INSPIRA: study protocol for a randomized-controlled trial about the effect of spirometry-assisted preoperative inspiratory muscle training on postoperative complications in abdominal surgery.

BACKGROUND: Rehabilitation strategies after abdominal surgery enhance recovery and improve outcome. A cornerstone of rehabilitation is respiratory physiotherapy with inspiratory muscle training to enhance pulmonary function. Pre-habilitation is the process of enhancing functional capacity before surgery in order to compensate for the stress of surgery and postoperative recovery. There is growing interest in deploying pre-habilitation interventions prior to surgery. The aim of this study is to assess the impact of preoperative inspiratory muscle training on postoperative overall morbidity. The question is, whether inspiratory muscle training prior to elective abdominal surgery reduces the number of postoperative complications and their severity grade. METHODS: We describe a prospective randomized-controlled single-centre trial in a tertiary referral centre. The primary outcome is the Comprehensive Complication Index (CCI) at 90 days after surgery. The CCI expresses morbidity on a continuous numeric scale from 0 (no complication) to 100 (death) by weighing all postoperative complications according to the Clavien-Dindo classification for their respective severity. In the intervention group, patients will be instructed by physiotherapists to perform inspiratory muscle training containing of 30 breaths twice a day for at least 2 weeks before surgery using Power®Breathe KHP2. Depending on the surgical schedule, training can be extended up to 6 weeks. In the control group, no preoperative inspiratory muscle training will be performed. After the operation, both groups receive the same physiotherapeutic support. DISCUSSION: Existing data about preoperative inspiratory muscle training on postoperative complications are ambiguous and study protocols are often lacking a clear design and a clearly defined endpoint. Most studies consist of multi-stage concepts, comprehensively supervised and long-term interventions, whose implementation in clinical practice is hardly possible. There is a clear need for randomized-controlled studies with a simple protocol that can be easily transferred into clinical practice. This study examines the effortless adjustment of the common respiratory physiotherapy from currently postoperative to preoperative. The external measurement by the device eliminates the diary listing of patients' performances and allows the exercise adherence and thus the effect to be objectively recorded. TRIAL REGISTRATION: ClinicalTrials.gov NCT04558151 . Registered on September 15, 2020.

Cross-sectional point prevalence survey to study the environmental contamination of nosocomial pathogens in intensive care units under real-life conditions.

BACKGROUND: In intensive care units (ICUs), inanimate surfaces and equipment may be contaminated by nosocomial pathogens, including multi-drug-resistant micro-organisms. AIMS: To assess the degree of environmental contamination close to and distant from patients, and contamination of healthcare workers' (HCWs) hands with nosocomial pathogens under real-life conditions and to investigate potential transmission events. METHODS: Over the course of three weeks, agar contact samples were taken close to and distant from patient areas and from HCWs' hands in eight ICUs of a tertiary care hospital in Innsbruck, Austria. Each ICU was visited once without announcement. Species identification and antimicrobial susceptibility testing were performed according to standard methods, and corresponding strains from patient, environment and hand samples were genotyped using pulsed-field gel electrophoresis. FINDINGS: Among 523 samples, HCWs' hands were most frequently contaminated with potentially pathogenic bacteria (15.2%), followed by areas close to patients (10.9%) and areas distant from patients (9.1%). Gram-positive bacteria were identified most often (67.8%), with Enterococcus spp. being the most prevalent species (70% vancomycin sensitive and 30% vancomycin resistant) followed by Staphylococcus aureus, of which 64% were classified as meticillin-resistant Staphylococcus aureus. Molecular typing documented identical strains among patient, environment and hand isolates. CONCLUSION: This study found widespread contamination of the ICU environment with clinically relevant pathogens, including multi-drug-resistant micro-organisms, despite cleaning and disinfection. The bioburden might not be restricted to areas close to patients. The role of extended environmental disinfection of areas distant from patients in order to improve infection prevention needs further discussion.

The impact of coagulopathy on the outcome of traumatic epidural hematoma.

