Screening and surveillance recommendations for central nervous system hemangioblastomas in pediatric patients with Von Hippel-Lindau disease.

PURPOSE: Von Hippel-Lindau (VHL) disease is an autosomal-dominantly inherited tumor predisposition syndrome. One of the most common tumors are central nervous system (CNS) hemangioblastomas. Recommendations on the initiation and continuation of the screening and surveillance program for CNS tumors in pediatric VHL patients are based on small case series and thus low evidence level. To derive more robust screening recommendations, we report on the largest monocentric pediatric cohort of VHL patients. METHODS: We performed a retrospective analysis on a pediatric cohort of 99 VHL patients consulted at our VHL center from 1992 to 2023. Clinical, surgical, genetic, and imaging data were collected and statistically analyzed. RESULTS: 42 patients (50% male) developed CNS hemangioblastomas, of whom 18 patients (56% male) underwent hemangioblastoma surgery (mean age at first surgery: 14.9 ± 1.9 years; range 10.2-17). The first asymptomatic patient was operated on at the age of 13.2 years due to tumor progress. Truncating VHL mutation carriers had a significantly higher manifestation rate (HR = 3.7, 95% CI: 1.9-7.4, p < 0.0001) and surgery rate (HR = 3.3, 95% CI: 1.2-8.9, p = 0.02) compared with missense mutation carriers. CONCLUSION: We recommend starting MRI imaging at the age of 12 years with examination intervals every (1-) 2 years depending on CNS involvement. Special attention should be paid to patients with truncating variants. Affected families should be educated regularly on potential tumor-associated symptoms to enable timely MRI imaging and eventually intervention, as CNS hemangioblastoma may develop before screening begins. GERMAN CLINICAL TRIALS REGISTER REGISTRATION NUMBER: DRKS00029553, date of registration 08/16/2022, retrospectively registered.

Technical report: surgical preparation of human brain tissue for clinical and basic research.

BACKGROUND: The study of the distinct structure and function of the human central nervous system, both in healthy and diseased states, is becoming increasingly significant in the field of neuroscience. Typically, cortical and subcortical tissue is discarded during surgeries for tumors and epilepsy. Yet, there is a strong encouragement to utilize this tissue for clinical and basic research in humans. Here, we describe the technical aspects of the microdissection and immediate handling of viable human cortical access tissue for basic and clinical research, highlighting the measures needed to be taken in the operating room to ensure standardized procedures and optimal experimental results. METHODS: In multiple rounds of experiments (n = 36), we developed and refined surgical principles for the removal of cortical access tissue. The specimens were immediately immersed in cold carbogenated N-methyl-D-glucamine-based artificial cerebrospinal fluid for electrophysiology and electron microscopy experiments or specialized hibernation medium for organotypic slice cultures. RESULTS: The surgical principles of brain tissue microdissection were (1) rapid preparation (<1 min), (2) maintenance of the cortical axis, (3) minimization of mechanical trauma to sample, (4) use of pointed scalpel blade, (5) avoidance of cauterization and blunt preparation, (6) constant irrigation, and (7) retrieval of the sample without the use of forceps or suction. After a single round of introduction to these principles, multiple surgeons adopted the technique for samples with a minimal dimension of 5 mm spanning all cortical layers and subcortical white matter. Small samples (5-7 mm) were ideal for acute slice preparation and electrophysiology. No adverse events from sample resection were observed. CONCLUSION: The microdissection technique of human cortical access tissue is safe and easily adoptable into the routine of neurosurgical procedures. The standardized and reliable surgical extraction of human brain tissue lays the foundation for human-to-human translational research on human brain tissue.

Vertebral osteomyelitis in patients with Staphylococcus aureus bloodstream infection: Evaluation of risk factors for treatment failure.

