Intraoperative radiotherapy combined with spinal stabilization surgery-a novel treatment strategy for spinal metastases based on a first single-center experiences.

INTRODUCTION: Current treatment of spinal metastases (SM) aims on preserving spinal stability, neurological status, and functional status as well as achieving local control. It consists of spinal surgery followed by radiotherapy and/or systemic treatment. Adjuvant therapy usually starts with a delay of a few weeks to prevent wound healing issues. Intraoperative radiotherapy (IORT) has previously been successfully applied during brain tumor, breast and colorectal carcinoma surgery but not in SM, including unstable one, to date. In our case series, we describe the feasibility, morbidity and mortality of a novel treatment protocol for SM combining stabilization surgery with IORT. METHODS: Single center case series on patients with SM. Single session stabilization by navigated open or percutaneous procedure using a carbon screw-rod system followed by concurrent 50 kV photon-IORT (ZEISS Intrabeam). The IORT probe is placed via a guide canula using navigation, positioning is controlled by IOCT or 3D-fluroscopy enabling RT isodose planning in the OR. RESULTS: 15 (8 female) patients (71 ± 10y) received this treatment between 07/22 and 09/23. Median Spinal Neoplastic Instability Score was 8 [7-10] IQR. Most metastasis were located in the thoracic (n = 11, 73.3%) and the rest in the lumbar (n = 4, 26.7%) spine. 9 (60%) patients received open, 5 (33%) percutaneous stabilization and 1 (7%) decompression only. Mean length of surgery was 157 ± 45 min. Eleven patients had 8 and 3 had 4 screws placed. In 2 patients radiotherapy was not completed due to bending of the guide canula with consecutive abortion of IORT. All other patients received 8 Gy isodoses at mdn. 1.5 cm [1.1-1.9, IQR] depth during 2-6 min. The patients had Epidural Spinal Cord Compression score 1a-3. Seven patients (46.7%) experienced adverse events including 2 surgical site infection (one 65 days after surgery). CONCLUSION: 50 kV photon IORT for SM and consecutive unstable spine needing surgical intervention is safe and feasible and can be a promising technique in selected cases.

Intraoperative radiotherapy during awake craniotomies: preliminary results of a single-center case series.

Awake craniotomies are performed to avoid postoperative neurological deficits when resecting lesions in the eloquent cortex, especially the speech area. Intraoperative radiotherapy (IORT) has recently focused on optimizing the oncological treatment of primary malignant brain tumors and metastases. Herein, for the first time, we present preliminary results of IORT in the setting of awake craniotomies. From 2021 to 2022, all patients undergoing awake craniotomies for tumor resection combined with IORT were analyzed retrospectively. Demographical and clinical data, operative procedure, and treatment-related complications were evaluated. Five patients were identified (age (mean ± standard deviation (SD): 65 ± 13.5 years (y)). A solid left frontal metastasis was detected in the first patient (female, 49 y). The second patient (male, 72 y) presented with a solid metastasis on the left parietal lobe. The third patient (male, 52 y) was diagnosed with a left temporoparietal metastasis. Patient four (male, 74 y) was diagnosed with a high-grade glioma on the left frontal lobe. A metastasis on the left temporooccipital lobe was detected in the fifth patient (male, 78 y). After awake craniotomy and macroscopic complete tumor resection, intraoperative tumor bed irradiation was carried out with 50 kV x-rays and a total of 20 Gy for 16.7 ± 2.5 min. During a mean follow-up of 6.3 ± 2.6 months, none of the patients developed any surgery- or IORT-related complications or disabling permanent neurological deficits. Intraoperative radiotherapy in combination with awake craniotomy seems to be feasible and safe.

[Acupuncture techniques in professional football]. / Akupunkturtechniken im Profifußball.

