Automatic adjustment of pressure support by a computer-driven knowledge-based system during noninvasive ventilation: a feasibility study

Objective

To evaluate the feasibility of using a knowledge-based system designed to automatically titrate pressure support (PS) to maintain the patient in a “respiratory comfort zone” during noninvasive ventilation (NIV) in patients with acute respiratory failure.

Design and setting

Prospective crossover interventional study in an intensive care unit of a university hospital.

Patients

Twenty patients.

Interventions

After initial NIV setting and startup in conventional PS by the chest physiotherapist NIV was continued for 45?min with the automated PS activated.

Measurements and results

During automated PS minute-volume was maintained constant while respiratory rate decreased significantly from its pre-NIV value (20?±?3 vs. 25?±?3?bpm). There was a trend towards a progressive lowering of dyspnea. In hypercapnic patients PaCO₂ decreased significantly from 61?±?9 to 51?±?2?mmHg, and pH increased significantly from 7.31?±?0.05 to 7.35?±?0.03. Automated PS was well tolerated. Two system malfunctions occurred prompting physiotherapist intervention.

Conclusions

The results of this feasibility study suggest that the system can be used during NIV in patients with acute respiratory failure. Further studies should now determine whether it can improve patient-ventilator interaction and reduce caregiver workload.

     

Regional lung derecruitment after endotracheal suction during volume- or pressure-controlled ventilation: a study using electric impedance tomography

Objective

To assess lung volume and compliance changes during open- and closed-system suctioning using electric impedance tomography (EIT) during volume- or pressure-controlled ventilation.

Design and setting

Experimental study in a university research laboratory.

Subjects

Nine bronchoalveolar saline-lavaged pigs.

Interventions

Open and closed suctioning using a 14-F catheter in volume- or pressure-controlled ventilation at tidal volume 10?ml/kg, respiratory rate 20?breaths/min, and positive end-expiratory pressure 10?cmH₂O.

Measurements and results

Lung volume was monitored by EIT and a modified N₂ washout/-in technique. Airway pressure was measured via a pressure line in the endotracheal tube. In four ventral-to-dorsal regions of interest regional ventilation and compliance were calculated at baseline and 30?s and 1, 2, and 10?min after suctioning. Blood gases were followed. At disconnection functional residual capacity (FRC) decreased by 58?±?24% of baseline and by a further 22?±?10% during open suctioning. Arterial oxygen tension decreased to 59?±?14% of baseline value 1?min after open suctioning. Regional compliance deteriorated most in the dorsal parts of the lung. Restitution of lung volume and compliance was significantly slower during pressure-controlled than volume-controlled ventilation.

Conclusions

EIT can be used to monitor rapid lung volume changes. The two dorsal regions of the lavaged lungs are most affected by disconnection and suctioning with marked decreases in compliance. Volume-controlled ventilation can be used to rapidly restitute lung aeration and oxygenation after lung collapse induced by open suctioning.

     

Prone equals prone? Impact of positioning techniques on respiratory function in anesthetized and paralyzed healthy children

Objectives

Although the prone position is effectively used to improve oxygenation, its impact on functional residual capacity is controversial. Different techniques of body positioning might be an important confounding factor. The aim of this study was to determine the impact of two different prone positioning techniques on functional residual capacity and ventilation distribution in anesthetized, preschool-aged children.

Design

Functional residual capacity and lung clearance index, a measure of ventilation homogeneity, were calculated using a sulfur-hexafluoride multibreath washout technique. After intubation, measurements were taken in the supine position and, in random order, in the flat prone position and the augmented prone position (gel pads supporting the pelvis and the upper thorax).

Setting

Pediatric anesthesia unit of university hospital.

Patients and participants

Thirty preschool children without cardiopulmonary disease undergoing elective surgery.

Measurements and results

Mean (range) age was 48.5 (24–80) months, weight 17.2 (10.5–26.9)?kg, functional residual capacity (mean ±?SD) 22.9?±?6.2?ml.kg ^?1 in the supine position and 23.3?±?5.6?ml.kg ^?1 in the flat prone position, while lung clearance indices were 8.1?±?2.3 vs. 7.9?±?2.3, respectively. In contrast, functional residual capacity increased to 27.6 ± 6.5 ml.kg ^?1 (pp

Conclusions

Functional residual capacity and ventilation distribution were similar in the supine and flat prone positions, while these parameters improved significantly in the augmented prone position, suggesting that the technique of prone positioning has major implications for pulmonary function.

