Search

Rationale: A well-known clinical paradox is that severe bacterial infections persist in the lungs of patients with cystic fibrosis (CF) despite the abundance of polymorphonuclear neutrophils (PMN) and the presence of a high concentration of human neutrophil peptides (HNP), both of which are expected to kill the bacteria but fail to do so. The mechanisms remain unknown.Objectives: This study examined several possible mechanisms to understand this paradox.Methods: PMN were isolated from sputum and blood of subjects with and without CF or non-CF bronchiectasis for phagocytic assays. HNP isolated from patients with CF were used to stimulate healthy PMN followed by phagocytic tests.Measurements and Main Results: PMN isolated from the sputum of the bronchiectatic patients display defective phagocytosis that correlated with high concentrations of HNP in the lung. When healthy PMN were incubated with HNP, decreased phagocytic capacity was observed in association with depressed surface Fc gamma RIII, actin-filament remodeling, enhanced intracellular Ca(2+), and degranulation. Treatment of PMN with an intracellular Ca(2+) blocker or alpha1-proteinase inhibitor to attenuate the activity of HNP largely prevented the HNP-induced phagocytic deficiency. Intratracheal instillation of HNP in Pallid mice (genetically deficient in alpha1-proteinase inhibitor) resulted in a greater PMN lung infiltration and phagocytic deficiency compared with wild-type mice.Conclusions: HNP or PMN alone exert antimicrobial ability, which was lost as a result of their interaction. These effects of HNP may help explain the clinical paradox seen in patients with inflammatory lung diseases, suggesting HNP as a novel target for clinical therapy. [ABSTRACT FROM AUTHOR]

Background: The 6-minute walking test (6WT) has previously shown to be reliable and valid outcome measure in patients undergoing surgery for degenerative lumbar disorders (DLD). A role of 6WT in conservatively treated patients undergoing epidural steroid injection (ESI) remains unclear., Methods: About 50 patients with DLD, scheduled for ESI were assessed by the smartphone-based 6WT and common paper-based patient-reported outcome measures (PROMs), including the Core Outcome Measures Index [COMI] back, Oswestry Disability Index (ODI) and Short Form Survey (SF-12). Pearson correlation coefficient (PCC) was used to define the relationship between 6WT and PROMs. Reliability of the 6WT was determined by intraclass correlation coefficient (ICC). Age- and sex-adjusted objective functional impairment (OFI) z-scores were calculated for each patient., Results: A total of 50 patients (mean age 52 years, SD 13; 25% female), including 35 patients (70%) with lumbar disc herniation and 15 patients (30%) with lumbar spinal stenosis were included. The mean 6-minute walking distance (6WD) was 454.1 m (SD 89.1); the age- and sex-adjusted mean OFI z-score was -2.1 (SD 4.0). A total of 17 (34%) patients had mild, 8 (16%) moderate, and 4 (8%) severe OFI, while 21 (42%) had 6WT results within the normal population range (no OFI). The PCCs between the 6WD and VAS back pain were r=-0.30, ODI r=-0.43, COMI back r=-0.36, and PCS-12 r=0.51 (all p<.05). The ICC of the 6WT was β=0.92., Conclusions: This external validation in a patient cohort with DLD, which was managed conservatively, confirms the reliability and content validity of the 6WT with similar PCCs with PROMs compared to the original surgical cohort. The results confirm the 6WT as a valid and useful tool for assessing OFI in patients with DLD and a broad range of functional restrictions in an outpatient setting., Competing Interests: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (© 2024 The Authors.)

Background: Advancements in metastatic breast cancer (BC) treatment have enhanced overall survival (OS), leading to increased rates of brain metastases (BM). This study analyzes the association between microsurgical tumor reduction and OS in patients with BCBM, considering tumor molecular subtypes and perioperative treatment approaches., Methods: Retrospective analysis of surgically treated patients with BCBM from two tertiary brain tumor Swiss centers. The association of extent of resection (EOR), gross-total resection (GTR) achievement, and postoperative residual tumor volume (RV) with OS and intracranial progression-free survival (IC-PFS) was evaluated using Cox proportional hazard model., Results: 101 patients were included in the final analysis, most patients (38%) exhibited HER2-/HR + BC molecular subtype, followed by HER2 + /HR + (25%), HER2-/HR- (21%), and HER2 + /HR- subtypes (13%). The majority received postoperative systemic treatment (75%) and radiotherapy (84%). Median OS and intracranial PFS were 22 and 8 months, respectively. The mean pre-surgery intracranial tumor volume was 26 cm 3 , reduced to 3 cm 3 post-surgery. EOR, GTR achievement and RV were not significantly associated with OS or IC-PFS, but higher EOR and lower RV correlated with extended OS in patients without extracranial metastases. HER2-positive tumor status was associated with longer OS, extracranial metastases at BM diagnosis and symptomatic lesions with shorter OS and IC-PFS., Conclusions: Our study found that BC molecular subtypes, extracranial disease status, and BM-related symptoms were associated with OS in surgically treated patients with BCBM. Additionally, while extensive resection to minimize residual tumor volume did not significantly affect OS across the entire cohort, it appeared beneficial for patients without extracranial metastases., (© 2024. The Author(s).)

The current study addresses the question of whether the resection of more than one BM by multiple craniotomies within the same operation is associated with more adverse events (AEs) and worse functional outcome compared to cases in which only one BM was resected. All patients who underwent more than one craniotomy for resection of multiple BM at two Swiss tertiary neurosurgical care centers were included. Any AEs, functional outcome, and overall survival (OS) were analyzed after 1:1 propensity score matching with patients who underwent removal of a single BM only. A total of 94 patients were included in the final study cohort (47 of whom underwent multiple craniotomies). There was no significant difference in the incidence of AEs between the single and the multiple craniotomy group (n = 2 (4.3%) vs. n = 4 (8.5%), p = .7). Change in modified Rankin Scale (mRS) and Karnofsky Performance Status (KPS) at discharge demonstrated that slightly more single craniotomy patients improved in mRS, while the proportion of patients who worsened in mRS (16.3 vs. 16.7%) and KPS (13.6 vs. 15.2%) was similar in both groups (p = .42 for mRS and p = .92 for KPS). Survival analysis showed no significant differences in OS between patients with single and multiple craniotomies (p = .18). Resection of multiple BM with more than one craniotomy may be considered a safe option without increased AEs or worse functional outcome., (© 2024. The Author(s).)