The number of scientific studies about acupuncture has increased significantly during recent years. Acupuncture can be used as an evidence-based adjunct therapy for a variety of indications in professional football. This review summarizes various acupuncture techniques and related techniques for utilization in the field of professional soccer. Besides knee, shoulder, spinal, elbow and postoperative pain, scientific meta-analyses also point towards the effectiveness of acupuncture in ankle sprains, allergic rhinoconjunctivitis and nausea. Dry needling is an emerging option for treatment of myofascial trigger points and could potentially result in improved prevention of muscular injuries and enhancement of muscular performance.

Consensus statement on prevention and management of adverse effects following rejuvenation procedures with hyaluronic acid-based fillers.

Facial fillers play an important role in the correction of facial changes associated with ageing. They offer quick treatments in the outpatient setting with minimal subsequent downtime that provide predictable, natural-looking, long-lasting results. Adverse reactions after hyaluronic acid injections tend to be mild or moderate and rather temporary. However, as with all injected or implanted biomaterials, severe adverse events can occur and patients must be fully informed of potential risks prior to undergoing treatment. A panel of experts from Germany (D), Austria (A) and Switzerland (CH) developed recommendations, and this study provides the 'DACH Consensus Recommendations' from this group specifically on the use of hyaluronic acid fillers. The aim is to help clinicians recognize potential risks and to provide guidance on how best to treat adverse events if they arise. Contraindications to hyaluronic acid fillers are also detailed, and ways to prevent adverse events occurring are discussed. Hyaluronic acid-based products are claimed to be very close to an ideal tissue augmentation agent; nevertheless, profound medical, anatomical and product knowledge are of paramount importance to minimize the occurrence of adverse reactions.

Clinical and surgical outcome in patients with cervical spondylodiscitis-a single-center retrospective case series of 24 patients.

Objective: Cervical spondylodiscitis is a rare pathology, with an incidence of 0.5-2.5 per 100,000 population, posing significant potential risks. This type of infection can lead to neurological impairment in up to 29% of patients. Radical surgical debridement of the infected segment, fusion, and an intravenous antibiotic regimen remains the gold standard in most spine centers. This study aimed to analyze the surgical outcome in a tertiary spine center based on disease severity. Methods: In this study, we retrospectively included all patients diagnosed with cervical spondylodiscitis and treated at the University Hospital Augsburg between January 2017 and May 2022. We collected and analyzed baseline parameters on clinical presentation with symptoms, laboratory parameters, radiological appearance, and surgical parameters such as type of approach and implant, as well as neurological and radiological outcomes. Descriptive statistics were performed using SPSS, and relevant correlations were examined using the t-test for independent samples and the chi-square test. Results: Twenty-four patients (9%) with cervical spondylodiscitis were identified. Twenty-two (92%) surgically treated patients were subdivided into the complicated discitis group (n = 14, 64%) and the uncomplicated discitis group (n = 8, 36%). Seventeen patients (71%) presented with sepsis on admission, 17 patients (71%) were diagnosed with epidural abscess on primary imaging, and 5 patients (21%) had more than one discitis lesion at a distant spinal segment. The presence of epidural abscess was significantly associated with systemic sepsis (OR = 6.2; p = 0.03) and myelopathy symptoms (OR = 14.4; p = 0.00). The most frequently detected specimen was a multisensitive Staphylococcus aureus (10 patients, 42%). Six patients (25%) died after a median of 20 days despite antibiogram-accurate therapy, five of whom were diagnosed with a complicated type of discitis. The follow-up data of 15 patients (63%) revealed permanent neurological damage in 9 patients (38%). Notably, the surgical approach was a significant factor for revision surgery (p = 0.008), as three out of five (60%) ventrodorsal cases with complicated discitis were revised. Conclusion: Cervical spondylodiscitis represents a severe infectious disease that is often associated with permanent neurological damage or a fatal outcome, despite adequate surgical and antibiotic treatments. Complicated types of discitis may require a more challenging surgical and clinical course.

Usability of a visual feedback system to assess and improve movement disorders related to neck pain: Perceptions of physical therapists and patients.