     

Lack of agreement between thermodilution and electrical velocimetry cardiac output measurements

Objective

The modified algorithm for the non-invasive determination of cardiac output (CO) by electrical bioimpedance—electrical velocimetry (EV^®)—has been reported to give reliable results in comparison with echocardiography and pulmonary arterial thermodilution (PA-TD) in patients either before or after cardiac surgery. The present study was designed to determine whether EV^®-CO measurements reflect intraindividual changes in CO during cardiac surgery.

Design

Prospective, observational study.

Setting

Operating room (OR) and intensive care unit (ICU) of a university hospital.

Patients

Twenty-nine patients undergoing elective cardiac surgery.

Interventions

None.

Measurements

CO was determined simultaneously by PA-TD and EV^® after induction of anesthesia (t1) and 4.9?±?3.5?h after ICU admission (t2).

Results

TD-CO was 3.9?±?1.4 and 5.4?±?1.1 l/min at t1 and t2 (?p?®-CO was 4.3?±?1.1 and 4.9?±?1.5 l/min at t1 and t2 (?p?=?0.013). Bland–Altman analysis showed a bias of ?0.4 l/min and 0.4 l/min and a precision of 3.2 and 3.6 l/min (34.3% and 67.4%) at t1 and t2, respectively. Analysis of the individual pre- to postoperative changes in CO with both methods revealed bidirectional changes in n?=?12 patients and unidirectional changes with a difference greater than 50% and less than 50% in n?=?9 and n?=?8 patients, respectively.

Conclusions

The disagreement between PA-TD and EV^®-CO measurements after anesthesia induction and after ICU admission, as well as the fact that thoracic bioimpedance did not adequately reflect pre- to postoperative changes in CO, questions the reliability of EV^®-CO measurements in cardiac surgery patients and contrasts sharply with previous studies.

     

„Foam rolling“ und Wirbelsäulenbeweglichkeit – eine randomisierte kontrollierte Pilotstudie

Background

Despite limited evidence and little knowledge about underlying mechanisms or even potential risks, foam rolling (FR) has become a widely used tool for fitness and health purposes. Improvements in lower limb flexibility have been described, but there is a paucity of information for the spine.

Purpose

This pilot study aimed to investigate the effects of FR on trunk and spinal flexion and axial rotation in healthy subjects.

Methods

Spinal flexibility at maximal trunk flexion (sit and reach test) and maximal vertebral axial rotation (segments L1 and T4, dynamic video rasterstereography) was assessed in a randomized controlled repeated measures design (experimental and waiting control conditions separated by 1 week) before and after FR or a respective waiting time (control) in a sample of 19 active healthy females (age 26.1?±?3.6 years, body mass index 22.3?±?2.6?kg/m²). FR consisted of 2 repetitions (each 3?min with 60?s rest) for the paraspinal and lateral back muscles (10 roll cyles/min, average pressure approximately two thirds of body weight).

Results

We found a significant 2?cm increase in the sit and reach test results (p?<?0.001), which was, however, independent of the FR treatment (p?=?0.910). Vertebral rotation (L1, T4) did not change significantly (p?=?0.290–0.941). Although we observed 2?degree increases on average for the FR condition only, the time?×?treatment interactions did not indicate an FR effect (p?=?0.261–0.368).

Conclusion

Commonly accepted evidence for increases in lower limb flexibility after FR cannot be confirmed for spinal mobility after a single treatment in healthy active young women. The technical approach using dynamic rasterstereography to quantify axial spinal rotation appears to be promising for future FR investigations targeting patients with back complaints, provided methodical adaptations are taken into account.

     

Pooled Aquablation Results for American Men with Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia in Large Prostates (60–150 cc)

Introduction

To present short-term safety and efficacy data of men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) treated with Aquablation.

Methods

Men with LUTs secondary to BPH (60–150 cc) underwent Aquablation treatment from February 2016 to December 2017 across 17 investigational sites in the USA from two contemporary investigational device exemption (IDE) studies called WATER (NCT02505919) and WATER II (NCT03123250).

