Drug monitoring during ciprofloxacin prophylaxis of allogeneic stem cell transplant patients: associations with bacterial infections through a monocentric observational prospective study.

BACKGROUND: Bacterial infection ranks amongst the most common causes of morbidity and mortality in patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT). Although ciprofloxacin (CIP) prophylaxis is recommended, information on serum levels and clinical course is lacking. AIM: To investigate relationships between CIP level and failure of prophylaxis, particularly in terms of whether different pharmacokinetic (PK) indices [area under the concentration-time curve (AUC0-24h) vs single time samples] correlate differently with the outcome. METHODS: This prospective observational monocentric study was conducted at a 1500-bed teaching hospital (March 2018-March 2019), including 63 adult patients with alloHSCT receiving CIP prophylaxis. Blood samples were drawn at three sampling times (1, 6 and 12 h post-administration), twice per week, and measured via high performance liquid chromatography. The onset of febrile episodes (FEBs) indicated suspected failure of CIP prophylaxis. Positive blood cultures [bloodstream infection (BSI)] indicated confirmed failure of prophylaxis. FINDINGS: Seven of 63 patients died without significant differences in their average CIP levels compared with survivors, with patients experiencing FEBs (54/63) displaying a 13% [95% confidence interval (CI) 4-22%] lower probability of survival. In total, 225 sets of three values (triplets) were obtained from 58 primary CIP episodes. Triplets preceding BSI with Gram-negative bacteria (GNB-BSI) showed lower AUC0-24h on average, but similar single time sample indices. An AUC0-24h of ≤21.61 mgh/L resulted in four-fold higher odds of GNB-BSI (adjusted odds ratio 3.96, 95% CI 1.21-13.00). These results were independent of the administration route, patient demographics or sampling protocol deviations, indicating reduced CIP exposure upon GNB-BSI events. CONCLUSION: Monitoring CIP levels, using multiple sampling times, may be useful to reduce alloHSCT-associated bacterial infections. Further analysis is needed to investigate causality.

Neurosurgical treatment of pediatric brain tumors - results from a single center multidisciplinary setup.

OBJECTIVE: The challenge of pediatric brain tumor surgery is given due to a relative low prevalence but high heterogeneity in age, localization, and pathology. Improvements of long-term overall survival rates were achieved during the past decades stressing the importance of a multidisciplinary decision process guided by a national treatment protocol. We reviewed the entire spectrum of pediatric brain tumor surgeries from the perspective of an interdisciplinary pediatric neuro-oncology center in Germany. METHODS: Every patient who underwent brain tumor surgery from January 2010 to June 2017 in our Pediatric Neurosurgery department was retrospectively included and evaluated regarding the course of treatment. Perioperative data such as tumor localization, timing of surgery, extent of resection, neuropathological diagnosis, transfusion rates, oncologic and radiation therapy, and neurological follow-up including morbidity and mortality were evaluated. RESULTS: Two hundred ninety-three pediatric brain tumor patients were applicable (age: 8.28 ± 5.62 years, 1.22:1.0 m:f). A total of 531 tumor surgical interventions was performed within these patients (457 tumor resections, 74 tumor biopsies; mean interventions per patient 1.8 ± 1.2). Due to a critical neurologic status, 32 operations (6%) were performed on the day of admission. In 65.2% of all cases, tumor were approached supratentorially. Most frequent diagnoses of the cases were glial tumors (47.8%) and embryonal tumors (17.6%). Preoperative planned extent of resection was achieved in 92.7%. Pre- and postoperative neurologic deficits resolved completely in 30.7%, whereas symptom regressed in 28.6% of surgical interventions. New postoperative neurologic deficit was observed in 10.7%, which resolved or improved in 80% of these cases during 30 days. The mortality rate was 1%. CONCLUSION: We outlined the center perspective of a specialized pediatric neuro-oncological center describing the heterogeneous distribution of cases regarding age-related prevalence, tumor localization, and biology, which requires a high multidisciplinary expertise. The study contributes to define challenges in treating pediatric brain tumors and to develop quality indicators for pediatric neuro-oncological surgery. We assume that an adequate volume load of patients within a interdisciplinary infrastructure is warranted to aim for effective treatment and decent quality of life for the majority of long-term surviving pediatric tumor patients.

Retrospective evaluation of the orthodontic treatment needs in primary school children with Robin sequence following Tübingen palatal plate therapy in infancy.