OBJECTIVES: Staphylococcus aureus is the most common cause of pyogenic vertebral osteomyelitis (VO). Studies indicate that S. aureus VO results in poor outcome. We aimed to investigate risk factors for treatment failure in patients with Staphylococcus aureus bloodstream infection (SAB) and VO. METHODS: We conducted a post hoc-analysis of data from a German bi-center prospective SAB cohort (2006-2014). Patients were followed-up for one year. Primary outcome was treatment failure defined as relapse and/or death within one year. RESULTS: A total of 1069 patients with SAB were analyzed, with 92 VO patients. In addition to antibiotic treatment, surgery was performed in 60/92 patients. Treatment failed in 44/92 patients (death, n = 42; relapse, n = 2). Multivariable analysis revealed higher age (HR 1.04 [per year], 95%CI 1.01-1.07), Charlson comorbidity index (HR 1.20, 95%CI 1.06-1.36), presence of neurologic deficits (HR 2.53, 95%CI 1.15-5.53) and local abscess formation (HR 3.35, 95%CI 1.39-8.04) as independent risk factors for treatment failure. In contrast, surgery seemed to be associated with a favourable outcome (HR 0.45 (95%CI 0.20-0.997)). CONCLUSION: SAB patients with VO exhibit a high treatment failure rate. Red flags are older age, comorbidities, neurologic deficits and local abscess formation. Whether these patients benefit from intensified treatment (e.g. radical surgery, prolongation of antibiotics) should be investigated further.

Piezosurgery for safe and efficient petrous bone cutting in cerebellopontine angle and petroclival meningioma surgery.

Intradural petrous bone drilling has become a widespread practice, providing extended exposure in the removal of cerebellopontine angle (CPA) or petroclival tumors. Adjacent neurovascular structures are at risk, however, when drilling is performed in this deep and narrow area. Hence, this study evaluates the use of Piezosurgery (PS) as a non-rotating tool for selective bone cutting in CPA surgery. A Piezosurgery® device was used in 36 patients who underwent microsurgery for extra-axial CPA or petroclival tumors in our Neurosurgical Department between 2013 and 2019. The clinical and radiological data were retrospectively analyzed. The use of PS was evaluated with respect to the intraoperative applicability and limitations as well as efficacy and safety of the procedure. Piezosurgical petrous bone cutting was successfully performed in the removal of meningiomas or extra-axial metastases arising from the dura of the petroclival region (21 patients) or petrous bone (15 patients). PS proved to be very helpful in the deep and narrow CPA region, considerably reducing the surgeon's distress toward bone removal in close proximity to cranial nerves and vessels in comparison to common rotating drills. The use of PS was safe without injuries to neurovascular structures. Gross total resection was achieved in 67% of petroclival and 100% of petrous bone tumors. Piezosurgery proved to be an effective and safe method for selective petrous bone cutting in CPA surgery avoiding rotating power and associated risks. This technique can particularly be recommended for bone cutting in close vicinity to critical neurovascular structures.

A High Frequency of HIV-Specific Circulating Follicular Helper T Cells Is Associated with Preserved Memory B Cell Responses in HIV Controllers.