Results

One hundred seven males with mean age of 67.3?±?6.5 years were treated with Aquablation; mean prostate volume was 99.4?±?24.1 cc. The pooled results show that large prostates have an average procedure time of less than 36 min and discharge on average 1.6?±?1 days. The IPSS decreased by 16.7?±?8.1 points at 3 months and Q_max increased by 11.2?±?12.4 ml/s. The Clavien-Dindo (CD) grade 2 or higher event rate at 3 months was 29%. A non-hierarchical breakdown for CD events yielded 18% grade 2 and 19% grade 3 or higher.

Conclusion

Men with LUTS secondary to BPH (60–150 cc) in a pooled analysis were treated safely and effectively with Aquablation up to 3 months postoperatively.

Trial Registration

ClinicalTrials.gov identifiers, NCT02505919 and NCT03123250.

Funding

PROCEPT BioRobotics.

     

Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

Purpose

The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer.

Procedures

CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated in a xenograft breast cancer mouse model using ductal carcinoma in situ cells (DCIS).

Results

Specific anti-CAIX nanobodies were obtained. Administration of a CAIX-specific nanobody into mice with DCIS xenografts overexpressing CAIX showed after 2 h a mean tumor-to-normal tissue ratio (TNR) of 4.3?±?0.6, compared to a TNR of 1.4?±?0.2 in mice injected with the negative control nanobody R2-IR. In DCIS mice, a TNR of 1.8?±?0.1 was obtained. Biodistribution studies demonstrated an uptake of 14.0?±?1.1 %I.D./g in DCIS?+?CAIX tumors, 4.6?±?0.8 %I.D./g in DCIS tumors, while 2.0?±?0.2 %I.D./g was obtained with R2-IR.

Conclusions

These results demonstrate the successful generation of a CAIX-specific nanobody-IRDye800CW conjugate that can be used for rapid imaging of (pre-)invasive breast cancer.

     

Phase 1 Evaluation of [<Superscript>64</Superscript>Cu]DOTA-Patritumab to Assess Dosimetry,Apparent Receptor Occupancy,and Safety in Subjects with Advanced Solid Tumors

Purpose

The purpose of this study was to evaluate the safety, dosimetry, and apparent receptor occupancy (RO) of [⁶⁴Cu]DOTA-patritumab, a radiolabeled monoclonal antibody directed against HER3/ERBB3 in subjects with advanced solid tumors.

Procedures

Dosimetry subjects (n?=?5) received [⁶⁴Cu]DOTA-patritumab and underwent positron emission tomography (PET)/X-ray computed tomography (CT) at 3, 24, and 48 h. Evaluable RO subjects (n?=?3 out of 6) received [⁶⁴Cu]DOTA-patritumab at day 1 and day 8 (after 9.0 mg/kg patritumab) followed by PET/CT at 24 h post-injection. Endpoints included safety, tumor uptake, and efficacy.

Results

The tumor SUV_max (±?SD) was 5.6?±?4.5, 3.3?±?1.7, and 3.0?±?1.1 at 3, 24, and 48 h in dosimetry subjects. The effective dose and critical organ dose (liver) averaged 0.044?±?0.008 mSv/MBq and 0.46?±?0.086 mGy/MBq, respectively. In RO subjects, tumor-to-blood ratio decreased from 1.00?±?0.32 at baseline to 0.57?±?0.17 after stable patritumab, corresponding to a RO of 42.1?±?3.

Conclusions

[⁶⁴Cu]DOTA-patritumab was safe. These limited results suggest that this PET-based method can be used to determine tumor-apparent RO.

     

Impact of Insulin Degludec in Hospitalized Patients With and Without Type 2 Diabetes Requiring Parenteral/Enteral Nutrition: An Observational Study

Introduction

Hyperglycemia in inpatients is a major problem, especially when nutritional support is required. This study aims to assess the impact of treatment with insulin degludec (IDeg) on mean blood glucose (BG) and glycemic variability in noncritical hospitalized patients with and without type 2 diabetes (T2DM) receiving enteral and/or parenteral nutrition (EN, PN).

Methods

Mean BG and glycemic variability from admission up to 7 days of hospitalization were evaluated in consecutive cases with and without T2DM. Percentage of coefficient of variation (CV) for glucose was used to express glycemic variability.