Objective: Endovascular and microsurgical treatment are viable options for the majority of Borden type III dural arteriovenous fistulas (dAVFs). The aim of this study was to examine treatment outcomes in a comparative analysis of endovascular and surgical treatment modalities for Borden type III fistulas and explore clinical implications of the DES scheme in selecting ideal candidates for surgical therapy., Methods: Patients diagnosed with dAVFs with leptomeningeal venous drainage admitted to the Departments of Neurosurgery or Neuroradiology of the University Hospital Zurich between January 2014 and October 2021 were included in this study. Comprehensive patient data including demographics, clinical presentation, and dAVF characteristics, including established classifications, were collected. Treatment outcomes were assessed based on postinterventional angiography findings. In addition, treatment-related complications were assessed based on the Clavien-Dindo classification., Results: Among all Borden type III dAVFs, 15 were initially treated endovascularly (60% complete occlusion rate) and 10 with microsurgical disconnection (90% complete occlusion rate) (p = 0.18). Subgroup analysis of dAVFs meeting the criteria for directness and exclusivity based on the DES scheme showed a 100% complete occlusion rate after microsurgical disconnection, whereas embolization achieved a complete occlusion rate of 60% (p = 0.06). There was no significant difference in the rate or severity of treatment-related complications between treatment modalities., Conclusions: This study suggests that microsurgical disconnection is a viable primary treatment modality for Borden type III dAVFs, particularly for dAVFs that meet the criteria of directness and exclusivity according to the DES scheme. The DES scheme demonstrates its relevance in selecting the most appropriate treatment strategy for affected patients.

Purpose: Intraoperative ultrasonography (ioUS) is an established tool for the real-time intraoperative orientation and resection control in intra-axial oncological neurosurgery. Conversely, reports about its implementation in the resection of vestibular schwannomas (VS) are scarce. The aim of this study is to describe the role of ioUS in microsurgical resection of VS., Methods: ioUS (Craniotomy Transducer N13C5, BK5000, B Freq 8 MHz, BK Medical, Burlington, MA, USA) is integrated into the surgical workflow according to a 4-step protocol (transdural preresection, intradural debulking control, intradural resection control, transdural postclosure). Illustrative cases of patients undergoing VS resection through a retrosigmoid approach with the use of ioUS are showed to illustrate advantages and pitfalls of the technique., Results: ioUS allows clear transdural identification of the VS and its relationships with surgically relevant structures of the posterior fossa and of the cerebellopontine cistern prior to dural opening. Intradural ioUS reliably estimates the extent of tumor debulking, thereby helping in the choice of the right moment to start peripheral preparation and in the optimization of the extent of resection in those cases where subtotal resection is the ultimate goal of surgery. Transdural postclosure ioUS accurately depicts surgical situs., Conclusion: ioUS is a cost-effective, safe, and easy-to-use intraoperative adjunctive tool that can provide a significant assistance during VS surgery. It can potentially improve patient safety and reduce complication rates. Its efficacy on clinical outcomes, operative time, and complication rate should be validated in further studies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: Assessment of pituitary adenoma (PA) volume and extent of resection (EOR) through manual segmentation is time-consuming and likely suffers from poor interrater agreement, especially postoperatively. Automated tumor segmentation and volumetry by use of deep learning techniques may provide more objective and quick volumetry., Methods: We developed an automated volumetry pipeline for pituitary adenoma. Preoperative and three-month postoperative T1-weighted, contrast-enhanced magnetic resonance imaging (MRI) with manual segmentations were used for model training. After adequate preprocessing, an ensemble of convolutional neural networks (CNNs) was trained and validated for preoperative and postoperative automated segmentation of tumor tissue. Generalization was evaluated on a separate holdout set., Results: In total, 193 image sets were used for training and 20 were held out for validation. At validation using the holdout set, our models (preoperative / postoperative) demonstrated a median Dice score of 0.71 (0.27) / 0 (0), a mean Jaccard score of 0.53 ± 0.21/0.030 ± 0.085 and a mean 95 th percentile Hausdorff distance of 3.89 ± 1.96./12.199 ± 6.684. Pearson's correlation coefficient for volume correlation was 0.85 / 0.22 and -0.14 for extent of resection. Gross total resection was detected with a sensitivity of 66.67% and specificity of 36.36%., Conclusions: Our volumetry pipeline demonstrated its ability to accurately segment pituitary adenomas. This is highly valuable for lesion detection and evaluation of progression of pituitary incidentalomas. Postoperatively, however, objective and precise detection of residual tumor remains less successful. Larger datasets, more diverse data, and more elaborate modeling could potentially improve performance., (© 2023. The Author(s).)