A prototype visual feedback system has been developed to assess and improve movement disorders related to neck pain. The aim of this study was to assess the usability of the prototype in a rehabilitation setting. Twelve physical therapists integrated the device into their regular therapy programs for 24 neck pain patients with movement disorders. Each patient performed three individual therapy sessions with the device under physical therapist supervision. Usability was assessed by the physical therapists and patients using therapy diaries, the System Usability Scale, and focus group or personal interviews. Based on an overall usability rating of marginally acceptable, the visual feedback system was generally found to be a device with the potential to assess and train neck pain patients but needs improvement. To become a useful adjunct to regular physical therapy, improvements in the hardware and software, and further system developments are required.

Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice.

The resilience and strength of bone is due to the orderly mineralization of a specialized extracellular matrix (ECM) composed of type I collagen (90%) and a host of non-collagenous proteins that are, in general, also found in other tissues. Biglycan (encoded by the gene Bgn) is an ECM proteoglycan that is enriched in bone and other non-skeletal connective tissues. In vitro studies indicate that Bgn may function in connective tissue metabolism by binding to collagen fibrils and TGF-beta (refs 5,6), and may promote neuronal survival. To study the role of Bgn in vivo, we generated Bgn-deficient mice. Although apparently normal at birth, these mice display a phenotype characterized by a reduced growth rate and decreased bone mass due to the absence of Bgn. To our knowledge, this is the first report in which deficiency of a non-collagenous ECM protein leads to a skeletal phenotype that is marked by low bone mass that becomes more obvious with age. These mice may serve as an animal model to study the role of ECM proteins in osteoporosis.

Oxidative stress and lung injury induced by short-term exposure to wood smoke in guinea pigs.

Oxidative stress and lung injury induced by short-term exposure to wood smoke were evaluated in guinea pigs through cell profile, bronchoalveolar lavage (BAL), conventional histology and immunohistochemistry (4-hydroxynonenal, 3-nitrotyrosine, Mn-superoxide dismutase, heme oxygenase-1); malondialdehyde and 4-hydroxynonenal concentration, Mn-superoxide dismutase, glutathione reductase, glutathione peroxidase, and catalase activities in plasma, lung and BAL. Total cells increased in BAL, and the percentage of macrophages, neutrophils and lymphocytes augmented (72-96 h). Histopathological examination of lung tissues showed mild thickening of membranous bronchiole walls, infiltration of foamy macrophages and polymorphonuclear leukocytes in bronchial, bronchiolar and intraalveolar spaces. Goblet cell hyperplasia was also observed in bronchial and bronchiolar epithelia. Plasma malondialdehyde concentration was increased at all times, while 4-hydroxynonenal was increased only in plasma and BAL after 24 h. Plasma glutathione reductase activity increased at 24 and 72 h, BAL glutathione peroxidase activity decreased at 72 and 96 h, whereas catalase activity increased in plasma at 72 h, and decreased in BAL at 24 h. Immunostaining intensity to 4-hydroxynonenal, 3-nitrotyrosine, Mn-superoxide dismutase and heme oxygenase-1 was enhanced mainly in macrophages, bronchial/bronchiolar epithelial cells and type II pneumocytes after 72-96 h of wood smoke exposure. Overall, short-term exposure to wood smoke induces alterations in oxidative/antioxidant state in lung and airway injury, similar to those observed in humans with domestic exposure.

[Implementation of a palliative care concept in a geriatric acute care hospital]. / Die Implementierung eines Palliativkonzepts in ein geriatrisches Akutkrankenhaus.

To integrate palliative care patients into an acute geriatric ward requires extensive and continuous education and preparation of all participating professionals. It can be a lengthy process to integrate palliative care concepts despite cooperation of the hospital administration. The group of patients to be integrated differs from the patients of regular geriatric wards because of a higher percentage of relatively young oncologic patients and they differ from a regular palliative ward because about 50% are non-oncologic patients, while the average age is much higher than in normal palliative care. It is possible to integrate specialized palliative care into a regular geriatric ward. Patients admitted without palliative intention will benefit the most from ward-integrated palliative care if the treatment aim turns this way. Ward-integrated palliative care can be an integral part of treating geriatric patients in addition to acute geriatric medicine, rehabilitation, and prevention. It can also provide caretakers and patients with the benefits from continuity of treatment and care.