Follicular helper T cells (Tfh) play an essential role in the affinity maturation of the antibody response by providing help to B cells. To determine whether this CD4+ T cell subset may contribute to the spontaneous control of HIV infection, we analyzed the phenotype and function of circulating Tfh (cTfh) in patients from the ANRS CO21 CODEX cohort who naturally controlled HIV-1 replication to undetectable levels and compared them to treated patients with similarly low viral loads. HIV-specific cTfh (Tet+), detected by Gag-major histocompatibility complex class II (MHC-II) tetramer labeling in the CD45RA- CXCR5+ CD4+ T cell population, proved more frequent in the controller group (P = 0.002). The frequency of PD-1 expression in Tet+ cTfh was increased in both groups (median, >75%) compared to total cTfh (<30%), but the intensity of PD-1 expression per cell remained higher in the treated patient group (P = 0.02), pointing to the persistence of abnormal immune activation in treated patients. The function of cTfh, analyzed by the capacity to promote IgG secretion in cocultures with autologous memory B cells, did not show major differences between groups in terms of total IgG production but proved significantly more efficient in the controller group when measuring HIV-specific IgG production. The frequency of Tet+ cTfh correlated with HIV-specific IgG production (R = 0.71 for Gag-specific and R = 0.79 for Env-specific IgG, respectively). Taken together, our findings indicate that key cTfh-B cell interactions are preserved in controlled HIV infection, resulting in potent memory B cell responses that may play an underappreciated role in HIV control.IMPORTANCE The rare patients who spontaneously control HIV replication in the absence of therapy provide a unique model to identify determinants of an effective anti-HIV immune response. HIV controllers show signs of particularly efficient antiviral T cell responses, while their humoral response was until recently considered to play only a minor role in viral control. However, emerging evidence suggests that HIV controllers maintain a significant but "silent" antiviral memory B cell population that can be reactivated upon antigenic stimulation. We report that cTfh help likely contributes to the persistence of controller memory B cell responses, as the frequency of HIV-specific cTfh correlated with the induction of HIV-specific antibodies in functional assays. These findings suggest that T follicular help may contribute to HIV control and highlight the need for inducing such help in HIV vaccine strategies that aim at eliciting persistent B cell responses.

First experience using navigation-guided radiofrequency kyphoplasty for sacroplasty in sacral insufficiency fractures.

PURPOSE: To evaluate the efficacy and safety of navigation-guided radiofrequency kyphoplasty for sacroplasty in patients with sacral insufficiency fractures. METHODS: In this single-center retrospective observational study, four consecutive patients with sacral insufficiency fractures were treated with navigation-guided radiofrequency kyphoplasty for sacroplasty between April 2010 and May 2012. Symptom characteristics, pain duration and pain intensity were recorded for each patient. Cement extravasation was evaluated in thin-sliced and triplanar reconstructed CT scans of the sacrum. RESULTS: Four female patients with painful sacral insufficiency fractures and extensive osteopenic areas significantly improved from an average pre-treatment VAS score of 8.3 ± 0.5 to 2.3 ± 1.0 (p < 0.001) on the first postoperative day and to 1.3 ± 1.9 (p < 0.004) at follow-up (mean, 20.1 weeks). Slight cement extravasations were observed without evidence of being symptomatic. No major complications or procedure-related morbidity were noted. CONCLUSION: From the limited experience in four patients, navigation-guided radiofrequency kyphoplasty appears to be a safe and effective treatment option for sacral insufficiency fractures even though asymptomatic cement extravasation was noted. The use of navigation based on intraoperative 3 D images simplifies the positioning of the navigated bone needles via the long axis approach. The radiofrequency kyphoplasty system provides the possibility to administer a sufficient amount of bone cement with a well-defined viscosity over the entire period of the procedure leading to high security and low cement extravasation. Sacroplasty provides rapid and enduring pain relief and facilitates prompt mobilization.

Vesselplasty: a new minimally invasive approach to treat pathological vertebral fractures in selected tumor patients - preliminary results.

PURPOSE: To evaluate the effectiveness and safety of percutaneous vesselplasty in pathological vertebral fractures of the thoracolumbar spine in selected tumor patients. MATERIALS AND METHODS: Eleven pathological vertebral fractures in nine patients were treated with vesselplasty (Vessel-X®, MAXXSPINE). Nine of eleven vertebras (81.8 %) had major posterior wall deficiency (> 30 %). Clinical and radiological (CT) measures were obtained before and 3 months after the procedure. RESULTS: The mean VAS improved significantly from preoperative to postoperative (6.9 ± 2.2 to 3.7 ± 2.3; p < 0.05), as did the ODI (59.7 %± 19.2 % to 40.3 %± 24.0 %; p < 0.05). The physical component summary of the SF-36 was significantly improved by the operation (19.2 ± 8.0 to 31.0 ± 16.5; p < 0.05). Symptomatic cement leakage or other operation-associated complications were not observed. Three patients were primarily treated with concomitant minimally invasive stabilization via fixateur interne. One patient had to undergo minimally invasive stabilization via fixateur interne 4 months after vesselplasty due to further collapse of the treated vertebral body. CONCLUSION: From these preliminary results, vesselplasty appears to be a treatment option worth considering in pathological vertebral fractures, even in the case of posterior wall deficiency. Selected tumor patients might benefit from vesselplasty as a minimally invasive procedure for stabilization of the fractured vertebra, pain control, and improvement in body function and quality of life. Long-term prospective studies with a larger sample size are required to validate these results.