PURPOSE: To evaluate the impact of trauma-associated coagulation disorders on the neurological outcome in patients with traumatic epidural hematoma undergoing surgical or non-surgical treatment. A retrospective analysis was performed using prospectively collected data in a consecutive patient series from a level 1 trauma center. METHODS: Eighty-five patients with traumatic epidural hematoma were identified out of 1,633 patients admitted to our emergency room with traumatic head injuries between October 2004 and December 2008. The following prospectively assessed parameters were analyzed: Glasgow Coma Scale, coagulopathy, presence of skull fractures, additional injuries, the Injury Severity Score, hematoma volume and thickness at admission, hematoma volume progression over time and neurologic symptoms. Furthermore, patients were grouped based on whether they had undergone surgical or non-surgical treatment of the epidural hematoma. Clinical outcome was determined according to the Glasgow Outcome Score (GOS) at hospital discharge. RESULTS: Patients with coagulopathy showed significantly lower GOS values compared to patients with intact blood coagulation. Initial and progressive hematoma volumes did not influence neurological outcome. Patients with multiple injuries did not show a worse outcome compared to those with isolated epidural hematoma. There was no difference in patient's outcome after surgical or non-surgical treatment. CONCLUSIONS: Poor outcome after traumatic epidural hematoma was associated with coagulopathy. Progression of epidural hematoma volume was not associated with coagulopathy or with poor neurological outcome. Prospective studies are needed to confirm these results.

Correlation of outcome to neurosurgical lesions: confirmation of a new method using data after microelectrode-guided pallidotomy.

The purpose of this study was the development of a new method to correlate functional surgery with outcome measures. Lesions following microelectrode guided globus pallidus internus (GPi) pallidotomy for Parkinson's disease are presented to demonstrate this new method in regard to clinical outcome. A clinical series of 26 patients with extensive neurological and neuropsychological data were studied. Three-month postoperative MRI lesion borders at the AC-PC plane were scaled to a standard size, and the lesions were stored in a virtual array with a cell size of one voxel. The average outcome measure for each voxel is presented graphically. Unified Parkinson's disease rating scale (UPDRS) motor scores improved more with posterolateral and centrally located GPi lesions than with anteromedial lesions. A correlation of lesion location to outcome was also visible for subscales of the UPDRS. The distributions were similar for the left and right sides, as well as for ipsi- and contralateral measurements. In general, verbal fluency decreased after lesioning the dominant hemisphere, and posterolateral lesions caused less impairment. This method enables associative analyses between brain area and outcome down to the size of a few voxels. This may be particularly helpful for planning and validating neurosurgical targets for various disorders.

Bilateral thalamic deep brain stimulation: midline tremor control.

OBJECTIVES: To determine the efficacy of bilateral deep brain stimulation (DBS) for management of midline tremor (head, voice, tongue, trunk) in patients with essential tremor. DESIGN: Prospective assessment of tremor at baseline (presurgical), and postoperatively at 1, 3, and 12 months, and annually thereafter. METHODS: A clinical series of 22 individuals undergoing staged, bilateral DBS for treatment of essential tremor. The tremor rating scale was the primary outcome measure. RESULTS: Midline tremor showed significant improvement with stimulation "on" at nearly every postoperative interval when compared with stimulation "off" and with baseline tremor. Bilateral stimulation was associated with a significant incremental improvement in midline tremor control compared with unilateral stimulation: average "stimulation on" percentage change in midline tremor from the unilateral to bilateral period was 81%. Head and voice tremor showed the most consistent improvement. Among those requiring a change in stimulation parameters because of side effects, dysarthria, disequilibrium, motor disturbances, and paraesthesiae were the most common. Dysarthria was more common with bilateral (n = 6; 27%) than with unilateral (n = 0) stimulation. Stimulation parameters remained largely unchanged after the first three months. Nine of 44 leads placed (20%) required subsequent repositioning or replacement. CONCLUSIONS: Unilateral thalamic stimulation significantly improves midline tremor, and subsequent bilateral thalamic stimulation offers an additional incremental improvement in midline tremor control.

Thalamic deep brain stimulation for essential tremor: recommendations for long-term outcome analysis.

