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Subjective Social Status (SSS) reflects one's perceived rank within a given social structure and has been shown to be a unique correlate of physical and mental health. However, no research has been conducted to address populations of (recovering) critically ill patients. To shed light on the relationship between SSS and health in critically ill patients, we focus on survivors of acute respiratory distress syndrome (ARDS). A cohort study with N  = 877 ARDS survivors was conducted in 61 intensive care units (ICUs) in Germany between 2014 and 2019. Health-related quality of life (HRQoL, Physical and Mental Component Scale: PCS, MCS of the SF-12) and SSS (MacArthur Scale) were assessed at 12, 24, and 36 months after discharge from ICU. Objective social status (Socioeconomic status [SES]) was assessed once at ICU baseline. Bivariate correlations between SSS and HRQoL (PCS and MCS) remain significant throughout the study period ( r  = .29 - .50, all p-values < .05). Subsequent hierarchical regression shows that SSS remains predictive for PCS and MCS even after controlling for SES (β = .335 - .486, all p values < .001). The results indicate the importance (and unique contribution) of the subjective localization within the status hierarchy for long-term HRQoL after critical illness.

Aim: To analyze the association of individual pre-ICU risk factors (obesity, physical and mental comorbidity, smoking status) on the long-term recovery process in survivors of the acute respiratory distress syndrome (ARDS; outcomes: health related quality of life, health care utilization; measured at 12, 24, and 36 months after ICU discharge)., Findings: Results show a possible causal link between pre-ICU risk factors and subsequent recovery of survivors of ARDS, especially with regard to mental health related quality of life., Purpose: Identifying relevant pre-existing risk factors, such as mental health problems, will enable the identification of at-risk patients, thus aiding in the improvement of long-term healthcare for survivors of critical illness., (© 2024. The Author(s).)

Background: Several research has underlined the multi-system character of COVID-19. Though effects on the Central Nervous System are mainly discussed as disease-specific affections due to the virus' neurotropism, no comprehensive disease model of COVID-19 exists on a neurofunctional base by now. We aimed to investigate neuroplastic grey- and white matter changes related to COVID-19 and to link these changes to neurocognitive testings leading towards a multi-dimensional disease model., Methods: Groups of acutely ill COVID-19 patients (n = 16), recovered COVID-19 patients (n = 21) and healthy controls (n = 13) were prospectively included into this study. MR-imaging included T1-weighted sequences for analysis of grey matter using voxel-based morphometry and diffusion-weighted sequences to investigate white matter tracts using probabilistic tractography. Comprehensive neurocognitive testing for verbal and non-verbal domains was performed., Results: Alterations strongly focused on grey matter of the frontal-basal ganglia-thalamus network and temporal areas, as well as fiber tracts connecting these areas. In acute COVID-19 patients, a decline of grey matter volume was found with an accompanying diminution of white matter tracts. A decline in executive function and especially verbal fluency was found in acute patients, partially persisting in recovered., Conclusion: Changes in gray matter volume and white matter tracts included mainly areas involved in networks of executive control and language. Deeper understanding of these alterations is necessary especially with respect to long-term impairments, often referred to as 'Post-COVID'., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Deuter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Describe the long-term development of outcomes for survivors of the Acute Respiratory Distress Syndrome (ARDS)., Material and Methods: A cohort study with N = 877 ARDS survivors was conducted. Health related quality of life (HRQoL, Physical and Mental Component Scale: PCS, MCS of the SF-12), return to work (RtW), panic disorder, depressive symptoms (PHQD), and post-traumatic-stress-disorder (PTSD, PTSS-14) were assessed at 3, 6, 12, 24, and 36 months after discharge from ICU., Results: PCS, MCS, and RtW increased during the first 12 months [e.g. PCS: Md = 36 (IQR 31-43) at 3 months, Md = 42 (IQR 34-52) at 12 months; MCS: Md = 44 (IQR 32-54) at 3 months, Md = 47 (IQR 33-57) at 12 months, RtW = 23.2% at 3 months, 54.5% at 12 months], and remained relatively stable afterwards. Proportion of major depressive syndrome decreased from 3 (14.2%) to 36 months (8.9%). Proportions of panic disorder (5.3% to 7.4%) and PTSD (27.1% to 32.6%) varied only slightly., Conclusions: Most of recovery in HRQoL and RtW occur during the first 12 months, after which a plateau is reached, indicating a chronification for many patients. Contrary to this, however, psychopathological symptoms remain stable, except for depressive symptoms. [200 words]., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: The authors have disclosed no conflicts of interest.