A family of AMPA-selective glutamate receptors.

Four cloned cDNAs encoding 900-amino acid putative glutamate receptors with approximately 70 percent sequence identity were isolated from a rat brain cDNA library. In situ hybridization revealed differential expression patterns of the cognate mRNAs throughout the brain. Functional expression of the cDNAs in cultured mammalian cells generated receptors displaying alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective binding pharmacology (AMPA = quisqualate greater than glutamate greater than kainate) as well as cation channels gated by glutamate, AMPA, and kainate and blocked by 6,7-dinitroquinoxaline-2,3-dione (CNQX).

Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS.

In the central nervous system (CNS), the principal mediators of fast synaptic excitatory neurotransmission are L-glutamate-gated ion channels that are responsive to the glutamate agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). In each member of a family of four abundant AMPA receptors, a small segment preceding the predicted fourth transmembrane region has been shown to exist in two versions with different amino acid sequences. These modules, designated "flip" and "flop," are encoded by adjacent exons of the receptor genes and impart different pharmacological and kinetic properties on currents evoked by L-glutamate or AMPA, but not those evoked by kainate. For each receptor, the alternatively spliced messenger RNAs show distinct expression patterns in rat brain, particularly in the CA1 and CA3 fields of the hippocampus. These results identify a switch in the molecular and functional properties of glutamate receptors operated by alternative splicing.

Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning.

Gene-targeted mice lacking the L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit GluR-A exhibited normal development, life expectancy, and fine structure of neuronal dendrites and synapses. In hippocampal CA1 pyramidal neurons, GluR-A-/- mice showed a reduction in functional AMPA receptors, with the remaining receptors preferentially targeted to synapses. Thus, the CA1 soma-patch currents were strongly reduced, but glutamatergic synaptic currents were unaltered; and evoked dendritic and spinous Ca2+ transients, Ca2+-dependent gene activation, and hippocampal field potentials were as in the wild type. In adult GluR-A-/- mice, associative long-term potentiation (LTP) was absent in CA3 to CA1 synapses, but spatial learning in the water maze was not impaired. The results suggest that CA1 hippocampal LTP is controlled by the number or subunit composition of AMPA receptors and show a dichotomy between LTP in CA1 and acquisition of spatial memory.

Amyloid beta interacts with the amyloid precursor protein: a potential toxic mechanism in Alzheimer's disease.

Amyloid beta protein (Abeta) deposition in the brain is a hallmark of Alzheimer's disease (AD). The fibrillar form of Abeta is neurotoxic, although the mechanism of its toxicity is unknown. We showed that conversion of Abeta to the fibrillar form markedly increased binding to specific neuronal membrane proteins, including amyloid precursor protein (APP). Nanomolar concentrations of fibrillar Abeta bound cell-surface holo-APP in cortical neurons. Reduced vulnerability of cultured APP-null neurons to Abeta neurotoxicity suggested that Abeta neurotoxicity involves APP. Thus Abeta toxicity may be mediated by the interaction of fibrillar Abeta with neuronal membrane proteins, notably APP. An Abeta-APP interaction reminiscent of the pathogenic mechanism of prions may thus contribute to neuronal degeneration in AD.

Surgical anatomy of the frontal recess--is there a benefit in multiplanar CT-reconstruction?

Anatomical variations in the sinus region are not necessarily pathological, but they may complicate the anatomy of the lateral nasal wall and contribute to the occurrence or persistence of chronic inflammatory diseases. In this study the interpretations of initial coronal CT scans were significantly altered following multiplanar CT-reconstruction. Assuming that a multiplanar analysis includes coronal views, we may conclude that imaging in three planes yields more information and provides a substantial benefit in the planning and performance of a surgical procedure on the paranasal sinuses.