OBJECTIVES: Determine the efficacy of thalamic deep brain stimulation (DBS) for tremor control among individuals with essential tremor (ET). METHODS: A clinical series of 52 consecutive individuals undergoing placement of a DBS system for treatment of ET completed an unblinded battery of subjective and objective measures at postoperative intervals of one, three, and 12 months, and annually thereafter up to three years. The assessment battery included measures of tremor and activities of daily living. RESULTS: Both subjective and objective measures showed that stimulation was associated with significant improvement at nearly every postoperative interval as compared to pre-operative and stimulation 'off' ratings of activities of daily living functioning, midline tremor, contralateral upper extremity tremor, and contralateral lower extremity tremor. Ipsilateral tremor showed some improvement with stimulation, but only within the first three months. Trend analysis showed stable tremor control. Stimulation settings remained largely unchanged after the first three months. Dysarthria was more common among those with bilateral stimulation. A range of missing data estimation methods were performed, and subsequent analyses corroborated the main findings of the study. CONCLUSION: Thalamic DBS is generally a well-tolerated and effective treatment for ET. Methodological and analytical recommendations are provided for the evaluation of long-term outcome.

Quantitative and qualitative outcome measures after thalamic deep brain stimulation to treat disabling tremors.

OBJECTIVE: We studied outcome measures after unilateral and bilateral thalamic stimulation to treat disabling tremor resulting from essential tremor and Parkinson's disease. The surgical technique, qualitative and quantitative tremor assessments, stimulation parameters, locations of active electrodes, complications, and side effects are described and analyzed. METHODS: Forty-one patients with essential tremor or Parkinson's disease underwent implantation of 56 thalamic stimulators. Preoperative qualitative and quantitative tremor measurements were compared with those obtained after unilateral and bilateral surgery, with activated and deactivated stimulators. Stimulation parameters and stimulation-related side effects were recorded, and outcome measures were statistically analyzed. RESULTS: Qualitative measurements demonstrated significant improvement of contralateral upper-limb (P < 0.001), lower-limb (P < 0.01), and midline (P < 0.001) tremors after unilateral surgery. Ipsilateral arm tremor also improved (P < 0.01). No differences were observed with the Purdue pegboard task. Quantitative accelerometer measurements were correlated with qualitative assessments and confirmed improvements in contralateral resting (P < 0.001) and postural (P < 0.01) tremors and ipsilateral postural tremor (P < 0.05). Activities of daily living improved after unilateral surgery (P < 0.001) and additionally after bilateral surgery (P < 0.05). Adjustments of the pulse generator were required more frequently for tremor control than for amelioration of side effects. Bilateral thalamic stimulation caused more dysarthria and dysequilibrium than did unilateral stimulation. Stimulation-related side effects were reversible for all patients. Stimulation parameters did not change significantly with time. A significantly lower voltage and greater pulse width were used for patients with bilateral implants. CONCLUSION: Unilateral thalamic stimulation and bilateral thalamic stimulation are safe and effective procedures that produce qualitative and quantitative improvements in resting, postural, and kinetic tremor. Thalamic stimulation-related side effects are mild and reversible.

Simultaneous thalamic deep brain stimulation and implantable cardioverter-defibrillator.

Thalamic deep brain stimulation is becoming increasingly popular for the control of drug-refractory tremor. Implantable cardiac pacemakers and defibrillators are commonly used therapeutic modalities. Concerns exist about the potential interactions between these 2 devices in the same patient, but no experience has been reported previously. We describe a patient with essential tremor who had a deep brain stimulator implanted into the left ventral intermediate nucleus of thalamus, who subsequently needed an implantable cardioverter-defibrillator. Despite concerns about possible interactions between the 2 types of implanted electrical devices (i.e., a situation similar to drug-drug interactions), the deep brain stimulator and the implanted pacemaker-defibrillator functioned appropriately, and no interaction occurred in our patient.

Predictors of neuropsychological outcome in patients following microelectrode-guided pallidotomy for Parkinson's disease.