Essentials and pitfalls in the treatment of CNS hemangioblastomas and von Hippel-Lindau disease.

Hemangioblastomas are rare CNS tumors, which are mostly located in the posterior fossa or spinal cord and occasionally in spinal nerves. They can occur sporadically or as a component tumor of von Hippel-Lindau (VHL) disease, an autosomal dominant tumor syndrome. The limited awareness of several pitfalls in the therapy of these rare lesions results in delayed or suboptimal treatment for many of these patients, especially those with VHL disease. The University of Freiburg serves as a reference center for patients with VHL disease and hemangioblastomas. The current therapeutic strategies for hemangioblastoma patients and typical pitfalls are presented here.

[Improvement in expiratory peak flow (PEF) of COPD patients due to "lung" sport for 12 months]. / Verbesserung des exspiratorischen Spitzenflusses (PEF) von COPD-Patienten durch Lungensport über 12 Monate.

This prospective, randomised, controlled study deals with the question whether it is possible to induce an improvement of peak expiratory flow (PEF) in patients suffering from COPD by a structured "lung" sport programme over a longer period of time (12 months). Furthermore, a comparison with the spontaneous course of the disease was performed. A group of 7 COPD patients (1 man, 6 women, mean age 70 years, COPD grade II - III according to GOLD) who regularly took part in a structured lung sport programme was compared with a control group of 10 COPD patients (5 men, 5 women, mean age 67.5 years, COPD grade II - III according to GOLD) who denied doing sport. The PEF values of the patients were measured after 0 and 12 months during exacerbation-free intervals. The relative changes of PEF in percent after one year were statistically compared. There was an improvement of PEF of about + 10.4 % (standard deviation SD +/- 8.9 %) after 12 months of lung sport. The spontaneous course of the disease of the patients who denied doing sport led to a decrease of PEF of about - 8.8 % (standard deviation SD +/- 11.5 %). The difference in PEF changes with respect to "lung" sport and to the spontaneous course of COPD was highly significant (p < 0.01) in spite of a high standard deviation. The long lasting improvement of PEF due to sport among COPD patients speaks in favour of a positive effect of "lung" sport.

Peak expiratory flow as a predictor for the effectiveness of sport for patients with COPD.

This study intended to find simple parameters that were able to determine the increase in physical performance as a result of sport in a group of patients with COPD (lung sport). We regularly investigated pulse, oxygenation and peak expiratory flow in participants with COPD of a "lung sport group", who participated in a structured weekly training program under professional supervision. Ten volunteers (7 females, 3 males, median of age = 69) with COPD (grade II-III) took part in the study. - The relative changes after 3 and 6 months were compared with the values of the first month of exercise. Measurements were carried out before exercise, after stamina training and at the end of the program. - Pulse and oxygenation did not show any changes. However, there was a significant improvement of peak flow after 6 months. - These peak flow changes represent further evidence of positive effects of sport in COPD and provide a parameter which allows the patients themselves to measure and evaluate the success of their physical activity.

Resistance gene homologues in melon are linked to genetic loci conferring disease and pest resistance.