INTRODUCTION: The aim of this study was to investigate the orthodontic treatment needs (OTN) of children with RS treated with the TPP in infancy compared to age- and sex-matched controls. METHODS: The aim of this study was to investigate the orthodontic treatment needs (OTN) of children with RS treated with the TPP in infancy compared to age- and sex-matched controls. RESULTS: In 21 children with RS (n = 23; 19 non-syndromic, 4 syndromic; average age 9.9 years) showed high OTN, which was significantly higher than in controls (n = 21). The latter of 9 controls had minor OTN, followed by 8 participants with borderline OTN. Regarding the intraoral picture, patients with RS had an increased open bite tendency. Without considering the presence of a cleft palate, 16 children with RS had high or very high OTN, compared to 4 of controls. CONCLUSIONS: Patients with RS have significantly higher OTN than healthy controls, independent of cleft occurrence. RS is associated with dental anomalies and special skeletal growth patterns, both increasing malocclusion and negatively affecting dentoalveolar growth. This should raise awareness for identifying these needs and provide a comprehensive orthodontic treatment, where functional rehabilitation should be favored over aesthetic results.

Increased Demand for Pharmaceutical Drugs Containing Potassium Iodide In Connection with the Russia-Ukraine Conflict.

The current conflict between Russia and Ukraine increased concerns in the German population of a release of radioactive substances, e.g.radioactive iodine. A high dose of potassium iodide (PI) may prevent accumulation of radioactive iodine in the thyroid gland. Therefore, the German government keeps a sufficient quantity of PI in stock for public supply in case of an emergency. We investigated ambulatory drug dispensing rates of PI and found that the total dispensing of PI (statutory health insurance (SHI), private health insurance (PHI), and overthe-counter (OTC)) increased by 106% from February to March 2022. Changes in PI dispensing were mainly due to an increase in OTC sales, where PI as an antidote showed a sevenfold increase from around 930 packages (February 2022) to 6,500 packages (March 2022), while SHI and PHI dispensing remained relatively low. Furthermore, we investigated whether these changes in dispensing raised the number of suspected adverse drug reactions (ADR). We found no increase of ADR reports related to the use of PI-containing medicinal products between February and September 2022, neither in our national pharmacovigilance nor in the European EudraVigilance database. The data suggest that the mere possibility of a nuclear disaster in Ukraine raised the demand of PI in Germany. Thus, timely and proactive information and reassurance of the public of supply reliability by the Government in a case of a nuclear emergency could be helpful in preventing potential drug shortages and unfounded concern.

Retrospective single-center historical comparative study between proGAV and proGAV2.0 for surgical revision and implant duration.

OBJECTIVE: Cerebrospinal fluid (CSF) diversion shunt systems remain to be the most common treatment for pediatric hydrocephalus. Different valve systems are used to regulate CSF diversion. Preventing complications such as occlusions, ruptures, malpositioning, and over- or underdrainage are the focus for further developments. The proGAV and proGAV2.0 valve system are compared in this retrospective study for revision-free survival and isolated valve revision paradigms. METHODS: In the first part of the study, the shunt and valve revision-free survival rates were investigated in a retrospective historical comparison design for a period of 2 years in which each valve was used as standard valve (proGAV: July 2012-June 2014; proGAV2.0: January 2015-December 2016) with subsequent 30-month follow-up period, respectively. In the second part of the study, the implant duration was calculated by detecting isolated valve (valve-only) revisions together with another valve explantation during the entire period of the first study and its follow-up period. RESULTS: Two hundred sixty-two patients (145 male and 117 female, mean age 6.2 ± 6.1 years) were included in the cohort of revision-free survival. During the 30-month follow-up period, 41 shunt revisions, including 27 valve revisions (shunt survival rate: 72.1%, valve survival rate: 81.6%) were performed in the proGAV cohort and 37 shunt revisions, including 21 valve revisions (shunt survival rate: 74.8% and valve survival rate: 85.0%) were performed in the proGAV2.0 cohort without showing statistically significant differences. In the second part of the study, 38 cases (mean age 4.0 ± 3.9 years) met the inclusion criteria of receiving a valve-only-revision. In those patients, a total of 44 proGAV and 42 proGAV2.0 were implanted and explanted during the entire study time. In those, a significantly longer implant duration was observed for proGAV (mean valve duration 961.9 ± 650.8 days) compared to proGAV2.0 (mean length of implantation period 601.4 ± 487.8 days; p = 0.004). CONCLUSION: The shunt and valve revision-free survival rates were found to be similar among the groups during 30 month follow-up. In patients who received "valve only" revisions and a subsequent explanation, the implant duration was significantly longer in the proGAV. Although the amount of patients with valve-only-revisions are small compared to the entire cohort certain patients seem to be at higher risk for repeated valve revisions.