Results

Overall, 26 patients (13 with and 13 without T2DM) were admitted to the hospital for any cause. Subjects were 65.4% men and they were mainly elderly (mean age 66.3?±?13.4 years). PN was administered in 88.5% of patients and EN in 19.2%. At admission, mean HbA1c level was 5.9?±?0.7% in patients without diabetes and 9.1?±?2.5% in patients with T2DM. During hospitalization, mean daily BG levels changed from 151?±?47.3 mg/dl (day 1) to 157?±?66.7 mg/dl (day 7) in patients without diabetes and from 210?±?66.5 mg/dl to 192?±?48.6 mg/dl in patients with T2DM. CV decreased from 14% (day 1) to 11% (day 7) in patients without diabetes and from 20% (day 1) to 9% (day 7) in patients with T2DM. No symptomatic or severe hypoglycemia occurred.

Conclusions

Despite the small sample size and the lack of control group, this study represents the first proof-of-concept that IDeg in hospitalized patients with or without T2DM who require nutritional support has the potential to maintain stable levels of BG and reduce glycemic variability.

Funding

Novo Nordisk S.p.A. grant.

     

Efficacy and Tolerability of Fixed-Dose Combination Perindopril/Indapamide in Hypertensive Patients with a History of Stroke or Transient Ischemic Attack: PICASSO Trial

Introduction

In everyday medical practice, physicians often need to manage patients whose blood pressure is not well controlled. Those with a history of cerebrovascular disease are a high-risk group in need of rapid blood pressure control.

Methods

The PICASSO study was a real-life, observational trial involving 9257 inadequately treated hypertensive patients who were switched from previous therapy to the fixed-dose combination of perindopril 10 mg/indapamide 2.5 mg (PI) for 3 months. A subanalysis of data of 1117 hypertensive patients who met the clinical criteria of previous stroke or transient ischemic attack was performed. Twenty-four hour ambulatory blood pressure measurements (ABPMs) were also done in a small group of patients (n:38).

Results

At baseline, mean systolic/diastolic blood pressure (SBP/DBP) was 161.5?±?15.2/93.1?±?9.9 mmHg. After 1 month with the fixed dose of PI, average office SBP/DBP decreased to 140.0?±?11.9/83.5?±?7.7 mmHg. After 3 months, SBP/DBP had dropped to 132.9?±?9.8/80.0?±?6.2 mmHg, by 28.6?±?15.5/13.1?±?10.0 mmHg (p?<?0.001). Blood pressure control rate (<?140/90 mmHg) was 67.3% after 3 months. When data were stratified by baseline blood pressure, decreases in SBP/DBP were statistically significant in patients with all grades (1–3) of hypertension. In patients previously treated with an angiotensin-converting enzyme inhibitor?±?hydrochlorothiazide (n?=?677), blood pressure decreased by 29.8?±?15.5/13.3?±?10.2 mmHg (p?<?0.001). Decreases in 24-h ABPM values were also significant (n?=?38). Treatment was well tolerated; only a few adverse events were recorded.

Conclusion

This study suggests that fixed combination perindopril 10 mg/indapamide 2.5 mg is an effective and well-tolerated treatment for patients with a history of stroke or transient ischemic attack.

Funding

EGIS Pharmaceuticals Plc.

     

Administration of Micronized Purified Flavonoid Fraction During Sclerotherapy of Reticular Veins and Telangiectasias: Results of the National,Multicenter, Observational Program VEIN ACT PROLONGED-C1

Introduction

Sclerotherapy is a common technique for the removal of intradermal veins. This study examined the rationale for prescribing micronized purified flavonoid fraction (MPFF) in clinical, etiological, anatomic, pathophysiologic (CEAP) class C1 patients with dilated intradermal veins scheduled for sclerotherapy.

Methods

In a national, multicenter, observational program, physicians recruited CEAP C1s patients scheduled for sclerotherapy. The decision to prescribe adjuvant MPFF (1000 mg/day for 6 weeks beginning 2 weeks before sclerotherapy) was made according to usual practice. Disease severity and treatment outcomes were assessed at baseline and 4 weeks post-sclerotherapy using a visual analog scale (VAS) as well as quality-of-life (CIVIQ-14) and patient satisfaction (Darvall) questionnaires.