Interaction between two different regulatory elements activates the murine alpha A-crystallin gene promoter in explanted lens epithelia.

Previous experiments have indicated that 5' flanking DNA sequences (nucleotides-366 to +46) are capable of regulating the lens-specific transcription of the murine alpha A-crystallin gene. Here we have analyzed these 5' regulatory sequences by transfecting explanted embryonic chicken lens epithelia with different alpha A-crystallin-CAT (chloramphenicol acetyltransferase) hybrid genes (alpha A-crystallin promoter sequences fused to the bacterial CAT gene in the pSVO-CAT expression vector). The results indicated the presence of a proximal (-88 to +46) and a distal (-111 to -88) domain which must interact for promoter function. Deletion experiments showed that the sequence between -88 and -60 was essential for function of the proximal domain in the explanted epithelia. A synthetic oligonucleotide containing the sequence between -111 and -84 activated the proximal domain when placed in either orientation 57 base pairs upstream from position -88 of the alpha A-crystallin-CAT hybrid gene.

[Bridging peripheral nerve defects by means of nerve conduits]. / Uberbrückung peripherer Nervendefekte durch den Einsatz von Nervenröhrchen.

BACKGROUND: The nerve autograft is the gold standard for the reconstruction of peripheral nerve defects. In short gaps, nerve repair by means of tubulization has become an alternative. This technique is discussed based on the current literature and our own experience. PATIENTS AND METHODS: Nerve reconstruction by means of tubulization was performed in 11 patients. Nerve gaps in the hand of up to 18 mm were reconstructed. Sensibility was assessed using static and dynamic two point discrimination (s-, d2PD) and monofilament testing 3, 6 and 12 months postoperatively. RESULTS: Three out of 11 patients complained of a temporary foreign body sensation in the area of the implant; this was persistent in one case. Four out of six patients showed excellent results with s2PD of 15 mm, S0), another poor sensibility (s2PD 15 mm, S3). D2PD and monofilament testing confirmed these results. CONCLUSIONS: Nerve reconstruction by means of tubulization seems to be a suitable method for certain indications in the reconstruction of short defects of digital and palmar nerves. Donor site morbidity can be avoided. Similarly to nerve transplantation, the operation requires microsurgical skills.

Molecular biology of glutamate receptors.

The ligand-gated receptors for L-glutamate play a central role in acute neuronal degeneration. Recently cDNAs have been isolated for subunits of several glutamate receptor subtypes. By sequence homology all these subunits clearly belong to one large gene family. Several subfamilies exist and match roughly previously pharmacologically and electrophysiologically defined subtypes of glutamate receptors. Currently four genes (GluR A, B, C and D) are known that code for the AMPA subtypes of glutamate receptors. Recombinant expression of wild type and mutated sequences identified a critical residue in the putative TM2 channel-lining segment that controls Ca2+ ion permeability. The arginine (R) found in GluR B subunits at that position renders AMPA channels impermeable for Ca2+ ions, whereas glutamine (Q) containing GluR A, C and D subunits give rise to Ca2+ permeable channels. RNA editing converts the genomically encoded glutamine codon into the arginine codon found in GluR B cDNAs for the Q/R site. NMDA subtypes of glutamate receptors are formed after coexpression of the NR1 cDNA with a cDNA of the NR2 family. Depending on the member of the NR2 family used, NMDA receptors with different kinetical and pharmacological properties are generated. Common to all channels of these NMDA receptors is a high permeability for Ca2+ ions and a voltage dependent block by Mg2+ ions. All currently known NMDA receptor subunits have an asparagine at the Q/R homologous position. We found that this residue is critical for Mg2+ block and Ca2+ permeability of NMDA receptor channels.