OBJECT: The authors studied neuropsychological performance following microelectrode-guided posteroventral pallidotomy in patients with Parkinson's disease (PD) and evaluated correlations with presurgical and surgical factors. METHODS: Neuropsychological changes 3 months (43 patients) and 12 months (27 patients) after microelectrode-guided pallidotomy for PD are reported in a series of 44 consecutive patients with the disease, who improved neurologically, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) in both the "off' (p<0.001) and best "on" (p<0.001) states. Findings of the vocabulary subtest of the Wechsler Adult Intelligence Scale-Revised (p<0.01), Letter Fluency (p<0.001), Verbal Fluency for semantic categories (p<0.001), and the Wisconsin Card Sorting Test (p<0.01) showed a significant decline in neuropsychological performance in patients 3 months after undergoing left-sided pallidotomy. Impairment in the language domain (semantic fluency) persisted at the 12-month follow-up examination (p<0.01). Visual memory improved after right-sided pallidotomies (p<0.01 after 3 months), with a nonsignificant trend toward persistent improvement 1 year postsurgery (p<0.02 after 12 months). Preoperative semantic fluency was influenced by patient age (p<0.001) and by the width of the third ventricle (p<0.05), as measured by magnetic resonance imaging. A regression model revealed that semantic fluency 3 months postoperatively was significantly affected by the baseline score (p<0.001), side of surgery (p<0.001), handedness (p<0.01), and patient age (p<0.05). However, postoperative lesion volume, lesion location, number of tracks, number of lesions, distance from anatomical landmarks, or UPDRS score did not significantly contribute to neuropsychological outcome. CONCLUSIONS: Neuropsychological changes in a cohort of patients with PD who underwent pallidotomy and experienced excellent clinical benefits and minimum postoperative complications, emphasize the importance of neuropsychological examinations and further investigation of predictive factors.

Computer-assisted neurosurgery by using a noninvasive vacuum-affixed dental cast that acts as a reference base: another step toward a unified approach in the treatment of brain tumors.

OBJECT: The purpose of the study was to evaluate the use of the Vogele-Bale-Hohner (VBH) mouthpiece, which is attached to the patient's upper jaw by negative pressure, for patient-image registration and for tracking the patient's head during image-guided neurosurgery. METHODS: A dynamic reference frame (DRF) is reproducibly mounted on the mouthpiece. Reference points, optimally distributed and attached to the mouthpiece, are used for registration in the patient's absence on the day before surgery. In the operating room, the mouthpiece and DRF are precisely repositioned using a vacuum, and the patient's anatomical structures are automatically registered to corresponding ones on the image. Experimental studies and clinical experiences in 10 patients confirmed repeated (rigid body) localization accuracy in the range of 0 to 2 mm, throughout the entire surgery despite movements by the patient. CONCLUSIONS: Because of its noninvasive, rigid, reliable, and reproducible connection to the patient's head, the VBH vacuum-affixed mouthpiece grants the registration device an accuracy comparable to invasive fiducial markers.

Thalamic stimulation for the treatment of midline tremors in essential tremor patients.

The authors prospectively collected unblinded data from 27 consecutive patients following thalamic stimulation. A significant reduction of midline tremor was achieved after unilateral surgery, but a staged contralateral surgery had an additional effect. A subgroup analysis showed significant beneficial effects for head, voice, tongue, and face tremor. The most frequent reversible side effects were disequilibrium, dysarthria, and paresthesias. We observed more pulse generator adjustments for speech problems in the bilaterally implanted group.

Vascular endothelial growth factor (VEGF) is elevated in brain tumor cysts and correlates with tumor progression.

