostatic Tachycardia Syndrome (POTS) has grown in recent years. Whether this is an emerging epidemic or increasing recognition is unclear. Methods: We retrospectively examined 8790 tilt-table tests (HUT) performed between 1997 and 2014 in patients with orthostatic intolerance and/or suspected syncope. Tests wer...

Semen quality is suggested to be a universal biomarker for future health. Previous studies have mostly been registry based excluding the possibility to address the importance of lifestyle, fertility status, health and socio-economic status. We aimed to investigate whether the association between semen quality and subsequent risk of hospitalization...

The objective of this study was to develop a personalized inflammatory model and estimate subject-specific parameters that could be related to changes in heart rate variability (HRV), a measure that can be obtained non-invasively in real time. An inflammatory model was developed and calibrated to measurements of interleukin-6 (IL-6), tumor necrosis...

Primary objective: This study aimed to investigate the effect of intravenous saline administration on orthostatic hypotension (OH) during head up tilt (HUT) and the change in the renin-angiotensin-aldosterone system before and after HUT in patients with severe acquired brain injury (ABI). Research design: The study is designed as an observationa...

Objectives: We describe the final 10-year data for the long-term follow-up study of the 4-valent human papillomavirus (4vHPV) vaccine in preadolescents and adolescents. Methods: In the base study (V501-018), 1661 sexually inactive boys and girls received the 4vHPV vaccine (early vaccination group [EVG], managed for 9.9 years) or a placebo at day...

Introduction: Cluster headache is characterized by attacks of severe unilateral pain accompanied by cranial and systemic autonomic changes. Our knowledge of the latter is imperfect. This study aimed to investigate the effect of low-frequency sphenopalatine ganglion stimulation on cardiac autonomic regulation. Materials and methods: In a double-b...

Aim No association between human papilloma virus (HPV) vaccination and numerous diseases has been found. Still, a large number of Danish women are reporting suspected adverse events. Other factors may play a role, and the aim of this study is to examine the association between psychiatric conditions, general practitioner (GP) attendance and indicat...

T-wave amplitude (TWA) has been proposed as a marker of the innervation of the myocardium. Until now, TWA has been calculated manually or with poor algorithms, thus making its use not efficient in a clinical environment. We introduce a new wavelet-based algorithm for the delineation QRS complexes and T-waves, and the automatic calculation of TWA. W...

During the last decade, there has been an increasing interest in the coupling between the acute inflammatory response and the Hypothalamic-Pituitary-Adrenal (HPA) axis. The inflammatory response is activated acutely by pathogen- or damage-related molecular patterns, whereas the HPA axis maintains a long-term level of the stress hormone cortisol whi...

Semen quality is suggested to be a biological marker of long-term morbidity and mortality; however, few studies have been conducted on this subject. We identified 5,785 men seen for infertility in Frederiksberg Hospital, Denmark from 1977-2010, and 4,712 men were followed in the Danish National Patient Registry until first hospitalization, death or...

Thomas Meinertz Dantoft,1 Jeanette Frost Ebstrup,1 Allan Linneberg,1–3 Sine Skovbjerg,1 Anja Lykke Madsen,1 Jesper Mehlsen,4 Louise Brinth,4 Lene Falgaard Eplov,5 Tina Wisbech Carstensen,6,7 Andreas Schroder,6,7 Per Klausen Fink,6,7 Erik Lykke Mortensen,8 Torben Hansen,9 Oluf Pedersen,9 Torben Jørgensen1,10,11 1Research Centre for Prevention and He...

Cannabis use has been found to stimulate appetite and potentially promote weight gain via activation of the endocannabinoid system. Despite the fact that the onset of cannabis use is typically during adolescence, the association between adolescence cannabis use and long-term change in body weight is generally unknown. This study aims to examine the...

Frequency of baseline cannabis use—supplementary test. (DOCX)

Mean changes in BMI (95%CI) according to baseline cannabis use—the supplementary test. (DOCX)

The initial reaction of the body to pathogenic microbial infection or severe tissue trauma is an acute inflammatory response. The magnitude of such a response is of critical importance, since an uncontrolled response can cause further tissue damage, sepsis, and ultimately death, while an insufficient response can result in inadequate clearance of p...

Objective: Syncope is a sudden loss of consciousness with loss of postural tone and spontaneous recovery; it is a common condition, albeit one that is challenging to accurately diagnose. Uncertainties about the triggering mechanisms and their underlying pathophysiology have led to various classifications of patients exhibiting this symptom. This st...

We aimed to study the relationship between pain perception and cytokine release during systemic inflammation. We present a randomized crossover trial in healthy volunteers (n = 17) in 37 individual trials. Systemic inflammation was induced by an i.v. bolus of Escherichia coli LPS (2 ng/kg) on two separate trial days, with or without a nicotine patc...

T-wave amplitude (TWA) is a well know index of the autonomic innervation of the myocardium. However, until now it has been evaluated only manually or with simple and inefficient algorithms. In this paper, we developed a new robust single-lead electrocardiogram (ECG) T-wave delineation algorithm that is able to detect the T-wave with a wavelet based...

Early mobilization is of importance for improving long-term outcome for patients after severe acquired brain injury. A limiting factor for early mobilization by head-up tilt is orthostatic intolerance. The purpose of the present study was to examine cerebral autoregulation in patients with severe acquired brain injury and a low level of consciousne...

