[Consensus recommendations on regional interdisciplinary standardization of MRI diagnostics for multiple sclerosis in the metropolitan area of Essen]. / Konsensusempfehlungen zur regionalen fächerübergreifenden Standardisierung der MRT-Diagnostik bei Multipler Sklerose im Großraum Essen.

Magnetic resonance imaging (MRI) is of exceptional importance in the diagnostics and monitoring of multiple sclerosis (MS); however, a close interdisciplinary cooperation between neurologists in private practice, (neuro)radiological practices, hospitals or specialized MS centers is only rarely established. In particular, there is a lack of standardized MRI protocols for image acquisition as well as established quality parameters, which guarantee the comparability of MRI records; however, this is a fundamental prerequisite for an effective application of MRI in the treatment of MS patients, e.g., for making the diagnosis or treatment monitoring. To address these challenges a group of neurologists and (neuro)radiologists developed a consensus proposal for standardization of image acquisition, interpretation and transmission of results and for improvement in interdisciplinary cooperation. This pilot project in the metropolitan area of Essen used a modified Delphi process and was based on the most up to date scientific knowledge. The recommendation takes the medical, economic, temporal and practical aspects of MRI in MS into consideration. The model of interdisciplinary cooperation between radiologists and neurologists with the aim of a regional standardization of MRI could serve as an example for other regions of Germany in order to optimize MRI for MS.

An Initiative to Change Inpatient Practice: Leveraging the Patient Medical Home for Postdischarge Follow-Up.

BACKGROUND: The standard of care for hospital discharge planning includes arranging follow-up appointments, usually with a primary care provider. However, follow-up phone calls instead of face-to-face visits may be an appropriate alternative for some patients. This option was explored within the framework of the US Department of Veterans Affairs (VA) patient-centered medical home model of care, the Patient Aligned Care Team. METHODS: At a VA hospital, a pilot study was conducted on the use of phone calls from members of a patient's medical home as posthospital discharge follow-up rather than the traditional face-to-face provider model. Inpatient providers were educated about the phone follow-up alternative, and this option was standardized as part of discharge planning rounds. RESULTS: During Phase 1 at one clinic over three months, 17 of 118 eligible patients received phone call follow-up (14.4% of discharges) instead of traditional face-to-face follow-up. During Phase 2, data from Phase 1 were analyzed, and staff at the other eight clinic sites were trained. After the expansion of the initiative to all regional clinic sites in Phase 3, 76 of 447 eligible discharges (17.0%) were scheduled for phone follow-up. As a balancing metric, there were no significant differences in rates of 30-day emergency department (ED) utilization (11.9% and 5.9%, (p = 0.47)) or nonelective rehospitalization (16.8% and 17.6%, (p = 0.93)) between these groups during Phase 1. CONCLUSION: This initiative changed provider practices to use phone call follow-up for select patients instead of face-to-face provider visits after hospital discharge, without significantly increasing rates of 30-day ED utilization or rehospitalization.

Hepatic arterial infusion chemotherapy for extensive liver metastases of breast cancer: efficacy, safety and prognostic parameters.

PURPOSE: Hepatic arterial infusion chemotherapy (HAIC) is an option for patients with liver-predominant metastatic breast cancer (LMBC), when no further systemic treatment is available. But systematic reports are limited. Here we conducted a retrospective analysis of LMBC patients treated at an expert center. METHODS: Individual patient data were retrieved from the clinical data base of the West German Cancer Center. Primary endpoints included hepatic response (RECIST), progression-free survival (PFS), overall survival (OS), and toxicity. A score based on LDH, AST, ALT and bilirubine was developed to estimate the hepatic metastasis load. RESULTS: Data from 70 consecutive patients were included. All patients were heavily pretreated (median 7 treatment lines for LMBC). HAIC protocols included mitomycin/5-FU (70%), mitomycin (14.3%), melphalan (12.9%) and 5-FU (7.1%), with selection based on patient characteristics. Partial hepatic remission was obtained as best response in 14 patients (20.0%), stable disease in 27 patients (38.6%), and progressive disease in 29 patients (41.4%). Median PFS and OS from initiation of HAIC were 2 (range 0-10) and 7 months (range 1-37). Mainly hepatic and hematopoietic HAIC-related toxicities were observed; there was no treatment-related death. The hepatic metastasis score effectively separated two prognostic groups: Patients with a score <3 had significantly superior PFS (15 vs 7 weeks, p = 0.017) and OS (12 vs 5 months, p = 0.002). CONCLUSION: HAIC offers a safe and effective salvage treatment strategy in heavily pretreated patients with LMBC and no further treatment options. The hepatic metastasis score may help to identify patients with sustained clinical benefit.