Vascular endothelial growth factor (VEGF), a key regulatory protein in neoangiogenesis, is strongly expressed in a variety of primary brain tumors, particularly malignant gliomas. In previous studies, high levels of VEGF were also reported in tumor cysts of glioblastomas. Using an ELISA method we measured the concentration of VEGF in matched samples of aspiration fluid from tumor cysts and serum. Samples were collected from 14 patients with primary brain tumors of various histology (six glioblastomas, one protoplasmatic astrocytoma, two pilocytic astrocytomas, one ependymoma, one meningioma, and three craniopharyngiomas) and two patients with solitary cystic brain metastases from adenocarcinomas of the lung. Aspiration fluids of tumor cysts from all patients revealed high VEGF levels ranging between 882 and 1,263,000 pg/ml, which were 2 to more than 2,000 times higher than the corresponding serum levels. Maximum VEGF levels were detectable in cyst fluids from recurrent glioblastoma. Serum VEGF levels ranged between 125 and 716 pg/ml and did not differ from serum levels in 145 healthy volunteers. In a single patient with metastatic lung cancer the concentration of VEGF in serum and cyst fluid was determined during disease progression. During 60 days of follow-up VEGF concentrations in the cyst fluid collected by puncture of an Ommaya reservoir increased 650-fold, while serum levels remained rather constant. These findings indicate that immunoreactive VEGF is produced at the tumor site and abundantly released into the cyst fluid of primary and metastatic brain tumors. Interestingly, this abundant local release is not reflected in serum VEGF levels, even in the case of very high VEGF concentrations in tumor cysts. Thus, VEGF may be biologically relevant for the formation of tumor cysts in brain tumors and correlates with local disease progression.

Uptake and kinetics of 14C-labelled meta-tetrahydroxyphenylchlorin and 5-aminolaevulinic acid in the C6 rat glioma model.

Meta-tetrahydroxyphenylchlorin (m-THPC) and 5-aminolaevulinic acid (5-ALA) are two second-generation photosensitizers which are currently under investigation for photodynamic therapy (PDT) and photodynamic diagnosis (PDD). So far, the experience with these photosensitizers for use within brain tumours is limited. We examined the distribution and retention of 14C-labelled m-THPC and [14C]5-ALA in the rat C6 glioma brain tumour model. After intraperitoneal injection of m-THPC (71,909 d.p.m. microl(-1); 0.16 mg ml(-1) m-THPC; 0.3 mg kg(-1)), the following activities were found after 36 h: brain tumour 223,664 d.p.m. g(-1), brain contralateral to the tumour side 2567 d.p.m. g(-1), liver 369,959 d.p.m. g(-1) and skin 55,197 d.p.m. g(-1); 100,000 d.p.m. corresponding to 0.22 microg of m-THPC. After 7 days, the concentration of m-THPC decreased to 76,277 d.p.m. g(-1) in tumour and 635 d.p.m. g(-1) in brain. The radioactivity after intravenous administration of [14C]5-ALA (23,079 d.p.m. microl(-1); 40 mg ml(-1); 120 mg kg(-1)) increased within 15 min (59,634 d.p.m. g(-1) in tumour, 17,427 d.p.m. g(-1) in brain); after 8 h only a small amount (3653 d.p.m. g(-1) in tumour) remained. Brain adjacent to the tumour was also found to have a higher uptake of 5-ALA. This study provides basic information for the use of m-THPC and 5-ALA in brain tumours. Because of the different pharmacokinetic and toxicological profile, we recommend m-THPC for PDT and 5-ALA for PDD. Clinical trials now have to prove the superior phototoxic properties of these second-generation photosensitizers.

Three-dimensional computer assisted magnetic resonance imaging for neurosurgical planning in parasagittal and parafalcine central region tumors.

Usually, conventional magnetic resonance spin echo images (MRI) are sufficient to establish the diagnosis of intracranial pathology. Planning and executing a neurosurgical procedure requires the ability of the neurosurgeon to transform these two-dimensional MRI into a three-dimensional (3-D) virtual image of the pathology and the surrounding neuronal anatomy. Such mentally performed transformations after sequential observation of the individual two-dimensional slices (i.e., MRI and angiography) may be virtual tasks that are very difficult or sometimes impossible to achieve. Using 3-D MRI data sets and a semiautomatic computer assisted segmentation technique, we tried to simulate intraoperative situs-based 3-D MRI reconstructions of parasagittal and parafalcine central region tumors. The MRI reconstructions were integrated into the neurosurgical planning procedure as an additional tool. They proved to be an important adjunct in determining the distinct anatomy of the intracranial pathology in its relation to the surrounding and overlying brain and vascular (especially venous) anatomy. With 10 patients with central region parasagittal and parafalcine tumors, we found that the 3-D MRI reconstructions revealed additional information compared to conventional cross-sectional images and had an influence on neurosurgical planning and strategy, improving neurosurgical performance and patient outcome.