Genomic and cDNA fragments with homology to known disease resistance genes (RGH fragments) were cloned from Cucumis melo using degenerate-primer PCR. Fifteen homologues of the NBS-LRR gene family have been isolated. The NBS-LRR homologues show high divergence and, based on the partial NBS-fragment sequences, appear to include members of the two major subfamilies that have been described in dicot plants, one that possesses a TIR-protein element and one that lacks such a domain. Genomic organization of these sequences was explored by DNA gel-blot analysis, and conservation among other Cucurbitaceae was assessed. Two mapping populations that segregate for several disease and pest resistance loci were used to map the RGH probes onto the melon genetic map. Several NBS-LRR related sequences mapped to the vicinity of genetic loci that control resistance to papaya ringspot virus, Fusarium oxysporum race 1, F. oxysporum race 2 and to the insect pest Aphis gossypii. The utility of such markers for breeding resistant melon cultivars and for cloning the respective R-genes is discussed.

Limb sparing surgery for vulvar groin recurrence: a case report and review of the literature.

Hemipelvectomy was successfully avoided in a patient with extensive necrotic groin recurrence of vulvar cancer after prior radiation therapy. Tumor-free resection margins were achieved by wide excision of the recurrence including resection of the pubic bone and adjacent muscles. After resection of the femoral artery, blood supply to the leg was restored by an extra-anatomic axillopopliteal bypass. A myocutaneous flap from the contralateral rectus abdominis was used for primary wound closure. Limb salvage was achieved and the patient experienced pain relief, excellent cosmesis, and independent gait. Aspects of treatment options, even though primarily palliative, in groin recurrence of vulvar carcinoma are discussed.

[Sensomotor function while wearing lumbar support ortheses]. / Sensomotorik beim Tragen lumbaler Stützorthesen.

AIM: Flexible lumbar corsets should contribute to an improved active and passive stabilisation of the lumbar spine. In the present study, the effects of flexible corsets on sensory-motor abilities have been investigated. METHODS: 24 healthy subjects (m = 10, f = 14, 26.7 years) performed angle- and force-reproduction tasks with and without wearing a flexible corset. The subjects tried to reproduce trunk flexion angles of 20 degrees und 40 degrees as well as forces of 33% and 66% of the maximum strength of the back extensor muscles. Additionally, muscular reactions were measured during destabilizing stimuli. RESULTS: No significant differences were found for the reproduction tasks. When wearing the corset, the left erector spinae muscles showed a delayed onset (+15 ms, p < 0.05), and the obliquus abdominis reached maximal activity more rapidly (-18 ms, p < 0.05). In the preinnervation phase the obliquus abdominis (-33%, p < 0.01), in the eccentric phase the erector spinae (-27%, p < 0.05) and the right obliquus abdominis (-46%, p < 0.05) and in the concentric phase the right obliquus abdominis (-35%, p < 0.01) and the rectus abdominis (-32%, p < 0.05) showed lower activities. CONCLUSION: The reduced muscle activities with destabilizing stimuli can be interpreted as the result of an improved passive stabilisation of the lumbar region by wearing a flexible corset.

Site-specific interaction of thrombin and inhibitors observed by fluorescence correlation spectroscopy.

We report on the application of fluorescence correlation spectroscopy (FCS) to observe the interaction between thrombin and thrombin inhibitors. Two site-specific fluorescent labels were used to distinguish between inhibitors directed to the active site, the exosite, or both binding sites of thrombin. For several well-known inhibitors of thrombin, the binding sites observed by FCS correspond to previous studies. The interaction of the recently discovered thrombin inhibitor ornithodorin from the tick Ornithodorus moubata with thrombin was investigated. It was found that this inhibitor, like hirudin and rhodniin, binds to both the active site and exosite of thrombin simultaneously. This study shows the feasibility of FCS as a sensitive and selective method for observing protein-ligand interactions. As an additional technique, simultaneous labeling with both fluorescent labels was successfully demonstrated.

N-proximal sequence motif in light-harvesting chlorophyll a/b-binding protein is essential for the trimerization of light-harvesting chlorophyll a/b complex.