Amide proton transfer-weighted MRI in the clinical setting - correlation with dynamic susceptibility contrast perfusion in the post-treatment imaging of adult glioma patients at 3T.

INTRODUCTION: We investigated the correlation between amide proton transfer-weighted magnetic resonance imaging (APTw MRI) and dynamic susceptibility contrast (DSC) perfusion in order to assess the potential of APTw MRI as an alternative to DSC in adult brain tumor (glioma) imaging. METHODS: After Ethical Committee approval, forty adult patients, treated for histopathologically confirmed glioma (World Health Organization (WHO) grade II-IV), were prospectively imaged at 3 Tesla (3 T) with DSC perfusion and a commercially available three-dimensional (3D) APTw sequence. Two consultant neuroradiologists independently performed region of interest (ROI) measurements on relative cerebral blood volume (rCBV) and APTw maps, co-registered with anatomical images. The correlation APTw MRI-DSC perfusion was assessed using Spearman's rank-order test. Inter-observer agreement was evaluated by the intraclass correlation coefficient (ICC) and Bland-Altman (BA) plots. RESULTS: A statistically significant moderately strong positive correlation was observed between maximum rCBV (rCBVmax) and maximum APTw (APTwmax) values (observer 1: r = 0.73; p < 0.01; observer 2: r = 0.62; p < 0.01). We found good inter-observer agreement for APTwmax (ICC = 0.82; 95% confidence interval (CI) 0.66-0.90), with somewhat broad outer 95% CI for the BA Limits of Agreement (LoA) (-1.6 to 1.9). ICC for APTwmax was higher than ICC for rCBVmax (ICC = 0.74; 95%; CI 0.50-0.86), but the difference was not statistically significant. CONCLUSION: APTwmax values correlate positively with rCBVmax in patients treated for brain glioma. APTw imaging is a reproducible technique, with some observer dependence. Results need to be confirmed by a larger population analysis. IMPLICATIONS FOR PRACTICE: APTw MRI can be a useful addition to glioma follow-up imaging and a potential alternative to DSC perfusion, especially in patients where contrast agent is contraindicated.

Biparietal meander expansion technique for sagittal suture synostosis in patients older than 1 year of age-technical note.

OBJECTIVE: Sagittal suture synostosis (SSS) is the most common form of craniosynostosis. For older patients, the strategy for surgical correction needs to consider diminished growth dynamics of the skull and an active reconstruction cranioplasty aims to sustain stability for the active child. We describe our technique of biparietal meander expansion (BME) technique for SSS for patients older than 1 year and retrospectively reviewed the perioperative course as well as the subjective experience of patients and caregivers during follow-up. METHODS: The BME technique incorporates bilateral serpentine craniotomies and fixation of the consecutively expanded bone tongues with crossing sutures for patients with SSS older than 12 months of age at surgery. We reviewed patients undergoing this surgical technique for correction of SSS and collected data about the clinical course and performed a patients reported outcome measure (PROM) for patients or caregivers to evaluate subjective experience and outcome after surgical treatment. RESULTS: BME was performed in 31 patients (8 females; median age: 43 months; range 13-388). The mean length of operation was 172.7±43 minutes (range 115-294). Patients experienced no immediate complications or neurological morbidity after surgery. Considering a total of 21 completed PROM questionnaires, the head shape after surgery was evaluated as either "better" (57%) or "much better" (43%) compared to preoperatively. Eighty-one percent of patients or caregivers answered that the patient experiences no limitation in daily activities. Although 42.8% perceived the hospital as strenuous, 90.5% would choose to undergo this treatment again. CONCLUSION: BME is a feasible technique for older SSS patients resulting in immediate stability of the remodelled calvarium with a more normal head shape. The survey among caregivers or patients revealed a favourable subjectively experienced outcome after this type of surgical treatment of SSS in the more complex context of an older patient cohort.

[Regional distribution of the cochlear implant (CI) centers in Germany]. / Regionale Verteilung der Cochlea-Implantat (CI)-versorgenden Einrichtungen in Deutschland.