Background and Objectives: Burr hole trepanation to evacuate chronic subdural hematoma (cSDH) results in bony skull defects that can lead to skin depressions. We intend to study the effect of burr hole covers to prevent skin depressions and improve the esthetic result., Methods: In a randomized trial, we enrolled adult patients with symptomatic cSDH. Patients received burr hole trepanation with (intervention) vs without burr hole covers (control) in a 1:1 ratio. Patients requiring evacuation of bilateral cSDHs served as their internal control. Primary outcome was satisfaction with the esthetic result of the scar, measured from 0 (dissatisfied) to 10 (very satisfied) on the Esthetic Numeric Analog (ANA) scale at 90 days. Secondary outcomes included ANA scale, rates of skin depression, complications, as well as neurological, disability, and health-related quality of life outcomes until 12 months., Results: We included 78 patients (55 with unilateral and 23 with bilateral cSDH; median age 78 years, 83% male) between 03/2019 and 05/2021, 50 trepanations for the intervention and 51 for the control group. In an intention-to-treat analysis, the ANA scale scores were 9.0 (intervention) and 8.5 (control arm) at 90 days (P = .498). At 12 months, the ANA scale scores were 9.0 and 8.0 for the intervention and control groups, respectively (P = .183). Skin depressions over the frontal burr hole were noted by 35% (intervention) and 63% (control) of patients at 90 days (P = .009) and by 35% and 79% (P < .001) at 12 months, respectively. There were no differences in complications, neurological, disability, and health-related quality of life outcomes., Conclusion: Satisfaction with the esthetic result of the scar was inherently high. This study does not show evidence for improvement on the ANA scale by applying a burr hole cover. The application of burr hole covers resulted in less skin depressions and did not negatively affect complication rates or outcomes., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Purpose: Microneurosurgical techniques have greatly improved over the past years due to the introduction of new technology and surgical concepts. To reevaluate the role of micro-neurosurgery in brain metastases (BM) resection in the era of new systemic and local treatment options, its safety profile needs to be reassessed. The aim of this study was to analyze the rate of adverse events (AEs) according to a systematic, comprehensive and reliably reproducible grading system after microneurosurgical BM resection in a large and modern microneurosurgical series with special emphasis on anatomical location., Methods: Prospectively collected cases of BM resection between 2013 and 2022 were retrospectively analyzed. Number of AEs, defined as any deviations from the expected postoperative course according to Clavien-Dindo-Grade (CDG) were evaluated. Patient, surgical, and lesion characteristics, including exact anatomic tumor locations, were analyzed using uni- and multivariate logistic regression and survival analysis to identify predictive factors for AEs., Results: We identified 664 eligible patients with lung cancer being the most common primary tumor (44%), followed by melanoma (25%) and breast cancer (11%). 29 patients (4%) underwent biopsy only whereas BM were resected in 637 (96%) of cases. The overall rate of AEs was 8% at discharge. However, severe AEs (≥ CDG 3a; requiring surgical intervention under local/general anesthesia or ICU treatment) occurred in only 1.9% (n = 12) of cases with a perioperative mortality of 0.6% (n = 4). Infratentorial tumor location (OR 5.46, 95% 2.31-13.8, p = .001), reoperation (OR 2.31, 95% 1.07-4.81, p = .033) and central region tumor location (OR 3.03, 95% 1.03-8.60) showed to be significant predictors in a multivariate analysis for major AEs (CDG ≥ 2 or new neurological deficits). Neither deep supratentorial nor central region tumors were associated with more major AEs compared to convexity lesions., Conclusions: Modern microneurosurgical resection can be considered an excellent option in the management of BM in terms of safety, as the overall rate of major AEs are very rare even in eloquent and deep-seated lesions., (© 2023. The Author(s).)

Introduction: Gross total resection (GTR), Biochemical Remission (BR) and restitution of a priorly disrupted hypothalamus pituitary axis (new improvement, IMP) are important factors in pituitary adenoma (PA) resection surgery. Prediction of these metrics using simple and preoperatively available data might help improve patient care and contribute to a more personalized medicine., Research Question: This study aims to develop machine learning models predicting GTR, BR, and IMP in PA resection surgery, using preoperatively available data., Material and Methods: With data from patients undergoing endoscopic transsphenoidal surgery for PAs machine learning models for prediction of GTR, BR and IMP were developed and externally validated. Development was carried out on a registry from Bologna, Italy while external validation was conducted using patient data from Zurich, Switzerland., Results: The model development cohort consisted of 1203 patients. GTR was achieved in 207 (17.2%, 945 (78.6%) missing), BR in 173 (14.4%, 992 (82.5%) missing) and IMP in 208 (17.3%, 167 (13.9%) missing) cases. In the external validation cohort 206 patients were included and GTR was achieved in 121 (58.7%, 32 (15.5%) missing), BR in 46 (22.3%, 145 (70.4%) missing) and IMP in 42 (20.4%, 7 (3.4%) missing) cases. The AUC at external validation amounted to 0.72 (95% CI: 0.63-0.80) for GTR, 0.69 (0.52-0.83) for BR, as well as 0.82 (0.76-0.89) for IMP., Discussion and Conclusion: All models showed adequate generalizability, performing similarly in training and external validation, confirming the possible potentials of machine learning in helping to adapt surgical therapy to the individual patient., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Recent therapeutic advances in metastatic melanoma have led to improved overall survival (OS) rates, with consequently an increased incidence of brain metastases (BM). The role of BM resection in the era of targeted and immunotherapy should be reassessed. In the current study we analysed the role of residual intracranial tumour load in a cohort of melanoma BM patients., Methods: Retrospective single-centre analysis of a prospective registry of resected melanoma BM from 2013 to 2021. Correlations of residual tumour volume and outcome were determined with respect to patient, tumour and treatment regimens characteristics., Results: 121 individual patients (66% male, mean age 59.9 years) were identified and included in the study. Pre- and postoperative systemic treatments included BRAF/MEK inhibitors, as well as combination or monotherapy of immune-checkpoint inhibitors (ICIs). Median OS of the entire cohort was 20 months. Cox proportional-hazard analysis revealed postoperative anti-CTLA4+anti-PD-1 therapy (HR 0.07, p = .01) and postoperative residual intracranial tumour burden (HR 1.4, p = .027) as significant predictors for OS. Further analysis revealed that ICI-naïve patients with residual tumour volume ≤3.5 cm 3 and postoperative ICI showed significantly prolonged OS compared to patients with residual volume >3.5 cm 3 (p < .0001). Subgroup analysis of ICI-naïve patients showed steroid intake postoperatively to be negatively associated with OS, however residual tumour volume ≤3.5 cm 3 remained independently correlated with superior OS (HR 0.14, p < .001)., Conclusion: Besides known predictive factors like postoperative ICI, a maximal intracranial tumour burden reduction seems to be beneficial, especially in ICI-naïve patients. This highlights the importance of local CNS control and the need to further investigating the role of initial surgical tumour load reduction in randomised clinical trials., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RD has intermittent, project focused consulting and/or advisory relationships with Novartis, Merck Sharp & Dhome (MSD), Bristol-Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, T3 Pharma, MaxiVAX SA, Pfizer and touchIME outside the submitted work. MW has received research grants from Apogenix, Merck, Sharp & Dohme, Merck (EMD), Philogen and Quercis, and honoraria for lectures or advisory board participation or consulting from Adastra, Bayer, Bristol Meyer Squibb, Medac, Merck, Sharp & Dohme, Merck (EMD), Nerviano Medical Sciences, Novartis, Orbus, Philogen and yMabs outside the submitted work. All remaining authors have declared no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Maximum safe resection followed by chemoradiotherapy as current standard of care for WHO grade III and IV gliomas can be influenced by the occurrence of perioperative adverse events (AE). The aim of this study was to determine the association of AE with the timing and choice of subsequent treatments as well as with overall survival (OS)., Methods: Prospectively collected data of 283 adult patients undergoing surgery for WHO grade III and IV gliomas at the University Hospital Zurich between January 2013 and June 2017 were analyzed. We assessed basic patient characteristics, KPS, extent of resection, and WHO grade, and we classified AE as well as modality, timing of subsequent treatment (delay, interruption, or non-initiation), and OS., Results: In 117 patients (41%), an AE was documented between surgery and the 3-month follow-up. There was a significant association of AE with an increased time to initiation of subsequent therapy (p = 0.005) and a higher rate of interruption (p < 0.001) or non-initiation (p < 0.001). AE grades correlated with time to initiation of subsequent therapy (p = 0.038). AEs were associated with shorter OS in univariate analysis (p < 0.001)., Conclusion: AEs are associated with delayed and/or altered subsequent therapy and can therefore limit OS. These data emphasize the importance of safety within the maximum-safe-resection concept., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Weber, Padevit, Müller, Velz, Vasella, Voglis, Gramatzki, Weller, Regli, Sarnthein and Neidert.)