Results

A total of 70 physicians recruited 1150 patients: 1071 (93%) women, 79 (7%) men. Mean age (±?SD) was 40.7?±?10.7 years (range 18–74) and mean body mass index was 23.6?±?3.3 kg/m². Reticular veins were observed in 42.1% of patients and 57.9% had telangiectasias. MPPF was prescribed to 905 patients (79%). Sclerotherapy was associated with statistically significant decreases in mean VAS scores for leg heaviness, pain, sensation of swelling, night cramps, and itching. For each symptom, MPFF-treated patients showed a more pronounced improvement than those undergoing sclerotherapy alone: mean VAS pain score with MPFF decreased from 1.90?±?2.30 to 0.30?±?0.62 versus 1.72?±?1.93 to 0.52?±?0.99 with sclerotherapy alone; mean VAS leg heaviness score with MPFF decreased from 2.80?±?2.43 to 0.47?±?1.07 versus 2.38?±?2.23 to 0.76?±?0.85 with sclerotherapy alone. Patient quality-of-life indicators improved with symptom resolution, particularly pain, and for each indicator the observed improvement was greater with MPFF. The outcomes of treatment exceeded patient expectations. Fewer patients experienced sclerotherapy-induced hyperpigmentation with adjunctive MPFF versus sclerotherapy alone (33.9% versus 41.2%, respectively, P?=?0.034). No adverse events related to MPFF were observed.

Conclusion

Resolution of venous symptoms post-sclerotherapy was greater in patients treated with MPFF compared with those undergoing sclerotherapy alone, supporting the rationale for use of MPFF in patients undergoing sclerotherapy.

Funding

Servier.

     

Cardiac work is related to creatine kinase energy supply in human heart failure: a cardiovascular magnetic resonance spectroscopy study

Background

It has been hypothesized that the supply of chemical energy may be insufficient to fuel normal mechanical pump function in heart failure (HF). The creatine kinase (CK) reaction serves as the heart’s primary energy reserve, and the supply of adenosine triphosphate (ATP flux) it provides is reduced in human HF. However, the relationship between the CK energy supply and the mechanical energy expended has never been quantified in the human heart. This study tests whether reduced CK energy supply is associated with reduced mechanical work in HF patients.

Methods

Cardiac mechanical work and CK flux in W/kg, and mechanical efficiency were measured noninvasively at rest using cardiac pressure-volume loops, magnetic resonance imaging and phosphorus spectroscopy in 14 healthy subjects and 27 patients with mild-to-moderate HF.

Results

In HF, the resting CK flux (126?±?46 vs. 179?±?50 W/kg, p?< 0.002), the average (6.8?±?3.1 vs. 10.1?±?1.5 W/kg, p ?<0.001) and the peak (32?±?14 vs. 48?±?8 W/kg, p <?0.001) cardiac mechanical work-rates, as well as the cardiac mechanical efficiency (53%?±?16 vs. 79%?±?3, p <?0.001), were all reduced by a third compared to healthy subjects. In addition, cardiac CK flux correlated with the resting peak and average mechanical power (p <?0.01), and with mechanical efficiency (p?= 0.002).

Conclusion

These first noninvasive findings showing that cardiac mechanical work and efficiency in mild-to-moderate human HF decrease proportionately with CK ATP energy supply, are consistent with the energy deprivation hypothesis of HF. CK energy supply exceeds mechanical work at rest but lies within a range that may be limiting with moderate activity, and thus presents a promising target for HF treatment.

Trial registration

ClinicalTrials.gov Identifier: NCT00181259.

     

Effects of heat stress and dehydration on cognitive function in elite female field hockey players

Background

It has previously been suggested that heat exposure and hypohydration have negative effects on cognitive performance, which may impact upon sporting performance. The aim of the present study was to examine the independent effects of heat stress and hypohydration on cognitive performance in elite female field hockey players.

Methods

Eight unacclimatised elite field hockey players (age: 22?±?3 y; height: 1.68?±?0.05 m; body mass: 63.1?±?6.0 kg) completed a cognitive test battery before and after 50 min of field hockey specific exercise on a treadmill in four experimental trials; two in hot conditions (33.3?±?0.1 °C), and two in moderate (16.0?±?3.0 °C), both with and without ad libitum water intake.

Results

On the visual search test, participants were faster overall in the heat (1941 vs. 2104 ms, p?=?0.001). Response times were quicker in the heat on the Sternberg paradigm (463 vs. 473 ms, p?=?0.024) and accuracy was improved (by 1.9%, p?=?0.004). There was no effect of hydration status on any of the markers of cognitive function.