The treatment of patients with severe hearing loss or deafness with a cochlear implant (CI) represents a standard in Germany today. However, there is hardly any data on the current number of clinical CI centers (CI clinics) and their geographical distribution. The patient self-help organization, German Cochlear Implant Society (DCIG), and the German Society for Otorhinolaryngology, Head and Neck Surgery (DGHNO-KHC) have therefore initiated a survey to determine the regional distribution, the range of services, the consideration of existing quality standards and cooperation with patient self-help organizations of the individual clinical CI centers.For this purpose, a total number of 170 ENT departments or their directors (37 professors and 133 chief physicians), respectively, were contacted by e-mail and provided with a questionnaire. The survey took place from October 2019 to February 2020.Of the 170 departments contacted, 71 (41.8 %) took part in the survey. Of these, 70 departments (98.6 %) confirmed to perform CI surgeries. Thus, 41.8 % of all clinics contacted reported to perform CI surgeries (70 of 170 clinics), while this information was not available from 99 clinics. All 70 clinical CI centers (100 %) reported to conduct CI surgeries on adults, 60 centers (85.7 %) also on children (< 18 years). 36 departments (51.4 %) reported that the total number of CI surgeries at their facility in 2018 was more than 50. In 64 departments (91.4 %), the recommendations of the DGHNO-KHC on CI care (according to the White Paper CI care 2018) were followed. A collaboration between the department and patient self-help organization was confirmed by 67 institutions (95.7 %). The geographical distribution of the clinical CI centers showed a heterogeneous distribution pattern between the individual federal states and also within the respective federal state.The work presented here is a first assessment of the situation with regard to the regional distribution of clinical CI centers in Germany. A clustering of CI centers was noticeable in metropolitan areas, sometimes with several facilities in one city. The predominant attention to quality-related aspects, such as the consideration of the DGHNO-KHC white paper and the cooperation with patient self-help, is gratifying. The limitations of the study result from limited participation in the survey (41.8 % of the contacted clinics).

Beyond Toxin Transport: Novel Role of ABC Transporter for Enzymatic Machinery of Cereulide NRPS Assembly Line.

Nonribosomal peptide synthetases (NRPSs) and polyketide synthetases (PKSs) play a pivotal role in the production of bioactive natural products, such as antibiotics and cytotoxins. Despite biomedical and pharmaceutical importance, the molecular mechanisms and architectures of these multimodular enzyme complexes are not fully understood. Here, we report on an ABC transporter that forms a vital part of the nonribosomal peptide biosynthetic machinery. Emetic Bacillus cereus produces the highly potent, mitochondrial active nonribosomal depsipeptide cereulide, synthesized by the NRPS Ces. The ces gene locus includes, next to the structural cesAB genes, a putative ABC transporter, designated cesCD Our study demonstrates that tethering of CesAB synthetase to the cell membrane by CesCD is critical for peptide assembly. In vivo studies revealed that CesAB colocalizes with CesCD on the cell membrane, suggesting direct involvement of this ABC transporter in the biosynthesis of a nonribosomal peptide. Mutation of cesCD, disrupting the assembly of the CesCD complex, resulted in decreased interaction with CesAB and, as a consequence, negatively affected cereulide biosynthesis. Specific domains within CesAB synthetase interacting with CesC were identified. Furthermore, we demonstrated that the structurally similar BerAB transporter from Bacillus thuringiensis complements CesCD function in cereulide biosynthesis, suggesting that the direct involvement of ABC transporter in secondary metabolite biosynthesis could be a widespread mechanism. In summary, our study revealed a novel, noncanonical function for ABC transporter, which is essential for megaenzyme functionality of NRPS. The new insights into natural product biosynthesis gained may facilitate the discovery of new metabolites with bioactive potential.IMPORTANCE This study revealed a novel, potentially conserved mechanism involved in the biosynthesis of microbial natural products, exemplified by the mitochondrial active depsipeptide cereulide. Similar to other bioactive substances, such as the last-resort antibiotics vancomycin and daptomycin, the antitumor drug cryptophycin or the cholesterol-lowering agent lovastatin, cereulide is synthesized nonribosomally by multienzyme machinery, requiring the concerted actions of multiple proteins to ensure correct product assembly. Given the importance of microbial secondary metabolites in human and veterinary medicine, it is critical to understand how these processes are orchestrated within the host cells. By revealing that tethering of a biosynthetic enzyme to the cell membrane by an ABC transporter is essential for nonribosomal peptide production, our study provides novel insights into synthesis of microbial secondary metabolites, which could contribute to isolation of novel compounds from cryptic secondary metabolite clusters or improve the yield of produced pharmaceuticals.

Endoscopic third ventriculostomy in children with third ventricular pressure gradient and open ventricular outlets on MRI.