Background: The acute respiratory distress syndrome (ARDS) is a life-threatening condition with the risk of developing hypoxia and thus requires for invasive mechanical ventilation a long-term analgosedation. Yet, prolonged analgosedation may be a reason for declining health-related quality of life (HRQoL) and the development of psychiatric disorders., Methods: We used data from the prospective observational nation‑wide ARDS study across Germany (DACAPO) to investigate the influence of sedation and analgesia on HRQoL and the risk of psychiatric symptoms in ARDS survivors 3, 6 and 12 months after their discharge from the intensive care unit (ICU). HRQoL was measured with the Physical and Mental Component Scale of the Short‑Form 12 Questionnaire (PCS‑12, MCS‑12). The prevalence of psychiatric symptoms (depression and post‑traumatic stress disorder [PTSD]) was assessed using the Patient Health Questionnaire‑9 and the Post‑Traumatic Stress Syndrome‑14. The associations of analgosedation with HRQoL and psychiatric symptoms were investigated by means of multivariable linear regression models., Results: The data of 134 ARDS survivors (median age [IQR]: 55 [44-64], 67% men) did not show any significant association between analgosedation and physical or mental HRQoL up to 1 year after ICU discharge. Multivariable linear regression analysis (B [95%‑CI]) yielded a significant association between symptoms of psychiatric disorders and increased cumulative doses of ketamine up to 6 months after ICU discharge (after 3 months: depression: 0.15 [0.05, 0.25]; after 6 months: depression: 0.13 [0.03, 0.24] and PTSD: 0.42 [0.04, 0.80)])., Conclusions: Up to 1 year after ICU discharge, analgosedation did not influence HRQoL of ARDS survivors. Prolonged administration of ketamine during ICU treatment, however, was positively associated with the risk of psychiatric symptoms. The administration of ketamine to ICU patients with ARDS should be with caution., Trial Registration: Clinicaltrials.gov: NCT02637011 (Registered 15 December 2015, retrospectively registered)., Competing Interests: CK reports personal fees from Maquet, personal fees from Xenios, personal fees from Bayer, non‑financial support from Speaker of the German register of ICUs, grants from the German Ministry of Research and Education, during the conduct of the study. All other authors (SB, FZ, FDS, SuB, MB, CA, and TB) declare no conflict of interest.

Brain lesions in language-related cortical areas remain a challenge in the clinical routine. In recent years, the resting-state fMRI (RS-fMRI) was shown to be a feasible method for preoperative language assessment. The aim of this study was to examine whether language-related resting-state components, which have been obtained using a data-driven independent-component-based identification algorithm, can be supportive in determining language dominance in the left or right hemisphere. Twenty patients suffering from brain lesions close to supposed language-relevant cortical areas were included. RS-fMRI and task-based (TB-fMRI) were performed for the purpose of preoperative language assessment. TB-fMRI included a verb generation task with an appropriate control condition (a syllable switching task) to decompose language-critical and language-supportive processes. Subsequently, the best fitting ICA component for the resting-state language network (RSLN) referential to general linear models (GLMs) of the TB-fMRI (including models with and without linguistic control conditions) was identified using an algorithm based on the Dice index. Thereby, the RSLNs associated with GLMs using a linguistic control condition led to significantly higher laterality indices than GLM baseline contrasts. LIs derived from GLM contrasts with and without control conditions alone did not differ significantly. In general, the results suggest that determining language dominance in the human brain is feasible both with TB-fMRI and RS-fMRI, and in particular, the combination of both approaches yields a higher specificity in preoperative language assessment. Moreover, we can conclude that the choice of the language mapping paradigm is crucial for the mentioned benefits.