Conclusions

Overall, the findings suggest that in elite field hockey players exposure to heat enhances response times and/or accuracy on a battery of cognitive function tests. However, hypohydration does not appear to affect cognitive performance in elite field hockey players.

     

Anti-Anginal Effectiveness and Tolerability of Trimetazidine Modified Release 80 Mg Once Daily in Stable Angina Patients in Real-World Practice

Introduction

Trimetazidine (TMZ) was shown to reduce angina symptoms and increase the exercise capacity in stable angina (SA) patients. A new formulation allowing a once-daily (od) dosage could improve patients’ satisfaction and adherence.

Methods

ODA was a 3-month, observational, multicenter, prospective Russian study in SA patients with persistent symptoms despite therapy. Angina attack frequency, short-acting nitrate (SAN) consumption, adherence to antianginal medications, and overall efficacy and tolerability of TMZ 80 mg od were assessed in a real-world setting.

Results

A total of 3066 patients were included (mean age 62.8, 48% male). After 3 months, TMZ 80 mg od treatment led to a significant (p?<?0.001) decrease in angina attack frequency (from 4.7?±?3.5 to 0.9?±?1.3/week) and SAN use (from 4.5?±?3.9 to 0.7?±?1.3/week). Overall tolerability and effectiveness were rated as “very good” by the majority of physicians. Medication adherence improved significantly, with good adherence reported by 56% of patients (vs. 24% at baseline, p?<?0.0001) and non-adherence by 3% (vs. 36% at baseline, p?<?0.0001) at month 3. Patient satisfaction with TMZ od was 9.5 [on a scale of 1 to 10 (very satisfied)]. Patients reported improved physical activity: more patients reported no limitations (15% vs. 1% at baseline p?<?0.01), slight limitation (46% vs. 5% at baseline, p?<?0.001) or moderate limitation (30% vs. 23%, p?<?0.01) and fewer patients reported substantial limitation (8% vs. 52% at baseline, p?<?0.001) or very marked reduction (1% vs. 19% at baseline, p?<?0.01) at month 3.

Conclusion

In this prospective, observational study, TMZ 80 mg od effectively reduced angina attacks and SAN consumption, improved physical activity and adherence and was well tolerated in chronic SA patients.

Trial Registration

ISRCTN registry Identifier, ISRCTN97780949.

Funding

Servier.

Plain Language Summary

Plain language summary available for this article.

     

Armut und Schmerz

Background

Poverty is an important problem in Germany. The health effects of poverty can lead to a higher risk of disease and the arising of chronic affections. On the other hand chronic illness may support the development and continuance of poverty. The context of chronic pain and poverty has not been analyzed so far.

Objectives

We investigated the correlation between chronic pain and poverty.

Materials and methods

In a prospective manner we interviewed 20 patients with pain syndromes during our consultation hour regarding their household income. Further, data from the German Federal Statistical Office were analyzed with respect to the correlation between the incidence of a chronic pain diagnosis and household income.

Results

At 1546?€, the average household income of the patients studied was below the poverty level. The analyzed data showed that women suffered from chronic pain more often than men did and also had a lower income. Another economic inequality was found between Eastern and Western Germany. There was a statistically significant correlation between income and the incidence of the diagnostic codes for chronic pain (R52.1, 2, 9) for men.

Conclusion

Our investigation showed the correlation between chronic pain and poverty. A commitment and cooperation of German medical associations and federal politics is necessary to overcome this sociopolitical issue.

     

Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques

Purpose

The use of receptor-targeted antibodies conjugated to photosensitizers is actively being explored to enhance treatment efficacy. To facilitate clinical testing, we evaluated cetuximab conjugated to IRDye700DX (IR700) in cynomolgus macaques.

Procedures

Total IR700 and intact cetuximab-IR700 were measured in 51 tissues at 2 and 14 days after intravenous injection of 40 and 80 mg/kg cetuximab-IR700, respectively, and compared with an unlabeled cetuximab-dosed control group (two each per sex per time point per group).

Results

The IR700 retrieved from all tissues at 2 and 14 days after dosing was estimated at 34.9?±?1.8 and 2.53?±?0.67 % of the total dose, respectively. The tissues with the highest levels of intact cetuximab-IR700 at 2 days after dosing were the blood, lung, and skin. Formalin-fixed paraffin-embedded tissue sections at 2 days after dosing showed the highest IR700 signals in the axillary lymph node, mammary gland, and gall bladder.