OBJECTIVE: Patients with non-communicating hydrocephalus due to aqueductal stenosis are often successfully treated with endoscopic third ventriculocisternostomy (ETV). In hydrocephalus, due to other locations of obstruction of the major CSF pathways, endoscopic treatment may also be a good option. We investigated our cohort of patients treated by ETV with patent ventricular outflow but pressure gradient signs at the third ventricle in a single-center retrospective study. METHODS: We retrospectively reviewed records and imaging studies of 137 patients who underwent an ETV in our department in the time period of June 2010 to March 2018. We included patients who showed the following findings in MRI: 1st: open Sylvian aqueduct, 2nd: open outlets of the 4th ventricle, 3rd: open spinal canal, 4th: intra-/extraventricular pressure gradient seen at the 3rd ventricle and excluded patients with history of CSF infection or hemorrhage. Perioperative clinical state and possible complications or reoperations were recorded. Shunt dependency and changes in ventricular dilatation were measured as frontal and occipital horn ratio (FOHR) before surgery and during follow-up. RESULTS: A total of 21 patients met the defined criteria. During the mean follow-up time of 40.7 ± 30 months (range; 5-102 months), two children had to undergo a re-ETV, and six children (all < 1 year of age) received a VP shunt. ETV shunt-free survival was 100% for children > 1 year of age. The ventricular width measured as FOHR was significantly reduced after ETV 0.5 ± 0.08 (range 0.42-0.69; p < 0.05). FOHR was significantly reduced at last follow-up shunt independent patients (0.47 ± 0.05; range 0.41-0.55; p < 0.001) CONCLUSION: We conclude that ETV seems to be a successful treatment option for patients with MRI signs of intra-/extraventricular pressure gradient at the 3rd ventricle and patent aqueduct and fourth ventricular outlets in children older than 1 year of age. This condition is observed only rarely and warrants further research on a multicenter basis in order to get more solid data of its pathophysiology.

Influence of Extracellular Acidosis on Matrix Protein Homeostasis in Tumour Cells and Fibroblasts.

Pathogenesis of tumour development comprises among others changes of its microenvironment that can be caused by tumour cells or stroma cells like fibroblasts and include extracellular acidosis. Acidosis then may have impact on tumour cells, fibroblasts and their cross-talk, leading for example to an altered matrix protein homeostasis. The mentioned changes can support tumour progression. In the present study the influence of metabolic acidosis on matrix proteins in tumour cells, fibroblasts and their co-culture was evaluated. The experiments were performed in rat tumour cells (AT-1), normal rat kidney fibroblasts (NRKF) and their co-culture. Cells were exposed to acidic media for up to 48 h. Changes of collagen I and fibronectin were measured: mRNA content by RT-PCR, intracellular protein by immune blot and extracellular proteins by direct ELISA. In AT-1 cells acidosis led to decreased secretion of collagen I and fibronectin. The mRNA of both was unchanged and intracellular collagen I was decreased. In NRKF extracellular collagen I was increased and fibronectin unchanged. The collagen I and fibronectin mRNA was unchanged and intracellular collagen I was increased. In the co-culture media, collagen I changes vanished and fibronectin was decreased. In co-culture the mRNA content of collagen I and fibronectin in AT-1 was unchanged but both were increased in NRKF. In AT-1 and NRKF mono-culture extracellular matrix protein changes seem to be the result of posttranscriptional regulation.

Attachment and adaptation to breast cancer: The mediating role of avoidant emotion processes.

Attachment insecurity is associated with difficulties in adapting to cancer. Accumulating evidence points to the influence of avoidant emotion processes in this association. This study explored this pathway by examining the association between attachment insecurity and quality of life in women with breast cancer, and by exploring the mediating role of two avoidant emotion processes in this association. Women with breast cancer (N = 155) completed measures of attachment, emotional suppression, emotional awareness and quality of life. Avoidance of attachment was positively associated with emotional suppression (ß = .29, p < .01) and lack of emotional awareness (ß = .27, p < .01), and negatively associated with quality of life (ß = -.22, p < .05). Lack of emotional awareness partially mediated the relationship between attachment avoidance and quality of life (indirect effect ß = -.12, p = .008). Attachment anxiety was not associated with any variable. Attachment avoidance may hinder the process of adaptation to breast cancer and difficulties in identifying and describing emotions may be partly responsible for this influence. Access to and ability to benefit from social and medical supports is likely to depend on being able to engage with others and recognise and process emotions effectively. Research and clinical implications are discussed.

Factors associated with prescribing costs: analysis of a nationwide administrative database.