Functional magnetic resonance imaging (fMRI) is a valuable tool in the clinical routine of neurosurgery when planning surgical interventions and assessing the risk of postoperative functional deficits. Here, we examined how the presence of a brain tumor or lesion in the area of the occipital lobe affects the results of fMRI retinotopic mapping. fMRI data were evaluated on a retrospectively selected sample of 12 patients with occipital brain tumors, 7 patients with brain lesions and 19 control subjects. Analyses of the cortical activation, percent signal change, cluster size of the activated voxels and functional connectivity were carried out using Statistical Parametric Mapping (SPM12) and the CONN and Marsbar toolboxes. We found similar but reduced patterns of cortical activation and functional connectivity between the two patient groups compared to a healthy control group. Here, we found that retinotopic organization was well-preserved in the patients and was comparable to that of the age-matched controls. The results also showed that, compared to the tumor patients, the lesion patients showed higher percent signal changes but lower values in the cluster sizes of the activated voxels in the calcarine fissure region. Our results suggest that the lesion patients exhibited results that were more similar to those of the control subjects in terms of the BOLD signal, whereas the extent of the activation was comparable to that of the tumor patients.

(1) Background-Mapping language using direct cortical stimulation (DCS) during an awake craniotomy is difficult without using more than one language paradigm that particularly follows the demand of DCS by not exceeding the assessment time of 4 s to prevent intraoperative complications. We designed an intraoperative language paradigm by combining classical picture naming and verb generation, which safely engaged highly relevant language functions. (2) Methods-An evaluation study investigated whether a single trial of the language task could be performed in less than 4 s in 30 healthy subjects and whether the suggested language paradigm sufficiently pictured the cortical language network using functional magnetic resonance imaging (fMRI) in 12 healthy subjects. In a feasibility study, 24 brain tumor patients conducted the language task during an awake craniotomy. The patients' neuropsychological outcomes were monitored before and after surgery. (3) Results-The fMRI results in healthy subjects showed activations in a language-associated network around the (left) sylvian fissure. Single language trials could be performed within 4 s. Intraoperatively, all tumor patients showed DCS-induced language errors while conducting the novel language task. Postoperatively, mild neuropsychological impairments appeared compared to the presurgical assessment. (4) Conclusions-These data support the use of a novel language paradigm that safely monitors highly relevant language functions intraoperatively, which can consequently minimize negative postoperative neuropsychological outcomes.

Purpose: Functional MRI is not routinely used for neurosurgical planning despite potential important advantages, due to difficulty of determining quality. We introduce a novel method for objective evaluation of fMRI scan quality, based on activation maps. A template matching analysis (TMA) is presented and tested on data from two clinical fMRI protocols, performed by healthy controls in seven clinical centers. Preliminary clinical utility is tested with data from low-grade glioma patients., Methods: Data were collected from 42 healthy subjects from seven centers, with standardized finger tapping (FT) and verb generation (VG) tasks. Copies of these "typical" data were deliberately analyzed incorrectly to assess feasibility of identifying them as "atypical." Analyses of the VG task administered to 32 tumor patients assessed sensitivity of the TMA method to anatomical abnormalities., Results: TMA identified all atypical activity maps for both tasks, at the cost of incorrectly classifying 3.6 (VG)-6.5% (FT) of typical maps as atypical. For patients, the average TMA was significantly higher than atypical healthy scans, despite localized anatomical abnormalities caused by a tumor., Conclusion: This study supports feasibility of TMA for objective identification of atypical activation patterns for motor and verb generation fMRI protocols. TMA can facilitate the use and evaluation of clinical fMRI in hospital settings that have limited access to fMRI experts. In a clinical setting, this method could be applied to automatically flag fMRI scans showing atypical activation patterns for further investigation to determine whether atypicality is caused by poor scan data quality or abnormal functional topography.