Photodynamic therapy in neurosurgery: a review.

Photodynamic therapy (PDT) has been investigated extensively, both experimentally and clinically, as an adjunctive treatment in the neuro-oncological field. It is based on the more selective accumulation of a photosensitizer in malignant than normal tissue with low systemic toxicity. Subsequent light activation induces photo-oxidation, followed by selective tumour destruction via vascular and direct cellular mechanisms. Malignant brain tumours carry a lethal prognosis with a median survival of 15 months despite surgery, radiotherapy and chemotherapy. PDT is therefore a logical therapeutic concept for brain tumours infiltrating into normal brain. In this review, all the available data on patients treated with haematoporphyrin derivative-mediated PDT are critically analysed. Over 310 patients have been reported in the literature suffering from primary or recurrent malignant brain tumours which were treated with PDT following tumour resection in open clinical phase I/II trials. This number includes 58 patients treated at our own institution. Variations in the treatment protocols make evaluation scientifically difficult; however, there is a clear trend of increased median survival after surgical resection and one single photodynamic treatment. PDT is generally well tolerated and side effects consist of moderate increased intracranial pressure and prolonged skin sensitivity to direct sunlight. The current available data indicate that PDT is a safe treatment, which is well tolerated by the patients and yields an improvement in survival of those with malignant brain tumours. Conclusive information can be expected from controlled clinical trials which are currently being designed. The results raise the hope that PDT will be a valuable addition to the armamentarium for the treatment of cerebral malignancies.

Quadriplegia after lumbar disc surgery. A case report.

STUDY DESIGN: Case report. OBJECTIVE: To report a case of quadriplegia after surgery in the prone position for a herniated lumbar disc. SUMMARY OF BACKGROUND DATA: Ischemia in the vascular territories of the vertebral arteries after back surgery in the prone position is rare. Degenerative changes of the cervical spine or decreased blood flow to the head with mechanical vessel obstruction during extreme neck movements, systemic hypotension, and thromboembolism have mostly been implicated in the pathogenesis. METHODS: The case of a 33-year-old man undergoing surgery for an unilateral single level disc herniation at L4-L5 is presented. Within a few hours after surgery he developed quadriplegia and signs of occipital lobe dysfunction. He underwent magnetic resonance imaging investigation. Therapy included arterial blood pressure control, low molecular dextran, dexamethasone, bladder catheterization, and physiotherapy. RESULTS: Magnetic resonance imaging demonstrated intramedullary ischemic changes in the cervical spinal cord and at the borderline between anterior and posterior circulation. Outcome after 2 years is fair regarding the severe initial deficit-the patient walks alone with a cane and bladder function is under control. He is employed in a sedentary job. CONCLUSIONS: The authors believe that a temporary mechanical occlusion of a vertebral artery led to stasis, formation of thrombi, and subsequent embolism in the vertebrobasilar vascular territory. Extreme head rotation and neck extension is to be avoided in the prone position.

Therapy of glioblastoma multiforme: a cumulative experience of 10 years.

PURPOSE: Comparison of the effect of different therapeutic modalities on survival time of patients with glioblastoma multiforme operated on during the last decade (1980-1990). PATIENTS AND METHODS: The records of 157 consecutive patients with the histological diagnosis of glioblastoma multiforme were analysed for survival with respect to age of patients, extent of surgery, influence of re-operation and adjuvant postoperative treatment. The latter included fractionated radiotherapy, chemotherapy (BCNU. CCNU with Vincristine) and photodynamic therapy (PDT). RESULTS: Analysis of variance showed a significant effect for survival after macroscopically radical surgery (p = 0.005), postoperative radiotherapy (p < 0.001), chemotherapy (p < 0.01). Low age (p < 0.05) and a postoperative Karnofsky performance score (KPS) > or = 60 (p < 0.001) had a positive influence: the site of tumour and pre-operative presence of seizures had no significant influence (p > 0.1) on survival time. CONCLUSION: We conclude that the current adequate management of glioblastoma multiforme should include surgical resection followed by adjuvant treatment such as radiotherapy and chemotherapy.