OBJECTIVE: All health care systems in the world struggle with rising costs for drugs. We sought to explore factors impacting on prescribing costs in a nationwide database of ambulatory care in Germany. Factors identified by this research can be used for adjustment in future profiling efforts. METHODS: We analysed nationwide prescription data of physicians having contractual relationships with statutory health insurance funds in 2014. Predictor and outcome variables were aggregated at the practice level. We performed analyses separately for primary care and specialties of cardiology, gastroenterology, neurology and psychiatry, pulmology as well as oncology and haematology. Bivariate robust regressions and Spearman rank correlations were computed in order to find meaningful predictors for our outcome variable prescription costs per patient. RESULTS: Median age of patients and proportion of DDD issued were substantial predictors for prescription costs per patient in Primary Care, Cardiology, and Pulmology with explained variances between 41 and 61%. In Neurology and Psychiatry only proportion of patients with polypharmacy ≥ 2 quarters was a significant predictor for prescription costs per patient, explaining 20% of the variance. For gastroenterologists, oncologists and haematologists no stable models could be established. CONCLUSIONS: Any analysis of prescribing behaviour must take the degree into account to which an individual physician or practice is responsible for prescribing patients' medication. Proportion of prescriptions/DDDs is an essential confounder for future studies of drug prescribing.

The use of a smartphone-assisted ventricle catheter guide for Ommaya reservoir placement-experience of a retrospective bi-center study.

BACKGROUND: For intraventricular chemotherapy (IVC) as part of many oncological treatment protocols, Ommaya reservoir is enabling repeated access to the cerebro-spinal fluid (CSF). The correct placement of the catheter in the ventricle is essential for correct application of drugs, which is enabled by sophisticated techniques such as neuronavigation. OBJECTIVE: In a bi-center retrospective study, we reviewed our experience using a smartphone-assisted ventricle catheter guide as simple solution for correct Ommaya reservoir placement. METHODS: Sixty Ommaya reservoirs have been placed in 60 patients between 2011 and 2017 with the smartphone-assisted ventricular catheter guidance technique. Patient characteristics, preoperative frontal and occipital horn ratio (FOHR), postoperative catheter position, and complications were assessed. RESULTS: The majority of our patients (71.6%) have got narrow or slit-like ventricles (FOHR ≤ 0.4). All Ommaya reservoirs were placed successfully. Fifty-eight ventricular catheters (97%) were inserted at the first and 2 (3%) at the second attempt using the same technique. No immediate perioperative complications were observed. All catheters (100%) could be used for IVC. Postoperative imaging was available in 52 patients. Thirty-two (61.5%) of ventricular catheters were rated as grade I, 20 (38.5%) as grade II, and none (0%) as grade III. Four patients (6.7%) showed postoperative complications during a median follow-up of 8.5 months (hydrocephalus, n = 1; infection, n = 1; parenchymal cyst around catheter, n = 1; shunt revision, n = 1). CONCLUSIONS: The smartphone-assisted guide offers decent accuracy of ventricle catheter placement with ease and simplicity for a small surgical intervention. We propose this technique as routine tool for Ommaya reservoir placement independent of lateral ventricular size to decrease the rate of ventricle catheter malposition as reasonable alternative to a neuronavigation system.

Different inflammatory responses of bovine oviductal epithelial cells in vitro to bacterial species with distinct pathogenicity characteristics and passage number.

The bovine oviduct provides the site for fertilization and early embryonic development. Modifications to this physiological environment, for instance the presence of pathogenic bacterial species, could diminish reproductive success at early stages of pregnancy. The aim of this study was to elucidate the inflammatory responses of bovine oviductal epithelial cells (BOEC) to a pathogenic bacterial species (Trueperella pyogenes) and a potentially pathogenic bacterium (Bacillus pumilus). BOEC from four healthy animals were isolated, cultured in passage 0 (P0) and passaged until P3. Trypan blue staining determined BOEC viability during 24 h co-culture with different multiplicities of infection (MOI) of T. pyogenes (MOI 0.01, 0.05, 0.1 and 1) or B. pumilus (MOI 1 and 10). BOEC remained viable when co-cultured with T. pyogenes at MOI 0.01 and with B. pumilus at MOI 1 and 10. Extracted total RNA from control and bacteria co-cultured samples was subjected to reverse transcription-quantitative polymerase chain reaction (RTq-PCR) to determine mRNA expression of various studied genes. The rate of release of interleukin 8 (IL8) and prostaglandin E2 (PGE2) from BOEC was measured by ELISA after 24 h co-culture with bacteria. RT-qPCR of various selected pro-inflammatory factors revealed similar mRNA expression of pro-inflammatory factors in BOEC co-cultured with T. pyogenes and in the controls. Higher mRNA expression of IL 1A, -1B, tumor necrosis factor alpha and CXC ligand (CXCL) 1/2, -3, -5 and IL8 and PG synthesis enzymes in BOEC co-cultured with B. pumilus was observed. In the presence of B. pumilus a higher amount of IL8 and PGE2 was released from BOEC than from controls. The viability and pro-inflammatory response of P3 BOEC incubated with bacteria was lower than in P0 BOEC. These findings illustrate the pathogenicity of T. pyogenes towards BOEC in detail and the potential role of B. pumilus in generating inflammation in oviductal cells. Culturing conditions influenced the pro-inflammatory responses of BOEC towards bacteria. Therefore, researchers conducting epithelial-bacterial in vitro co-culture should not underestimate the effects of these parameters.