Commercial surrogacy: how provisions of monetary remuneration and powers of international law can prevent exploitation of gestational surrogates.

Increasing globalisation and advances in artificial reproductive techniques have opened up a whole new range of possibilities for infertile couples across the globe. Inter-country gestational surrogacy with monetary remuneration is one of the products of medical tourism meeting in vitro fertilisation embryo transfer. Filled with potential, it has also been a hot topic of discussion in legal and bioethics spheres. Fears of exploitation and breach of autonomy have sprung from the current situation, where there is no international regulation of surrogacy agreements--only a web of conflicting national laws that generates loopholes and removes safeguards for both the surrogate and commissioning couple. This article argues the need for evidence-based international laws and regulations as the only way to resolve both the ethical and legal issues around commercial surrogacy. In addition, a Hague Convention on inter-country surrogacy agreements is proposed to resolve the muddled state of affairs and enable commercial surrogacy to demonstrate its full potential.

Multisensing emissive pyrimidine.

Fluorescent nucleoside analogs, commonly used to explore nucleic acid dynamics, recognition and damage, frequently respond to a single environmental parameter. Herein we address the development of chromophores that can simultaneously probe more than one environmental factor while having each associated with a unique spectroscopic signature. We demonstrate that an isomorphic emissive pyridine-modified 2-deoxy-uridine 1, containing multiple sensory elements, responds to changes in acidity, viscosity, and polarity. Protonation of the pyridine moiety (pK(a) 4.4) leads to enhanced emission (λ(em) =388 nm) and red-shifted absorption spectra (λ(abs) =319 nm), suggesting the formation of an intramolecular hydrogen bond with the neighboring pyrimidine carbonyl. This "locked" conformation can also be mimicked by increasing solvent viscosity, resulting in a stark enhancement of emission quantum yield. Finally, increasing solvent polarity substantially impacts the chromophore's Stokes shift [from 5.8×10(3) cm(-1) at E(T) (30)=36.4 kcal mol(-1) to 9.3 ×10(3) cm(-1) at E(T) (30)=63.1 kcal mol(-1)]. The opposite effect is seen for the impact of solvent polarity of the protonated form. The characteristic photophysical signature induced by each parameter facilitates the exploration of these environmental factors both individually and simultaneously.

A randomised controlled trial on the efficacy and side-effect profile (nausea/vomiting/sedation) of morphine-6-glucuronide versus morphine for post-operative pain relief after major abdominal surgery.

Morphine is the first choice of treatment of severe post-operative pain, despite the occurrence of often discomforting (post-operative nausea or vomiting (PONV)) and sometimes dangerous (sedation, respiratory depression) side effects. Literature data indicate that morphine's active metabolite, morphine-6-glucuronide (M6G), is a powerful analgesic with a possibly more favourable side-effect profile. In this multi-centre randomised controlled clinical trial patients undergoing major abdominal surgery were randomised to M6G or morphine treatment. Treatment started 30-60 min prior to the end of surgery and was continued postoperatively, after patients were titrated to comfort, via patient-controlled analgesia (PCA) for 24-48 h. Pain intensity, nausea, vomiting and sedation scores were collected at regular intervals. In the study 268 patients were randomised to M6G and 249 to morphine. Withdrawal due to insufficient pain relief occurred predominantly just after surgery and was higher in the M6G group (16.8%) than in the morphine group (8.8%), suggesting a slower onset of analgesia for M6G compared to morphine. Subjects who continued on PCA remained equi-analgesic throughout the study. During the first 24h, nausea levels showed a 27% difference in favour of M6G which narrowly failed to reach statistical significance (P=0.052). Sub-analysis showed a significant reduction in nausea levels in females on M6G (30% difference, P=0.034). In all patients, similar reductions of 30-35% were observed in anti-emetic use, vomiting, PONV (a combined measure of nausea and vomiting) in favour of M6G, persisting for the first 24h postoperatively. Reductions in sedation were observed in the first 4h post-operative period for M6G patients.

Dose escalating safety study of CNS 5161 HCl, a new neuronal glutamate receptor antagonist (NMDA) for the treatment of neuropathic pain.