Conclusions

Both IR700 and intact cetuximab-IR700 biodistributions were consistent with known epidermal growth factor receptor (EGFR) expression, and changes between 2 and 14 days were consistent with rapid metabolism and excretion of the cetuximab-IR700.

     

Non-invasive PET Imaging of PARP1 Expression in Glioblastoma Models

Purpose

The current study presents [¹⁸F]PARPi as imaging agent for PARP1 expression.

Procedures

[¹⁸F]PARPi was generated by conjugating a 2H-phthalazin-1-one scaffold to 4-[¹⁸F]fluorobenzoic acid. Biochemical assays, optical in vivo competition, biodistribution analysis, positron emission tomography (PET)/X-ray computed tomography, and PET/magnetic resonance imaging studies were performed in subcutaneous and orthotopic mouse models of glioblastoma.

Results

[¹⁸F]PARPi shows suitable pharmacokinetic properties for brain tumor imaging (IC₅₀?=?2.8?±?1.1 nM; logP_CHI?=?2.15?±?0.41; plasma-free fraction?=?63.9?±?12.6 %) and accumulates selectively in orthotopic brain tumor tissue. Tracer accumulation in subcutaneous brain tumors was 1.82?±?0.21 %ID/g, whereas in healthy brain, the uptake was only 0.04?±?0.01 %ID/g.

Conclusions

[¹⁸F]PARPi is a selective PARP1 imaging agent that can be used to visualize glioblastoma in xenograft and orthotopic mouse models with high precision and good signal/noise ratios. It offers new opportunities to non-invasively image tumor growth and monitor interventions.

     

Increased nitroglycerin-mediated vasodilation in migraineurs without aura in the interictal period

Purpose

Migraine is associated with vascular disorders, but the underlying mechanism is unknown. Nitric oxide (NO) sensitivity is believed to play a major role in migraine pathophysiology. We investigated flow-mediated vasodilatation (FMD) and nitroglycerin-mediated vasodilatation (NMD) of the brachial artery by means of a key molecular mediator, NO, in patients with migraine without aura in the interictal period whether the abnormality is found.

Methods

A total of 12 patients with migraine without aura and 12 matched healthy controls were enrolled in this study. FMD and NMD were measured in all patients and controls using brachial artery ultrasonography.

Results

There was no significant difference in brachial artery diameter between migraineurs and nonmigraineurs (3.39?±?0.68 vs 3.89?±?0.67 mm, respectively; p?=?0.083). A significant difference in FMD was not found between migraineurs and nonmigraineurs (6.94?±?5.72 vs 6.08?±?2.98%, respectively; p?=?0.651). However, NMD in migraineurs was significant higher than that in nonmigraineurs (21.56?±?7.36 vs 14.23?±?7.41%, respectively; p?=?0.024).

Conclusion

We think that patients with migraine without aura in the interictal period have selective sensitivity in dilator response to nitroglycerin and may have systemic NO sensitivity.

     

Ambulante multimodale Schmerztherapie

Background

Interdisciplinary pain therapy is nowadays the state of the art for the treatment of chronic unspecific back pain. The aim of this article is to present the retrospective analysis of the data from a 1-week intensive outpatient multimodal interdisciplinary pain therapy group program for treatment of patients with chronic unspecific back pain.

Design and methods

The questionnaire-based data from patients who attended the program were evaluated before as well as 3 and 12 months after finishing the program. The patients were questioned regarding parameters, such as pain severity, quality of life, pain-related disability, depression and pain acceptance.

Results

On average a significant improvement of all parameters after 3 and 12 months could be demonstrated (excluding the domains “social” and “environment” in the context of quality of life).

Discussion

Interestingly, the results showed a significant improvement of almost all evaluated parameters even after a period of 12 months (unfortunately only data for 41 patients were available). In our opinion this improvement is due to the special constellation of the presented program, which with 1 week is relatively short but very intensive with 34?h of treatment. In addition, the program is integrated into a long-term multimodal outpatient treatment, a concept in which the multimodal treatment is individually continued after the 1?week program. On the other hand, the results especially after 12 months have to be interpreted particularly in this context.