Introduction: Postoperative imaging after neurosurgical interventions is usually performed in the first 72 hours after surgery to provide an accurate assessment of postoperative resection status. Patient frequently report that early postoperative examination after craniotomy for tumour and vascular procedures is associated with distress, exertion, nausea and pain. Delayed postoperative imaging (between 36 and 72 hours postoperatively) may have an advantage regarding psychological and physical stress compared with early imaging. The goal of this study is to evaluate and determine the optimal time frame for postoperative imaging with MRI and CT in terms of medical and neuroradiological implications and patient's subjective stress level., Methods and Analysis: Data will be prospectively collected from all patients aged 18-80 years who receive postoperative MRI or CT imaging following a craniotomy for resection of a cerebral tumour (benign and malignant) or vascular surgery. Participants have to complete questionnaires containing visual analogue scores (VAS) for headache and nausea, Body Part Discomfort score and a single question addressing subjective preference of timing of postoperative imaging after craniotomy. The primary endpoint of the study is the difference in subjective stress due to imaging studies after craniotomy, measured just before and after postoperative MRI or CT with the above-mentioned instruments. Subjective stress is defined as a combination of the scores VAS pain, VAS nausea and 0.5* Body Part Discomfort core.This study determines whether proper timing of postoperative imaging can improve patient satisfaction and reduce pain, stress and discomfort caused by postoperative imaging. Factors causing additional postoperative stress are likely responsible for delayed recovery of neurosurgical patients., Ethics and Dissemination: The institutional review board (Kantonale Ethikkommission Zürich) approved this study on 4 August 2020 under case number BASEC 2020-01590. The authors are planning to publish the data of this study in a peer-reviewed paper. After database closure, the data will be exported to the local data repository (Zurich Open Repository and Archive) of the University of Zurich. The sponsor (LR) and the project leader (MR.G) will make the final decision on the publication of the results. The data that support the findings of this study are available on request from the corresponding author LT. The data are not publicly available due to privacy/ethical restrictions., Trial Registration Number: NCT05112575; ClinicalTrials.gov., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Several microsurgical techniques are available for the decompression of lumbar spinal stenosis (LSS). More recently, a spinous process-splitting laminectomy (SPSL) technique was introduced, with the premise of diminishing paraspinal muscle damage. This study aims to compare the neurologic and functional outcomes, as well as the differences in early postoperative pain and analgesic use during hospitalization after conventional decompression (CD) versus SPSL surgery for LSS., Methods: Single-center retrospective analysis of all spinal decompression procedures (CD or SPSL) that were performed or supervised by one consulting spine surgeon, performed for LSS between 2015 and 2020. Preoperative neurologic symptoms, functional outcomes, as well as perioperative analgesic use and reported pain scales during hospitalization were analyzed., Results: From a total of 106 patients, 58 were treated using CD and 48 using SPSL. In both groups, around one-third of the patients were taking opiates preoperatively (38% for CD, 31% for SPSL). Patients submitted to SPSL reported more pain on first postoperative day but significantly less pain in the further postoperative course (day 3 numeric rating scale [NRS] 2.4 vs. 3.4, P = 0.03 and on day 5 NRS 2.5 vs. 3.7, P = 0.009). Equal or less cumulative doses of analgesics were administered postoperatively (significantly less paracetamol on day 5 compared with CD; P = 0.013). Both groups showed a similarly favorable outcome in terms of improved mobility and there were no significant differences between complications and re-stenosis rates between both techniques., Conclusions: Patients treated with SPSL technique for LSS showed an equivalent favorable functional outcome compared to CD. However, SPSL patients showed significantly less subacute postoperative pain while using equal amounts or fewer analgesics postoperatively., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

A nuclear protein of testis (NUT) carcinoma, also known as NUT midline carcinoma, is a rare subtype of squamous carcinoma known for its aggressive growth behaviour. It can form anywhere in the body. Although, it usually occurs along midline structures (head, neck, lungs). The authors present the first report of intrasellar NUT carcinoma with cavernous sinus infiltration in a 47-year-old patient. MRI showed an inhomogeneous, gadolinium-enhancing lesion with intra- and suprasellar growth, invasion of the cavernous sinus without clear differentiation from normal pituitary tissue. Given the lymphoma diagnosis in the frozen section and invasion of the cavernous sinus, the patient underwent endoscopic, transnasal, and transsphenoidal subtotal resection only. Local tumour and spinal metastases showed a good response to radio-chemotherapy. Despite combined radio-chemotherapy, the patient died of pulmonary insufficiency due to rapid progression of pulmonary metastasis 6 months after the initial diagnosis., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Introduction: Outcome assessments after surgery for degenerative lumbar disorders (DLDs) rely on subjective patient-reported outcomes (PROMs). New objective functional capacity tests, like the smartphone-based 6-min walking test (6WT), have been introduced but presumably also do not reflect the patient's real-life functional performance., Research Question: Pilot study to analyze changes in smartphone-based real-life activity data for physical performance outcome in patients undergoing surgery for DLD., Material and Methods: Prospective observational study of DLD patients. Objective functional capacity and subjective outcomes were measured using 6WT and PROMs. Real-life physical performance data were acquired retrospectively using Apple iPhone Health data and compared against objective capacity and subjective outcomes., Results: Eight patients (mean 46 years, 62% male) provided 286.858 smartphone mile counts. PROMs and physical capacity (6WT) significantly improved postoperatively. 6WT results increased from 352m pre-to 555/567m at 6/12 weeks postoperatively (p ​= ​0.03). For physical performance a linear mixed effect models showed an increase in daily distance in the first 4 months after surgery (slope +0.178; p ​< ​0.001). However, those increases reversed from 4 until 12 months postoperatively (negative slope estimate of -0.076; p ​< ​0.001). Smartphone-derived physical performance measures showed a positive correlation with corresponding physical capacity in the 6WT (R ​= ​0.57,p ​= ​0.004) and negative correlations with PROMs (COMI: R ​= ​-0.62p ​= ​0.001; ZCQ-Physical-Function: R ​= ​-0.68,p ​< ​0.001; ZCQ-Symptom-Severity: R ​= ​-0.52,p ​= ​0.009)., Discussion and Conclusion: Smartphone-based real-life activity data allows for longitudinal physical performance assessment. Physical performance correlated with physical capacity and patient's subjective perception of disability. However, physical performance may be more resistant to postoperative longtime change which should consult a more cautious use as objective outcome measure., (© 2022 The Authors.)