The major light-harvesting complex (LHCII) of photosystem II can be reconstituted in its native, trimeric form starting from its apoprotein light-harvesting chlorophyll a/b-binding protein (LHCP), pigments, and thylakoid lipids. In this paper we identify segments in the LHCP polypeptide that are essential for the formation of stable LHCII trimers by analyzing N- and C-terminal deletion mutants of LHCP and mutants carrying point-specific amino acid exchanges. C-terminal deletions that do not abolish pigment binding to LHCP do not affect trimerization either. By contrast, on the N-terminus of LHCP, where as many as 61 amino acids can be deleted without significant effects on pigment binding, only 15 amino acids are dispensible for LHCII trimer formation. This indicates that structural elements between amino acids 16 and 61 are involved in the stabilization of LHCII trimers but not monomers. Closer inspection of this protein domain in a more detailed mutation analysis revealed that amino acids W16 and/or Y17 as well as R21 are essential for the formation of LHCII trimers. These amino acids are conserved in virtually all known sequences of LHCII apoproteins but only in some of the minor chlorophyll a/b complexes. Possible functions of the crucial residues are discussed.

[School and child health]. / Die Schule und die Gesundheit des Kindes.

A roundtable discussion involving 2 educators and 4 pediatricians with widely varying experience sounded out the negative (pathogenic) and positive (healthy) influences to which a child is exposed in school and which decisively shape his/her physical, mental and psychic development. Concrete case reports and a systematic compilation of harmful factors show that this institution poses major threats to children's health of which pediatricians should be aware. An important cause of childhood suffering is the discrepancy between the uniform and inflexible institutional structures and the variability of children's needs conditioned by biology and social origin. Between ideal visions and the consequent school structures on the one hand, and social reality on the other hand, there are notable contradictions which must be recognized, lived with and--if possible--resolved by reforms. If he believes in the reformability of school, the pediatrician can make essential contribution to promoting health during school age.

Electric field-induced concentration gradients in lipid monolayers.

Externally applied electric field gradients gave rise to lateral concentration gradients in monolayers of certain binary lipid mixtures. For binary mixtures of dihydrocholesterol and dimyristoylphosphatidylcholine, the application of an electric field gradient at pressures below the critical pressure produced a liquid-liquid phase separation in a monolayer that is otherwise homogenous. At pressures slightly above the critical pressure, a field gradient produced a large concentration gradient without phase separation. The lipid concentration gradients can be described by equilibrium thermodynamic chemical potentials. The observed effects appear to be relevant to the structure and composition of biological membranes.

Cardiology education using hypermedia and digital imagery.

A computer-based educational system for the study of cardiovascular imaging is described. This system, based on HyperCard * and a standard Macintosh II, integrates hypertext retrieval, computer graphics, sound, and medical images into a single interactive environment stored on a standard hard disk. This 'hypermedia' approach allows arbitrary complexity coupled with direct, immediate, easy traversal of the images and related text, which provides the opportunity for students to move at their own pace, choose their own direction through the material and repeat as often as desired. Storage on magnetic medium allows for easy updating with new studies and material in order to keep pace with advances in medical imaging technology. The system could be mastered onto CD-ROM for ease of distribution if so desired. The system includes a tutorial on the basics of digital image representation and example studies from cineangiography, nuclear medicine, echocardiography and magnetic resonance imaging of the heart. Quantitative techniques for evaluation of left ventricular function are explained using computer graphics overlays on the original medical images. Color encoded functional images are also included as an aid to visualization of ventricular performance data. The system has proven useful as a primer for digital imaging in cardiology prior to specific case study in a traditional mentor relationship.

Evaluation of the Biolog automated microbial identification system.

Biolog's identification system was used to identify 39 American Type Culture Collection reference taxa and 45 gram-negative isolates from water samples. Of the reference strains, 98% were identified to genus level and 76% to species level within 4 to 24 h. Identification of some authentic strains of Enterobacter, Klebsiella, and Serratia was unreliable. A total of 93% of the water isolates were identified.