Asociación del déficit de vitamina D con patologías de la piel humana / Association of vitamin D deficiency with human skin pathologies

La vitamina D es una de las vitaminas fundamentales en el día a día del ser humano. No solo juega un rol importante en la homeostasis del calcio y salud ósea, sino también en distintos sistemas del organismo. El déficit de esta vitamina se ha asociado a enfermedades como: cánceres, hipertensión y síndrome metabólico. La epidermis es la principal fuente de vitamina D del organismo, seguida de una dieta rica en vegetales, pescados y leche fortificada. Esta capa de la piel no sólo es productora, sino además presenta diversas patologías producto del déficit de este nutriente. La vitamina D regula la función de la barrera cutánea, a través de la modulación de la expresión de filagrina e involucrina. La filagrina es una proteína estructural de la piel, que produce agregación y compactación de los filamentos intermedios de queratina. Esta proteína estaría implicada en el desarrollo de la dermatitis atópica. La vitamina D promueve la diferenciación celular e inhibe la proliferación y reduce el crecimiento de tumores, tal como ocurre en el melanoma maligno, a través de la expresión de su receptor (VDR). Dado los actuales descubrimientos respecto del déficit de este nutriente, la recomendación actual es consumir productos lácteos de forma habitual, asociado a la exposición de 5 minutos diarios idealmente en horarios de menor irradiación UV, manteniendo el uso de bloqueador solar y ropa adecuada durante el día. En conclusión, la vitamina D no sólo presenta utilidad en la mantención del equilibrio óseo, sino que interactúa a través de su receptor en diversos tejidos del organismo, permitiendo la homeostasis de la piel.

Vitamin D is one of the essential vitamins in the evolutionary development on earth. The best known of this function is the regulation of calcium homeostasis. Deficiency of this vitamin has been associated with some cancers, hypertension and metabolic syndrome. The epidermis is the main source of vitamin D in the body, followed by a diet increased vegetables, fish and fortified milk. The epidermis is not productive but also presents several pathologies resulting from the deficiency of this nutrient. The VD regulates the function of the cutaneous barrier through the modulation of filagrine and involucrin expression. Filagrine is a structural protein in the skin that produces aggregation and compaction of intermediate keratin filaments. This protein would be involved in the development of atopic dermatitis. Vitamin D promotes cell differentiation and inhibits proliferation and reduces the growth of tumors, as in malignant melanoma, through receptor expression (VDR). Given the current findings regarding the deficiency of this nutrient, the current recommendation is to consume dairy products in a habitual way, associated to the exposure of only 5 minutes daily ideally at times of lower UV irradiation, maintaining the use of sunscreen and proper clothing during the day. In conclusion, vitamin D, not only has utility in maintaining the bone balance, but interacts through its receptor in various tissues of the body, allowing the homeostasis of the skin, vascular tissue among others.

Augmented reality in intraventricular neuroendoscopy.

BACKGROUND: Individual planning of the entry point and the use of navigation has become more relevant in intraventricular neuroendoscopy. Navigated neuroendoscopic solutions are continuously improving. OBJECTIVE: We describe experimentally measured accuracy and our first experience with augmented reality-enhanced navigated neuroendoscopy for intraventricular pathologies. PATIENTS AND METHODS: Augmented reality-enhanced navigated endoscopy was tested for accuracy in an experimental setting. Therefore, a 3D-printed head model with a right parietal lesion was scanned with a thin-sliced computer tomography. Segmentation of the tumor lesion was performed using Scopis NovaPlan navigation software. An optical reference matrix is used to register the neuroendoscope's geometry and its field of view. The pre-planned ROI and trajectory are superimposed in the endoscopic image. The accuracy of the superimposed contour fitting on endoscopically visualized lesion was acquired by measuring the deviation of both midpoints to one another. The technique was subsequently used in 29 cases with CSF circulation pathologies. Navigation planning included defining the entry points, regions of interests and trajectories, superimposed as augmented reality on the endoscopic video screen during intervention. Patients were evaluated for postoperative imaging, reoperations, and possible complications. RESULTS: The experimental setup revealed a deviation of the ROI's midpoint from the real target by 1.2 ± 0.4 mm. The clinical study included 18 cyst fenestrations, ten biopsies, seven endoscopic third ventriculostomies, six stent placements, and two shunt implantations, being eventually combined in some patients. In cases of cyst fenestrations postoperatively, the cyst volume was significantly reduced in all patients by mean of 47%. In biopsies, the diagnostic yield was 100%. Reoperations during a follow-up period of 11.4 ± 10.2 months were necessary in two cases. Complications included one postoperative hygroma and one insufficient fenestration. CONCLUSIONS: Augmented reality-navigated neuroendoscopy is accurate and feasible to use in clinical application. By integrating relevant planning information directly into the endoscope's field of view, safety and efficacy for intraventricular neuroendoscopic surgery may be improved.