Introduction: Hereditary transthyretin amyloidosis (ATTRv) is an autosomal-dominant disorder, where a TTR mutations lead to amyloid fibril deposits in tissues and consecutively alter organ function. ATTRv is a multisystemic disorder with a heterogeneous clinical presentation. Spinal leptomeningeal depositions are described only scarcely in the literature., Research Question: We present a rare case of surgically treated intradural, extra-medullary amyloidosis with respective clinical, diagnostic and surgical features to raise awareness of this rare entity., Material and Methods: Clinical, radiological and operative characteristics were retrieved from the electronical patient management system. Additionally, a scoping literature review on leptomeningeal spinal manifestations of ATTRv was performed., Results: A 45-year-old man with a known ATTRv presented with gait disturbance and paresis of the lower extremities. He had been treated with the siRNA therapeutical Patisiran for 13 months under which his symptoms worsened. An MRI of the spine revealed spinal cord compression with myelopathy at the level of T2 with anterior dislocation of the spinal cord due to an intradural, extramedullary lesion. A laminectomy and opening of the dura with a complete resection of the lesion was performed. The histological examination of the biopsy showed amyloid deposits. At six-month follow-up the patient showed complete normalization of the paresis, gait, sensory and urinary disturbances and resumed his work., Discussion and Conclusion: Spinal leptomeningeal deposition of amyloid is a rare occurrence within the framework of ATTRv. Micro-neurosurgical complete resection of the lesion is feasible in patients with preoperative myelopathic symptoms and resulted in complete symptom relief in this case., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Introduction: Ever since the beginning of cerebral bypass surgery, the role of the bypass has been debated and indications have changed over the last 5 decades. This systematic literature research analysed all clinical studies on cerebral bypass that have been published from January 1959 to January 2020 for their year of publication, country of origin, citation index, role of and indication for bypass, bypass technique, revascularized territory, flow capacity, and title (for word cloud analysis per decade)., Methods: A systematic literature research was conducted using PubMed, Web of Science, EMBASE, and SCOPUS databases. All studies that have been published until January 1, 2020, were included., Results: Of 6,013 identified studies, 2,585 were included in the analysis. Of these, n = 1,734 (67%) studies addressed flow-augmentation bypass and n = 701 (27%) addressed flow-preservation bypass. The most common indication reported for flow augmentation is moyamoya (n = 877, 51%), followed by atherosclerotic steno-occlusive disease (n = 753, 43%). For flow preservation, the most common indication is studies reporting on cerebral aneurysm surgery (n = 659, 94%). The increasing popularity of reporting on these bypass operations almost came to an end with the FDA approval of flow diverters for aneurysm treatment in 2011. Japan is the country with the most bypass studies (cumulatively published 933 articles), followed by the USA (630 articles) and China (232 articles)., Discussion/conclusion: Clinical studies on cerebral bypass surgery have become increasingly popular in the past decades. Since the introduction of moyamoya as a distinct pathologic entity, Asian countries in particular have a very active community regarding this disease, with an increasing number of articles published every year. Studies on bypass for chronic steno-occlusive disease peaked in the 1980s but have remained the main focus of bypass research, particularly in many European departments. The number of reports published on these bypass operations significantly decreased after the FDA approval of flow diverters for aneurysm treatment in 2011., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Background Context: Spinal arachnoid web (SAW) is a rare condition characterized by focal thickening of the arachnoid membrane causing displacement and compression of the spinal cord with progressive symptoms and neurological deficits. Recent reports and clinical experience suggest that SAW is a distinct entity with specific radiological findings and treatment strategies distinguishable from other arachnopathies and potential differential diagnoses., Purpose: To better define the diagnostic and clinical features, treatment options and outcomes of surgically treated SAW., Study Design: Multicentric retrospective cohort study., Patient Sample: Twelve cases of SAW surgically treated at three different centers., Outcome Measures: Self-reported and neurological outcome measurements (pain, sensory-motor deficits, vegetative dysfunctions) were assessed at follow-up timepoints., Methods: Retrospective review of prospectively collected data on all patients surgically treated for SAW from three participating neurosurgical centers between 2014 and 2020. Clinicopathological data, including neurological presentation, radiological and histological findings and outcome data were analyzed., Results: Twelve radiologically and surgically confirmed cases of SAW were analyzed. Mean patient age was 54.7 [±12.7], 67% were male. All SAWs were located in the posterior thoracic dural sac. On magnetic resonance imaging (MRI), the "scalpel sign" - a characteristic focal dorsal indentation of the spinal cord resembling a scalpel blade - was identified in all patients. A focal intramedullary syrinx was present in 83%. Preoperative clinical symptoms included signs of myelopathy, pain, weakness and sensory loss, most commonly affecting the trunk/upper back or lower extremities. Laminectomy or laminoplasty with intradural excision of the SAW was the surgical treatment of choice in all cases. Intraoperative ultrasound was valuable to visualize the cerebrospinal fluid (CSF) flow obstruction, confirm the SAW location before dura incision and to control adequacy of resection. After surgery, sensory loss and weakness in particular showed significant improvement., Conclusions: The present study comprises the largest series of surgically treated SAW, underscoring the unique clinical, radiographic, histopathological, and surgical findings. We want to emphasize SAW being a distinct entity of spinal arachnopathy with a favorable long-term outcome if diagnosed correctly and treated surgically. Intraoperative ultrasound aids visualizing the SAW before dural incision, as well as verifying restored CSF flow after resection., Competing Interests: Declarations of competing interests The authors have no competing interests or financial disclosures in relation to this trial., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Intraoperatively acquired diffusion-weighted imaging (DWI) sequences in cranial tumor surgery are used for early detection of ischemic brain injuries, which could result in impaired neurological outcome and their presence might thus influence the neurosurgeon's decision on further resection. The phenomenon of false-negative DWI findings in intraoperative magnetic resonance imaging (ioMRI) has only been reported in single cases and therefore yet needs to be further analyzed. This retrospective single-center study's objective was the identification and characterization of false-negative DWI findings in ioMRI with new or enlarged ischemic areas on postoperative MRI (poMRI). Out of 225 cranial tumor surgeries with intraoperative DWI sequences, 16 cases with no additional resection after ioMRI and available in-time poMRI (< 14 days) were identified. Of these, a total of 12 cases showed false-negative DWI in ioMRI (75%). The most frequent tumor types were oligodendrogliomas and glioblastomas (4 each). In 5/12 cases (41.7%), an ischemic area was already present in ioMRI, however, volumetrically increased in poMRI (mean infarct growth + 2.1 cm 3 ; 0.48-3.6), whereas 7 cases (58.3%) harbored totally new infarcts on poMRI (mean infarct volume 0.77 cm 3 ; 0.05-1.93). With this study we provide the most comprehensive series of false-negative DWI findings in ioMRI that were not followed by additional resection. Our study underlines the limitations of intraoperative DWI sequences for the detection and size-estimation of hyperacute infarction. The awareness of this phenomenon is crucial for any neurosurgeon utilizing ioMRI., (© 2021. The Author(s).)