Change from baseline. Change in MAP, HR, CPP, MCA Vmean and rScO2 for patients and healthy controls. * denotes between group difference in change from baselines (P < 0.05). (TIF)

Subject characteristics. Excel file containing data from Table 1 and in text data. (XLSX)

Power spectral analysis. Pooled power spectral analysis of the RR intervals at baseline (A&D) and head-up tilt (HUT) (B&E) for patients (PT) and healthy controls (HC), respectively. Log10 ratio of pooled power spectra between baseline and HUT for the healthy controls (C) and the patients (F) and between healthy controls and patients at baseline (G)...

Central and cerebral hemodynamics. Excel file containing data from Table 2 and in text data. (XLSX)

Flow index (Mx). Excel file containing data from Table 3 and in text data. (XLSX)

Objectives: Upright tilt is an important tool for early mobilization of patients after severe acquired brain injury (ABI). Early mobilization is considered to be of importance for increasing awareness, in the prevention of contractures and pulmonary infections and to improve long-term outcome. A challenge for early mobilization is orthostatic insta...

Background: Early postoperative mobilization is essential for rapid recovery but may be impaired by orthostatic intolerance (OI) and orthostatic hypotension (OH), which are highly prevalent after major surgery. Pathogenic mechanisms include an insufficient postoperative vasopressor response. The oral α-1 agonist midodrine hydrochloride increases v...

The diagnosis of recurrent syncope in patients with pacemakers (PM) is quite challenging and the etiology of syncope is often multifactorial. To portray the mechanism of syncope in PM patients, we report the results of head-up tilt table testing (HUT) in a series of patients with PM, originally implanted for reasons other than neurally mediated syn...

BACKGROUND: Intact orthostatic blood pressure regulation is essential for early mobilization after surgery. However, postoperative orthostatic hypotension and intolerance (OI) may delay early ambulation. The mechanisms of postoperative OI include impaired vasopressor responses relating to postoperative autonomic dysfunction. Thus, based on a previo...

The quad rivalent human papilloma virus vaccine (Q-HPV-vaccine) was included into the Danish childhood vaccination program in 2009. During the past years possible side effects have been described in several countries encompassing a collection of symptoms consistent with pronounced autonomic dysfunction coupled with severe non-migraine-like headache...

Important elements of cluster headache (CH) pathophysiology may be seated in the posterior hypothalamus. Cranial autonomic features are inherent, but involvement of systemic autonomic control is still debated. We aimed to characterize autonomic function as investigated by baroreflex sensitivity (BRS) in CH patients. Twenty-six active CH patients an...

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous condition of dysautonomia and suspected autoimmunity characterized by abnormal increments in heart rate upon assumption of the upright posture accompanied by symptoms of cerebral hypoperfusion and sympathoexcitation. An increase in heart rate equal to or greater than 30 bpm or to l...

The quadrivalent vaccine that protects against human papilloma virus types 6, 11, 16 and 18 (Q-HPV vaccine, Gardasil) was included into the Danish childhood vaccination programme in 2009. During the past years, a collection of symptoms primarily consistent with sympathetic nervous system dysfunction have been described as suspected side effects to...

A nine-valent human papillomavirus (9vHPV) vaccine has recently been reported to be safe and highly efficacious against infection and disease related to HPV6/11/16/18/31/33/45/52/58. We evaluated the immunogenicity and safety of the 9vHPV vaccine administered concomitantly with REPEVAX (diphtheria, tetanus, acellular pertussis, and inactivated poli...

Cluster headache (CH) is a disabling headache disorder with chronobiological features. The posterior hypothalamus is involved in CH pathophysiology and is a hub for autonomic control. We studied autonomic response to the head-up tilt table test (HUT) including heart rate variability (HRV) in CH patients and compared results to healthy controls. Twe...

The cardiovascular control system is continuously engaged to maintain homeostasis, but it is known to fail in a large cohort of patients suffering from orthostatic intolerance. Numerous clinical studies have been put forward to understand how the system fails, yet non-invasive clinical data are sparse, typical studies only include measurements of h...

BACKGROUND: The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women...

Background: Falls and syncope in the elderly may be caused by hypersensitivity in the high-pressure baroreflex control-carotid sinus syndrome (CSS). The pathophysiological process causing CSS remains poorly understood.

The rationale for the ASCOT study was to answer the issue of whether a newer combination of antihypertensive agents, a dihydropyridine calcium channel blocker (CCB) and an angiotensin converting enzyme (ACE) inhibitor, would produce greater benefits in terms of reducing coronary heart disease (CHD) events than the standard betablocker/ diuretic com...

Background: We present a long-term safety, immunogenicity, and effectiveness study of a quadrivalent human papillomavirus (HPV4) vaccine. Methods: Sexually naive boys and girls aged 9 to 15 years (N = 1781) were assigned (2:1) to receive HPV4 vaccine or saline placebo at day 1 and months 2 and 6. At month 30, the placebo group (n = 482) received...

This study investigates ECG features, focusing on T-wave amplitude, from a wearable ECG device as a potential method for fitness monitoring in exercise rehabilitation. An automatic T-peak detection algorithm is presented that uses local baseline detection to overcome baseline drift without the need for preprocessing, and offers adequate performance...

We consider the inverse and patient specific problem of short term (seconds to minutes) heart rate regulation specified by a system of nonlinear ODEs and corresponding data. We show how a recent method termed the structural correlation method (SCM) can be used for model reduction and for obtaining a set of practically identifiable parameters. The s...

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous condition of dysautonomia and suspected autoimmunity characterized by abnormal increments in heart rate upon assumption of the upright posture accompanied by symptoms of cerebral hypoperfusion and sympathoexcitation. An increase in heart rate equal to or greater than 30 bpm or to l...