Background: Following spinal cord injury (SCI), the routine use of magnetic resonance imaging (MRI) resulted in an incremental diagnosis of posttraumatic syringomyelia (PTS). However, facing four decades of preferred surgical treatment of PTS, no clear consensus on the recommended treatment exists. We review the literature on PTS regarding therapeutic strategies, outcomes, and complications., Methods: We performed a systematic bibliographic search on ("spinal cord injuries" [Mesh] AND "syringomyelia" [Mesh]). English language literature published between 1980 and 2020 was gathered, and case reports and articles examining syrinx due to other causes were excluded. The type of study, interval injury to symptoms, severity and level of injury, therapeutic procedure, duration of follow-up, complications, and outcome were recorded., Results: Forty-three observational studies including 1803 individuals met the eligibility criteria. The time interval from SCI to the diagnosis of PTS varied between 42 and 264 months. Eighty-nine percent of patients were treated surgically (n = 1605) with a complication rate of 26%. Symptoms improved in 43% of patients postoperatively and in 2% treated conservatively. Stable disease was documented in 50% of patients postoperatively and in 88% treated conservatively. The percentage of deterioration was similar (surgery 16%, 0.8% dead; conservative 10%). Detailed analysis of surgical outcome with regard to symptoms revealed that pain, motor, and sensory function could be improved in 43 to 55% of patients while motor function deteriorated in around 25%. The preferred methods of surgery were arachnoid lysis (48%) and syrinx drainage (31%)., Conclusion: Even diagnosing PTS early in its evolution with MRI, to date, no satisfactory standard treatment exists, and the present literature review shows similar outcomes, regardless of the treatment modality. Therefore, PTS remains a neurosurgical challenge. Additional research is required using appropriate study designs for improving treatment options.

Background: Significant long-term reduction in health-related quality of life (HRQoL) is often observed in survivors of the acute respiratory distress syndrome (ARDS), and return to work (RtW) is limited. There is a paucity of data regarding the relationship between the quality of care (QoC) in the intensive care unit (ICU) and both HRQoL and RtW in ARDS survivors. Therefore, the aim of our study was to investigate associations between indicators of QoC and HRQoL and RtW in a cohort of survivors of ARDS., Methods: To determine the influence of QoC on HRQoL and RtW 1 year after ICU-discharge, ARDS patients were recruited into a prospective multi-centre patient cohort study and followed up regularly after discharge. Patients were asked to complete self-report questionnaires on HRQoL (Short Form 12 physical component scale (PCS) and mental component scale (MCS)) and RtW. Indicators of QoC pertaining to volume, structural and process quality, and general characteristics were recorded on ICU level. Associations between QoC indicators and HrQoL and RtW were investigated by multivariable linear and Cox regression modelling, respectively. B values and hazard ratios (HRs) are reported with corresponding 95% confidence intervals (CIs)., Results: 877 (of initially 1225 enrolled) people with ARDS formed the DACAPO survivor cohort, 396 were finally followed up to 1 year after discharge. The twelve-month survivors were characterized by a reduced HRQoL with a greater impairment in the physical component (Md 41.2 IQR [34-52]) compared to the mental component (Md 47.3 IQR [33-57]). Overall, 50% of the patients returned to work. The proportion of ventilated ICU patients showed significant negative associations with both 12 months PCS (B = - 11.22, CI -20.71; - 1,74) and RtW (HR = 0,18, CI 0,04;0,80). All other QoC indicators were not significantly related to outcome., Conclusions: Associations between ICU QoC and long-term HrQoL and RtW were weak and largely non-significant. Residual confounding by case mix, treatment variables before or during ICU stay and variables pertaining to the post intensive care period (e.g. rehabilitation) cannot be ruled out., Trial Registration: Clinicaltrials.govNCT02637011. (December 22, 2015, retrospectively registered).