Intraoperative MRI (ioMRI) has become a frequently used tool to improve maximum safe resection in brain tumor surgery. The usability of intraoperatively acquired diffusion-weighted imaging sequences to predict the extent and clinical relevance of new infarcts has not yet been studied. Furthermore, the question of whether more aggressive surgery after ioMRI leads to more or larger infarcts is of crucial interest for the surgeons' operative strategy. Retrospective single-center analysis of a prospective registry of procedures from 2013 to 2019 with ioMRI was used. Infarct volumes in ioMRI/poMRI, lesion localization, mRS, and NIHSS were analyzed for each case. A total of 177 individual operations (60% male, mean age 45.5 years old) met the inclusion criteria. In 61% of the procedures, additional resection was performed after ioMRI, which resulted in a significantly higher number of new ischemic lesions postoperatively (p < .001). The development of new or enlarged ischemic areas upon additional resection could also be shown volumetrically (mean volume in ioMRI 0.39 cm 3 vs. poMRI 2.97 cm 3 ; p < .001). Despite the surgically induced new infarcts, mRS and NIHSS did not worsen significantly in cases with additional resection. Additionally, new perilesional ischemia in eloquently located tumors was not associated with an impaired neurological outcome. Additional resection after ioMRI leads to new or enlarged ischemic areas. However, these new infarcts do not necessarily result in an impaired neurological outcome, even when in eloquent brain areas., (© 2020. The Author(s).)

Background: The most widely used classifications of adverse events (AEs) in neurosurgery define their severity according to the therapy used to treat them. This concept has substantial shortcomings because it does not reflect the severity of AEs that are not treated, such as new neurological deficits., Objective: To present a novel multidimensional and patient-centered classification of the severity of AE in neurosurgery and evaluate its applicability., Methods: The Therapy-Disability-Neurology (TDN) grading system classifies AEs depending on the associated therapy, disability, and neurological deficits. We conducted a 2-center retrospective observational study on 6071 interventions covering the whole neurosurgical spectrum with data prospectively recorded between 2013 and 2019 at 2 institutions from 2 countries., Results: Using the first patient cohort (4680 interventions), a positive correlation was found between severity of AE and LOS as well as treatment cost. Each grade was associated with a greater deterioration of the Karnofsky Performance Status Scale (KPS) at discharge and at follow-up. When using the same methods on the external validation cohort (1391 interventions), correlations between the grades of AE, LOS, and KPS at discharge were even more pronounced., Conclusion: Our results suggest that the TDN grade is consistent with clinical and economic repercussions of AE and thus reflects AE severity. It is easily interpreted and enables comparison between different medical centers. The standardized report of the severity of AE in the scientific literature could constitute an important step forward toward a more critical, patient-centered, and evidence-based decision-making in neurosurgery., (© Congress of Neurological Surgeons 2021.)

No abstract present., (© 2021 The Author(s). Published by IMR Press.)

Electrolyte disorders are relatively frequent and potentially serious complications after pituitary surgery. Both DI (diabetes insipidus) and SIADH (syndrome of inappropriate antidiuresis) can complicate and prolong hospital and intensive care unit stay, and the latter may even be preventable. We aim to assess the incidence of both electrolyte disorders and their risk factors. From a prospective registry of patients who underwent endoscopic transnasal transsphenoidal surgery (TSS) for pituitary adenoma, patients with postoperative DI and SIADH were identified. Univariable and multivariable statistics were carried out to identify factors independently associated with the occurrence of either DI or SIADH. A total of 174 patients were included, of which 73 (42%) were female. Mean age was 54 years (range 20-88). During postoperative hospital stay, 13 (7.5%) patients presenting with DI and 11 (6.3%) with SIADH were identified. Patients who developed DI after surgery had significantly longer hospital stays (p = 0.022), as did those who developed SIADH (p = 0.002). Four (2.3%) patients were discharged with a diagnosis of persistent DI, and 2 (1.1%) with the diagnosis of SIADH. At the last follow-up, 5 (2.9%) patients presented with persistent DI, while none of the patients suffered from SIADH. Younger age (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94-1.01, p = 0.166) and pituitary apoplexy (OR 2.69, 95% CI 0.53-10.65, p = 0.184) were weakly associated with the occurrence of DI. We identified younger age (OR 0.96, 95% CI 0.92-0.99, p = 0.045) and lower preoperative serum sodium (OR 0.83, 95% CI 0.71-0.95, p = 0.008) as independent risk factors for SIADH. Although we found a weak association among age, pituitary apoplexy, and the occurrence of DI, no independent predictor was identified for DI. For postoperative SIADH however, lower age and preoperative serum sodium were identified as significant predictors. None of these findings were sufficiently supported by preexisting literature. Both electrolyte disorders are exquisitely hard to predict preoperatively, and further research into their early detection and prevention is warranted.