AIMS: The purpose of the current study was to establish the safety and maximal tolerated dose of CNS 5161 HCl. METHODS: Forty patients with chronic neuropathic pain (23 male, 17 female) were treated with escalating dosages of CNS 5161. All adverse events to study drug, blood pressure, heart rate, ECG, drug level and clinical laboratory values were monitored. Actual pain was measured on a 100-mm visual analogue scale (VAS) and ordinal verbal pain scores. RESULTS: The most commonly occurring nervous system disorder was headache, which was found more often during placebo than during CNS 5161 HCl treatment. Visual disturbances were experienced by 16.7% of patients receiving 250 microg and by 33.3% receiving 500 microg CNS 5161 HCl, but not during placebo treatment. An increase in blood pressure was observed in 8.3% of patients receiving 250 microg and in 50% of patients receiving 500 microg CNS 5161 HCl, compared with 15.4% during placebo treatment. The study was abandoned after two patients entered the 750 microg cohort due to a sustained systolic blood pressure response. Although this study was underpowered for the confirmation of efficacy, some indications of greater pain relief after 500 microg CNS 5161 compared with placebo could be observed (change in VAS between baseline and 12 h 10 +/- 22 mm vs. 2 +/- 19 mm; P = 0.11). CONCLUSIONS: CNS 5161 HCl was reasonably well tolerated up to 500 microg. The most common adverse events were hypertension, headache and mild visual disorders.

Antibody responses induced by long-term vaccination with an octovalent conjugate Pseudomonas aeruginosa vaccine in children with cystic fibrosis.

We assessed the serological responses over 10 years to repeated immunization of cystic fibrosis (CF) patients with an O-polysaccharide (OPS)-toxin A conjugate vaccine against Pseudomonas aeruginosa. A retrospective analysis was performed with sera from 25 vaccinated and 25 unvaccinated children treated at the same CF centre and matched for clinical management, age and gender. Yearly immunization led to sustained elevations of serum immunoglobulin G (IgG) antibody levels to all vaccine components. Eighteen unvaccinated patients but only eight vaccinated ones developed chronic pseudomonal lung infections. Infection rapidly caused further marked elevations of polysaccharide- but not toxin A-specific serum IgG in both immunized and nonimmunized patients, indicating that protection did not depend on the quantity of IgG present. However, qualitative analyses revealed that the protective capacity of specific serum IgG antibodies was linked to high affinity and to specificity for OPS serotypes rather than for lipopolysaccharide core epitopes.

Intranasal immunisation with conjugate vaccine protects mice from systemic and respiratory tract infection with Pseudomonas aeruginosa.

We tested intranasal application of anti-Pseudomonas conjugate vaccine in mice. Comparison of immunisation via the intra-muscular versus intranasal routes showed the induction of equivalent levels of specific serum IgG and IgG subclasses antibodies if cholera toxin was used as an adjuvant. In contrast, secretion of specific mucosal IgA antibodies in the upper respiratory tract was only observed after intranasal immunisation together with adjuvant. Systemic and mucosal immunity was also established via the intranasal route when CpG-containing oligonucleotides were used as adjuvant. The functionality of intranasally induced antibodies was proven in vitro by opsonophagocytosis and in vivo using the burn-wound sepsis and intra-tracheal lung infection models. These results demonstrate the feasibility of intranasal immunisation against P. aeruginosa with conjugate vaccine.

Electro-membrane microcurrent therapy reduces signs and symptoms of muscle damage.

PURPOSE: Delayed onset muscle soreness (DOMS) occurs after unaccustomed physical activity or competitive sport, resulting in stiff, painful muscles with impaired function. Acustat electro-membrane microcurrent therapy has been used to treat postoperative pain and soft tissue injury; however, its efficacy in reducing symptoms of muscle damage is not known. METHODS: Thirty healthy men were recruited for a double-blind, placebo-controlled trial. The muscles of their nondominant arms were damaged using an eccentric-exercise protocol. Subjects were then randomly assigned to treatment with either Acustat or a matching placebo membrane for 96 h and monitored for a total of 168 h. RESULTS: Subjects in both groups experienced severe pain and swelling of the elbow flexors after the eccentric exercise. After 24 h, the elbow joint angle of the placebo group had increased significantly more than those in the Acustat group (13.7 +/- 8.9 degrees vs 7.5 +/- 5.5 degrees; placebo vs Acustat, P < 0.05), possibly as a consequence of the elbow flexor muscles shortening. For the first 48 h after exercise, maximum voluntary contraction of the elbow flexor muscles was significantly impaired in the placebo group by up to 25% (P < 0.05), whereas muscle function was unchanged in the Acustat group. Peak plasma creatine kinase activity was also lower in the Acustat group (peak = 777 +/- 1438 U.L-1) versus the placebo group (peak = 1918 +/- 2067 U.L-1; (P < 0.05). The membranes were well tolerated by the subjects in both groups without any adverse effects. CONCLUSION: These data show that treatment of muscle damage with Acustat electro-membrane microcurrent therapy reduces the severity of the symptoms. The mechanisms of action are unknown but are likely related to maintenance of intracellular Ca2+ homeostasis after muscle damaging exercise.