Background: Acute respiratory distress syndrome (ARDS) is a life-threatening condition that often requires prolonged mechanical ventilation. Tracheostomy is a common procedure with some risks, on the other hand with potential advantages over orotracheal intubation in critically ill patients. This study investigated the association of tracheostomy with health-related quality of life (HRQoL), symptoms of psychiatric disorders and return-to-work of ARDS survivors., Methods: Data were collected in the context of the prospective observational German-wide DACAPO study. Clinical and demographic patient data and treatment characteristics were obtained from the participating intensive care units (ICU). HRQoL and return-to-work were assessed using patient-reported questionnaires 3, 6 and 12 months after ICU discharge. HRQoL was measured with the Physical and Mental Component Scale of the Short-Form 12 Questionnaire (PCS-12, MCS-12). The prevalence of psychiatric symptoms (depression and post-traumatic stress disorder [PTSD]) was assessed using the Patient Health Questionnaire-9 and the Post-Traumatic Stress Syndrome-14. Physician-diagnosed anxiety and obsessive-compulsive disorder were recorded by patient self-report in the follow-up questionnaires. The associations of tracheostomy with HRQoL, psychiatric symptoms and return-to-work after 12 months were investigated by means of multivariable linear and logistic regression models., Results: Primary 877 ARDS patients (mean ± standard deviation: 54 ± 16 years, 68% male) survived and were discharged from ICU. Out of these patients, 478 (54.5%) were tracheotomised during ICU treatment. After 12 months, patient-reported outcomes could be analysed of 388 (44.2%) respondents, 205 with tracheostomy and 183 without. One year after ICU discharge, tracheostomy showed no significant association with physical or mental health-related quality of life (PCS-12: - 0.73 [- 3.96, 2.51]; MCS-12: - 0.71 [- 4.92, 3.49]), symptoms of psychiatric disorders (depression: 0.10 [- 1.43, 1.64]; PTSD: 3.31 [- 1.81, 8.43]; anxiety: 1.26 [0.41, 3.86]; obsessive-compulsive disorder: 0.59 [0.05, 6.68]) or return-to-work (0.71 [0.31, 1.64]) in the multivariable analysis (OR [95%-CI])., Conclusions: Up to 1 year after ICU discharge, neither HRQoL nor symptoms of psychiatric disorders nor return-to-work was affected by tracheostomy. Trial registration NCT02637011 (ClinicalTrials.gov, Registered 15 December 2015, retrospectively registered).

Background: Initial treatment (ventilator settings, rescue therapy, supportive measures), and prevention of critical events improve survival in ARDS patients, but little data exists on its effect on health-related quality of life (HRQOL) and return to work (RtW) in survivors. We analyzed the association of the intensity of treatment at ARDS onset and the incidence of critical events on HRQOL and RtW a year after ICU discharge. Methods: In a prospective multi-centre cohort study, the intensity of treatment and the incidence of critical events were determined at 61 ICUs in Germany. At 3, 6, and 12 months, 396 survivors reported their HRQOL (Short-Form 12) and RtW. The parameters of the intensity of acute management (lung protective ventilation, prone position, hemodynamic stabilization, neuromuscular blocking agents), and critical events (hypoxemia, hypoglycemia, hypotension) were associated with HRQOL and RtW. Results: Patients ventilated at ARDS onset with a low tidal volume (VT≤7 ml/kg) had higher arterial carbon dioxide levels (PaCO 2 =57.5±17 mmHg) compared to patients ventilated with VT>7ml/kg (45.7±12, p=0.001). In a multivariate adjusted dichotomized analysis, a better mental 3-month SF-12 was observed in the higher VT-group (mean 43.1±12) compared to the lower VT-group (39.5±9, p=0.042), while a dichotomized analysis for driving pressures (≤14 mbar vs >14 mbar) did not show any difference neither in PaCO 2 levels nor in HRQOL parameters. A decrease in the mental (6-month: 40.0±11 vs 44.8±13, p=0.038) and physical SF-12 (12-month: 38.3±11 vs 43.0±13, p=0.015) was reported from patients with hypoglycemia (blood glucose <70 mg/dl) compared to those without hypoglycemic episodes. More frequent vasopressor use with mean arterial pressure ≥65 mmHg was associated with an impaired physical SF-12 (6-month: 38.8±10) compared to less vasopressor use (43.0±11, p=0.019). Conclusions: In acute management of ARDS, a lower VT strategy associated with hypercapnia, as well as the frequent usage of catecholamines and the management of blood glucose may influence short-term HRQOL of survivors. The awareness of these findings is of clinical importance for the acute and post-ICU care., Competing Interests: This study is part of the DACAPO study which was funded by a research grant from the German Federal Ministry of Education and Research (01GY1340). Grant holders were TB (University Hospital Regensburg, principal investigator) and CA (University of Regensburg, co-principal investigator). SuB, FDS, MB and SeB were funded by this grant for parts of or the entire study period. All other authors received payments from the grant to support patient recruitment. TB, CK, MQ, SK, CP, SvB, BE, TK, CAr, PM, and SWC are members of the German ARDS Network. TB: received honoraria for lectures from Xenios, Germany. MQ: received honoraria for lectures from Maquet and Xenios, Germany. All other authors declare: no relationships/conditions/circumstances that present a potential conflict of interest., (Copyright © 2020 Bein et al.)