Valve exchange towards an adjustable differential pressure valve with gravitational unit, clinical outcome of a single-center study.

OBJECTIVE: Overdrainage in children is a long-term problem for shunted patients which might lead to chronic anatomical changes. In order to prevent these problems, valve exchange is performed on a regular basis in patients without hydrostatic units towards a valve with both an adjustable and a gravitational unit. The clinical outcome of these patients is reported in a retrospective study. METHODS: Between 2009 and 2014, the in-house database was analyzed for patients who received a valve exchange towards an adjustable differential pressure valve with gravitational unit. The study protocol included the patients shunt history, image analysis for ventricular width, and necessity of revision surgery after valve exchange. A questionnaire was sent to the patients in order to ask for their subjective experience for symptom changes and treatment experience. RESULTS: Forty-six patients were identified (26 girls, mean age 11.8 ± 6.1 years) with a mean follow-up of 36.3 ± 15 months. The ventricular width did increase after valve exchange as measured in frontal and occipital horn ratio (0.364 ± 0.032 vs. 0.402 ± 0.09, p = 0.0017). Of the patients suffering from acute symptoms, 89% improved after treatment. The shunt and valve survival rates were 88 and 95%, respectively, after 12 months. Comparing the total amount of revisions before and after valve exchange, a significant reduction was seen in total but a no significant difference was analyzed in amount of revisions to time ratio. CONCLUSION: Valve exchange might be cautiously decided if patients seem to perform clinically well. In our study, we were able to show that the strategy of valve exchange to prevent chronic overdrainage is well tolerated and seem to improve patient's clinical outcome in terms of ventricular width, symptom relieve, and revision rate.

[Reconstruction of the medial patellofemoral ligament after lower-leg amputation]. / MPFL-Plastik nach Unterschenkelamputation.

The reconstruction of the medial patellofemoral ligament has been an increasingly popular approach for patellar instability over the last ten years. It is a conglomeration of symptoms with varying degree of severity. For pinpointed surgery planning, magnetic resonance imaging is now the obligate diagnosic tool. Therefore, in the preoperative stage, collateral pathology can be observed.

Do patients with diabetes type 2 or chronic heart failure understand a medication plan?

A standardized medication plan (MP) was recently enacted into German law (§ 31a SGB V). The purpose of our study was to assess if patients with chronic diseases requiring polymedication understand the standardized MP and can transfer the given information into practice. 100 patients who took at least five medicines regularly were prospectively included in a cross-sectional study: 50 patients with the primary diagnosis chronic heart failure (CHF), and 50 with diabetes mellitus type 2 (DMT2). We performed a structured test-scenario studying the handling of a provided MP then evaluated the execution of the information on the MP by filling pill boxes and requested patients' opinion. An established weighted scoring system, the "Evaluation Tool to test the handling of the Medication Plan" (ET-MP) was applied to quantitate the ability of the patients to handle the MP. In addition, signs of depression, cognitive function and self-care behavior in chronic heart failure were characterized using the PHQ-9, Mini-Cog, and G9-EHFScB-9 questionnaires, respectively. The understanding of the MP was poor and irrespective of the underlying primary diagnosis. Only 32% of all patients were able to handle the MP without difficulties (ET-MP score >90%), the median ET-MP score was 83 [(IQR) 50-98]. Comprehension of the MP was better in patients aged <70 years compared to ≥70 years (p<0.01). Patients ≥10 years of education achieved higher ET-MP results than patients with <10 years of education (p<0.01). Patients with signs of cognitive impairment exhibited significantly lower ET-MP scores than patients without cognitive impairment (p<0.001). There were no significant correlations of the ET-MP score with number of daily medications, living situation, sex, the Charlson Comorbidity Index, the PHQ-9 score, and use of a dosing aid or possession of a medication list.