Cerebral amyloid induces aberrant axonal sprouting and ectopic terminal formation in amyloid precursor protein transgenic mice.

A characteristic feature of Alzheimer's disease (AD) is the formation of amyloid plaques in the brain. Although this hallmark pathology has been well described, the biological effects of plaques are poorly understood. To study the effect of amyloid plaques on axons and neuronal connectivity, we have examined the axonal projections from the entorhinal cortex in aged amyloid precursor protein (APP) transgenic mice that exhibit cerebral amyloid deposition in plaques and vessels (APP23 mice). Here we report that entorhinal axons form dystrophic boutons around amyloid plaques in the entorhinal termination zone of the hippocampus. More importantly, entorhinal boutons were found associated with amyloid in ectopic locations within the hippocampus, the thalamus, white matter tracts, as well as surrounding vascular amyloid. Many of these ectopic entorhinal boutons were immunopositive for the growth-associated protein GAP-43 and showed light and electron microscopic characteristics of axonal terminals. Our findings suggest that (1) cerebral amyloid deposition has neurotropic effects and is the main cause of aberrant sprouting in AD brain; (2) the magnitude and significance of sprouting in AD have been underestimated; and (3) cerebral amyloid leads to the disruption of neuronal connectivity which, in turn, may significantly contribute to AD dementia.

Glutamate receptor channels: novel properties and new clones.

Glutamate is the principal excitatory neurotransmitter in the brain. Glutamate activates cation-selective receptor channels carried by nearly every neuron and by glial cells. Bernd Sommer and Peter Seeburg describe how our concepts concerning the molecular and functional design of ionotropic glutamate receptors are rapidly progressing, with the recent discovery of novel receptor properties and new subunits following the landmark cloning of the first receptor subunit by M. Hollmann and his colleagues. New properties currently revealed by the cloned receptor channels may guide physiologists in characterizing the elementary steps in synaptic transmission, help neurologists to define the role of glutamate receptors in acute and chronic neuropathologies, and enlighten all neuroscientists whose models for learning and memory involve the idiosyncracies of particular channel subtypes.

Physiological and pharmacological stimulation of pancreatic islet hormone secretion in type I diabetic pancreas allograft recipients.

Successful heterotopic and denervated pancreas allograft transplantation (PAT) often results in normoglycemia and peripheral hyperinsulinemia in insulin-dependent (type I) diabetic recipients. The contribution of altered hepatic insulin extraction (HIE) to the resulting hyperinsulinemia in such patients remains uncertain. Furthermore, whether the denervated pancreas allografts exhibit beta-cell hyperresponsiveness to physiological and pharmacological stimulation is controversial. We evaluated beta-cell function and HIE after successful whole cadaveric PAT with systemic venous drainage in 13 type I diabetic patients before and after mixed-meal and intravenous glucose and glucagon administration. The results were compared with those of 5 nondiabetic patients with kidney transplantation only, who had native innervated pancreases with portal insulin delivery and were receiving an equivalent triple immunosuppressive therapy (cyclosporin, azathioprine, and prednisone), and 7 healthy control subjects with no family history of diabetes. After PAT, fasting and poststimulation serum glucose concentrations were normalized. PAT was associated with marked basal hyperinsulinemia (3- to 8-fold) as assessed by immunoreactive insulin (IRI) levels in type I diabetic patients (mean +/- SE 345 +/- 43 pM) compared with control subjects (43 +/- 14 pM) and nondiabetic kidney-transplantation patients (129 +/- 38 pM). After mixed-meal ingestion, the mean incremental integrated insulin area was similar in PAT patients (18 +/- 3 nM.min) compared with kidney-transplantation patients (20 +/- 4 nM.min) and healthy control subjects (21 +/- 3 nM.min). Basal serum C-peptide levels were significantly greater in PAT (1.72 +/- 0.13 nM) and kidney-transplantation (2.15 +/- 0.33 nM) patients than in healthy control subjects (0.50 +/- 0.10 nM; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)