Acute Traumatic Central Cord Syndrome: Etiology, Pathophysiology, Clinical Manifestation, and Treatment Abstract. The acute traumatic central cord syndrome (ATCCS) represents an injury to the spinal cord with disproportionately greater motor impairment of the upper than the lower extremities, with bladder dysfunction and with varying degrees of sensory loss below the level of the respective lesion. The mechanism of ATCCS is most commonly a traumatic hyperextension injury of the cervical spine at the base of an underlying spondylosis and spinal stenosis. The mean age is 53 years, and segments C4 to Th1 are most frequently affected. In addition to medical history and clinical examination, the definitive diagnosis is made by magnetic resonance imaging, where T2-hyperintense lesions are typically observed in the affected spinal cord segment. Surgical decompression (and fusion) of the respective segment is recommended to prevent repetitive trauma to the spinal cord and to stop progression of clinical symptoms. Patients with diagnosed ATCCS and who are treated adequately usually have a good prognosis.

Purpose: Hyponatremia after pituitary surgery is a frequent finding with potential severe complications and the most common cause for readmission. Several studies have found parameters associated with postoperative hyponatremia, but no reliable specific predictor was described yet. This pilot study evaluates the feasibility of machine learning (ML) algorithms to predict postoperative hyponatremia after resection of pituitary lesions., Methods: Retrospective screening of a prospective registry of patients who underwent transsphenoidal surgery for pituitary lesions. Hyponatremia within 30 days after surgery was the primary outcome. Several pre- and intraoperative clinical, procedural and laboratory features were selected to train different ML algorithms. Trained models were compared using common performance metrics. Final model was internally validated on the testing dataset., Results: From 207 patients included in the study, 44 (22%) showed a hyponatremia within 30 days postoperatively. Hyponatremic measurements peaked directly postoperatively (day 0-1) and around day 7. Bootstrapped performance metrics of different trained ML-models showed largest area under the receiver operating characteristic curve (AUROC) for the boosted generalized linear model (67.1%), followed by the Naïve Bayes classifier (64.6%). The discriminative capability of the final model was assessed by predicting on unseen dataset. Large AUROC (84.3%; 67.0-96.4), sensitivity (81.8%) and specificity (77.5%) with an overall accuracy of 78.4% (66.7-88.2) was reached., Conclusion: Our trained ML-model was able to learn the complex risk factor interactions and showed a high discriminative capability on unseen patient data. In conclusion, ML-methods can predict postoperative hyponatremia and thus potentially reduce morbidity and improve patient safety.

The respiratory rhythm and pattern and sympathetic and parasympathetic outflows are generated by distinct, though overlapping, propriobulbar arrays of neuronal microcircuit oscillators constituting networks utilizing mutual excitatory and inhibitory neuronal interactions, residing principally within the metencephalon and myelencephalon, and modulated by synaptic influences from the cerebrum, thalamus, hypothalamus, cerebellum, and mesencephalon and ascending influences deriving from peripheral stimuli relayed by cranial nerve afferent axons. Though the respiratory and cardiovascular regulatory effector mechanisms utilize distinct generators, there exists significant overlap and interconnectivity amongst and between these oscillators and pathways, evidenced reciprocally by breathing modulation of sympathetic oscillations and sympathetic modulation of neural breathing. These coupling mechanisms are well-demonstrated coordinately in sympathetic- and respiratory-related central neuronal and efferent neurogram recordings and quantified by the findings of cross-correlation, spectra, and coherence analyses, combined with empirical interventions including lesioning and pharmacological agonist and antagonist microinjection studies, baroloading, barounloading, and hypoxic and/or hypercapnic peripheral and/or central chemoreceptor stimulation. Sympathetic and parasympathetic central neuronal and efferent neural discharge recordings evidence classic fast rhythms produced by propriobulbar neuronal networks located within the medullary division of the lateral tegmental field, coherent with cardiac sympathetic nerve discharge. These neural efferent nerve discharges coordinately evidence slow synchronous oscillations, constituted by Traube Hering (i.e., high frequency), Mayer wave (i.e., medium or low frequency), and vasogenic autorhythmicity (i.e., very low frequency) wave spectral bands. These oscillations contribute to coupling neural breathing, sympathetic oscillations, and parasympathetic cardiovagal premotoneuronal activity. The mechanisms underlying the origins of and coupling amongst, these waves remains to be unresolved., Competing Interests: All authors declare no conflicts of interest., (© 2020 Ghali et al. Published by IMR press.)

Introduction: Outcomes rated on impairment scales are satisfactory after burr hole trepanation for chronic subdural haematoma (cSDH). However, the surgery leads to bony defects in the skull with skin depressions above that are frequently considered aesthetically unsatisfactory by the patients. Those defects could be covered by the approved medical devices (burr hole covers), but this is rarely done today. We wish to assess, whether the application of burr hole covers after trepanation for the evacuation of cSDH leads to higher patient satisfaction with the aesthetical result at 90 days postoperative, without worsening disability outcomes or increasing the complication rate., Methods and Analysis: This is a prospective, single-blinded, randomised, controlled, investigator-initiated clinical trial enrolling 80 adult patients with first-time unilateral or bilateral cSDH in Switzerland. The primary outcome is the difference in satisfaction with the aesthetic result of the scar, comparing patients allocated to the intervention (burr hole cover) and control (no burr hole cover) group, measured on the Aesthetic Numeric Analogue scale at 90 days postoperative. Secondary outcomes include differences in the rates of skin depression, complications, as well as neurological, disability and health-related quality of life outcomes until 12 months postoperative., Ethics and Dissemination: The institutional review board (Kantonale Ethikkommission Zürich) approved this study on 29 January 2019 under case number BASEC 2018-01180. This study determines, whether a relatively minor modification of a standard surgical procedure can improve patient satisfaction, without worsening functional outcomes or increasing the complication rate. The outcome corresponds to the value-based medicine approach of modern patient-centred medicine. Results will be published in peer-reviewed journals and electronic patient data will be safely stored for 15 years., Trial Registration Number: NCT03755349., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