Background: For many survivors of acute respiratory distress syndrome (ARDS), the process from discharge from intensive care unit (ICU) to recovery is long and difficult. However, healthcare use after discharge from ICU has received only little attention by research. This study sets out to investigate the extent of ambulatory and stationary healthcare use among survivors of ARDS in Germany (multicenter DACAPO cohort) and to analyze predictors of stationary healthcare use., Results: A total of 396 survivors of ARDS provided data at 1 year after discharge from ICU. Fifty percent of 1-year survivors were hospitalized for 48 days or longer after discharge from ICU, with 10% spending more than six out of 12 months in stationary care. The duration of hospitalization increased significantly by the length of the initial ICU stay. All participants reported at least one outpatient visit (including visits to general practitioners), and 50% contacted four or more different medical specialties within the first year after discharge from ICU., Conclusions: For most of the patients, the first year after ARDS is characterized by an extensive amount of healthcare utilization, especially with regard to stationary health care. These findings shed light on the substantial morbidity of patients after ARDS and contribute to a better understanding of the situation of patients following discharge from ICU.

Despite progress in surgery and radiochemotherapy, the prognosis of glioblastoma (GB) remains poor. GB cells exhibit a preference for hypoxia to maintain their tumor-forming capacity. Treatment strategies utilizing oxygen (O 2 ) or ozone (O3) and generating reactive oxygen species induce cell growth inhibition and apoptosis. The anti-tumorigenic properties of O2-O3 are accompanied by a key role in regulating immunogenicity. The present study reported a case series of an intra-tumoral O2-O3 application in recurrent GB. Following surgery in combination with standard radiochemotherapy, O2-O3 (5 ml at 40 µg/ml) was applied every four weeks into the tumor vicinity. The patients received a median of 27 (range, 3-44) O2-O3 applications. In addition, a systematic literature search was performed in order to evaluate the role of O3 in the treatment of malignancies. The median overall survival rate was 40 (range, 16-53) months. The median survival rate following the first recurrence or the initiation of the O2-O3 treatment, respectively, was 34 (range, 12-53) months. In one patient, a local infection and in another, hemorrhage occurred, necessitating in both the temporary removal of the reservoir. The data from the present study support the potential benefit of an intra-tumoral O2-O3 application in recurrent GB. The scientific literature revealed by the bibliographic search suggests that O3 may be considered a viable adjuvant therapy in oncological patients. The present study may serve as a starting point for further observational and clinical studies elucidating the cellular and systemic effects of O2 and/or O3 and demonstrating their efficacy and safety in larger patient samples.