IL-22 is a potent pro-inflammatory cytokine upregulated in psoriasis and in other inflammatory diseases. The function of IL-22 is regulated by the soluble scavenging receptor, IL-22 binding protein (IL-22BP or IL-22RA2). However, the role and regulation of IL-22BP itself in the pathogenesis of inflammatory disease remain unclear. We used the TLR7 agonist Imiquimod (IMQ) to induce a psoriasis-like skin disease in mice and found a strong downregulation of IL-22BP in the affected skin as well as in the lymph nodes of animals treated with IMQ. We also analysed psoriatic skin of patients and compared this to skin of healthy donors. Interestingly, IL-22BP expression was similarly downregulated in skin biopsies of psoriasis patients compared to the skin of healthy donors. Since IL-22BP is expressed foremost in dendritic cells, we characterized its expression in monocyte-derived dendritic cells (MoDC) during maturation. In this way, we found Prostaglandin E2 (PGE 2 ) to be a potent suppressor of IL-22BP expression in vitro. We conclude that regulation of IL-22BP by inflammatory mediators is an important step for the progression of inflammation in the skin and possibly also in other autoimmune diseases.

Human neutrophil peptides (HNP) exert immune-modulating effects. We hypothesized that HNP link innate and adaptive immunity through activation of costimulatory molecules. Human lung epithelial cells and CD4+ lymphocytes were treated with HNP separately or in coculture. Stimulation with HNP induced an increase in cell surface expression of CD54 (ICAM-1), CD80, and CD86 on lung epithelial cells and the corresponding major ligands, CD11a (LFA-1), CD152 (CTLA-4), and CD28 on CD4+ lymphocytes. There was an increased nuclear expression of the transcription factor p53 in human alveolar A549 cells and an elevated NF-kappaB (p50) and a degradation of I-kappaB protein in CD4+ lymphocytes following HNP stimulation. HNP enhanced the interaction between A549 cells and CD4+ lymphocytes by increasing cell adhesion and release of IFN-gamma, IL-2, and IL-8. This was attenuated by using an alpha1-proteinase inhibitor to neutralize HNP. We conclude that HNP play an important role in linking innate to acquired immunity by activation of costimulatory molecules in lung epithelial cells and CD4+ lymphocytes.

Antimicrobial human neutrophil peptides (HNPs) play a pivotal role in innate host defense against a broad spectrum of prokaryotic pathogens. In addition, HNPs modulate cellular immune responses by producing the chemokine interleukin-8 (IL-8) in myeloid and epithelial cells and by exerting chemotaxis to T cells, immature dendritic cells, and monocytes. However, the mechanisms by which HNPs modulate the immune responses in the eukaryotic cells remain unclear. We demonstrated that, as with adenosine triphosphate (ATP) and uridine diphosphate (UDP), HNP stimulation of human lung epithelial cells selectively induced IL-8 production in 10 pro- and anti-inflammatory cytokines examined. HNP-induced IL-8 release was inhibited by treatment with the nucleotide receptor antagonists suramin and reactive blue. Transfection of lung epithelial cells with antisense oligonucleotides targeting specific purinergic P2Y receptors revealed that the P2Y6 (ligand of UDP) signaling pathway plays a predominant role in mediating HNP-induced IL-8 production.

The mechanisms by which parenchymal cells interact with immune cells, particularly after removal of LPS, remain unknown. Lung explants from rats, mice deficient in the TNF gene, or human lung epithelial A549 cells were treated with LPS and washed, before naive alveolar macrophages, bone marrow monocytes, or PBMC, respectively, were added to the cultures. When the immune cells were cocultured with LPS-challenged explants or A549 cells, TNF production was greatly enhanced. This was not affected by neutralization of LPS with polymyxin B. The LPS-induced increase in the expression of ICAM-1 on A549 cells correlated with TNF production by PBMC. The cellular cross talk leading to the TNF response was blunted by an anti-ICAM-1 Ab and an ICAM-1 antisense oligonucleotide. In A549 cells, a persistent decrease in the concentration of intracellular cAMP was associated with colocalization of LPS into Toll-like receptor 4 and the Golgi apparatus, resulting in increased ICAM-1 expression. Inhibition of LPS internalization by cytochalasin D or treatment with dibutyryl cAMP attenuated ICAM-1 expression and TNF production by PBMC. In conclusion, lung epithelial cells are not bystanders, but possess memory of LPS through the expression of ICAM-1 that interacts with and activates leukocytes. This may provide an explanation for the failure of anti-LPS therapies in sepsis trials.

Rationale and Hypothesis: Acute lung injury is a frequent complication of severe sepsis or blood loss and is often associated with an excessive inflammatory response requiring mechanical ventilation. We tested the hypothesis that the types of fluids used during early resuscitation have an important effect on the evolution of lung injury., Methods: Rats were subjected to either hemorrhage or endotoxemia for 1 hr, followed by resuscitation to a controlled mean blood pressure with Ringer's lactate, 5% albumin, or 25% albumin for 1 hr. After resuscitation, blood cytokine levels were measured. The lung was then excised and ventilated with a tidal volume of 30 mL/kg for 2 hrs., Results: The volume of fluids required was significantly smaller in the albumin-treated groups than in the Ringer's lactate groups. In the hemorrhagic shock model, plasma concentrations of tumor necrosis factor-alpha, interleukin-6, and macrophage inflammatory protein-2 were significantly lower and interleukin-10 was significantly higher in the albumin-treated groups compared with the Ringer's lactate-treated group. The levels of tumor necrosis factor-alpha and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid were lower and interleukin-10 was higher in the albumin-treated groups than in the Ringer's lactate group. The decreased cytokine production was associated with a reduction of hydrogen peroxide formation with albumin resuscitation. The lung wet/dry ratio was lower in the 5% albumin (0.54 +/- 0.01) and 25% albumin (0.55 +/- 0.02) groups than in the Ringer's lactate group (0.62 +/- 0.02; both p <.05). These effects of albumin seen in the hemorrhagic shock model were not observed in the endotoxic shock model., Conclusions: We conclude that resuscitation with albumin may have utility in reducing ventilator-induced lung injury after hemorrhagic shock, but not after endotoxic shock. These findings suggest that the mechanisms leading to ventilator-induced lung injury after hemorrhage differ from those after endotoxemia.