Severe CSF immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapy.

Cryptococcal meningitis (CM) is a severe fungal disease in immunocompromised patients affecting the central nervous system (CNS). Host response and immunological alterations in the cerebrospinal fluid (CSF) after invasion of Cryptococcus neoformans to the central nervous system have been investigated before but rigorous and comprehensive studies examining cellular changes in the CSF of patients with cryptococccal meningitis are still rare. We retrospectively collected CSF analysis and flow cytometry data of CSF and blood in patients with CM (n = 7) and compared them to HIV positive patients without meningitis (n = 13) and HIV negative healthy controls (n = 7). Within the group of patients with CM we compared those with HIV infection (n = 3) or other immunocompromised conditions (n = 4). Flow cytometry analysis revealed an elevation of natural killer cells and natural killer T cells in the CSF and blood of HIV negative patients with CM, pointing to innate immune activation in early stages after fungal invasion. HIV positive patients with CM exhibited stronger blood-CSF-barrier disruption. Follow-up CSF analysis over up to 150 days showed heterogeneous cellular courses in CM patients with slow normalization of CSF after induction of antifungal therapy.

Role and relevance of dentists in a multiprofessional palliative care team: results of a cross-sectional survey study.

PURPOSE: Despite the multiprofessional concept surrounding palliative care patients (PCPs) and their high prevalence of oral issues, licensed dentists (LDs) are often not included in their treatment team. This study aimed to examine the current state of cooperation and to determine whether and how LDs should be included in the care for PCPs. METHODS: This single-centre cross-sectional study was conducted at the University Hospital Muenster, Germany. We surveyed three participant groups: PCPs, LDs, and healthcare professionals (HCPs). Questionnaires were tailored for each group, with some questions common for comparison. RESULTS: The study encompassed the results of 48 questionnaires from LDs, 50 from PCPs along with 50 from HCPs. Consensus was reached among all parties (LDs: 73% (n = 35/48); HCPs: 94%, n = 47/50; PCPs: 60%, n = 30/50) that involving LDs in the treatment concept is favourable. On the other hand, a significant discrepancy emerged in the perception of the dental treatment effort required by PCPs. While LDs (81%; n = 39/48) and HCPs (64%; n = 32/50) were convinced of increased effort, PCPs (34%; n = 17/50) largely did not share this perspective. To enhance patient care and formulate appropriate treatment plans, LDs consider both training (58%; n = 28/48) and guidebooks (71%; n = 34/48) to be valuable and would attend or use such resources. CONCLUSION: This study sheds light on the current gaps in including LDs in palliative care teams and emphasizes the importance of multidisciplinary collaboration to address oral health needs effectively. Development of continuing education options and collaborative models between LDs and HCPs needs to be further expanded in future.

Unused potential of lipid-lowering therapy in very high-risk patients with atherosclerotic cardiovascular disease. A retrospective data analysis.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is the most common cause of death in Europe. Although the 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines for the management of dyslipidaemias claim a target low-density lipoprotein cholesterol (LDL-C) value of <55 mg/dL for very high-risk patients by use of lipid-lowering therapy (LLT) and lifestyle adaptations, the target level achievement is not satisfactory. We examined LLT use in ASCVD patients exceeding LDL-C target levels at admission and its adaptations at discharge. METHODS AND RESULTS: Between January 2017 and February 2020, 1091 patients with LDL-C >100 mg/dL and ASCVD defined as diagnosis of angina pectoris (AP, n = 179), acute myocardial infarction (AMI, n = 317), chronic ischemic heart disease (CHD, n = 195), or peripheral artery disease (PAD, n = 400) were extracted from hospital records. LLT use on admission and discharge as well as recommendations on lifestyle and nutrition were analysed. On admission, 51% of the patients were not taking LLT. At discharge, 91% were prescribed statins and 87% were advised on lifestyle adaptation and/or pharmacological treatment. High-intensity statin use at discharge was present in 63% of the AP-group, 92% of the AMI-group, 62% of the CHD-group and 71% of the PAD-group. Ezetimibe was present in 16% and proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) in 1%. However, of those on high-intensity statin, 25% remained on insufficient statin dosage. CONCLUSION: Switch to high-intensity statins and use of ezetimibe and PCSK9i was low in chronic ASCVD patients. Even though statin intake was high in high-risk patients, target levels were still not reached.

Telemedicine Plus Standard Care Versus Standard Care Only in Specialized Outpatient Palliative Care: A Randomized Controlled Noninferiority Trial.

Background: Patients suffering from incurable diseases are more likely to die in the hospital than at home. Specialized outpatient palliative care (PC) may be able to counteract this tendency. Similarly, potential benefits of telemedicine in health care were scientifically reported. The aim of this research was to compare patients receiving specialized outpatient PC plus telemedicine with those receiving standard specialized outpatient PC only. In this study, telemedicine is assumed to decrease the number of home visits and therefore should not be considered a mere add-on. Methods: This is a randomized controlled noninferiority trial. Recruitment lasted between January 2020 and October 2021. Quality of care was evaluated using the Integrated Palliative Care Outcome Scale (IPOS) at day 0, 7, and 14 after randomization. Change from day 0 to 7 was defined as the primary outcome (noninferiority margin = 4 points). This study was conducted in an urban setting in collaboration with a university hospital and a local specialized outpatient PC service. Results: A total of 196 patients were screened with 34 patients included (18 telemedicine/16 standard care). The mean change in the total score of the IPOS from day 0 to 7 amounted to -1.8 ± 3.9 (telemedicine) versus 1.2 ± 5.7 (standard care). The telemedicine group was statistically not relevantly inferior to the standard care group (t-test for noninferiority, p = 0.005). Conclusions: Although, due to COVID-19, the sample size remained rather small, our findings indicate that telemedical approaches offer a promising and equally effective option to provide specialized outpatient PC. Clinical Trial Registration Number: NCT06054048.

Supporting the differential diagnosis of connective tissue diseases with neurological involvement by blood and cerebrospinal fluid flow cytometry.

OBJECTIVE: Neurological manifestations of autoimmune connective tissue diseases (CTD) are poorly understood and difficult to diagnose. We here aimed to address this shortcoming by studying immune cell compositions in CTD patients with and without neurological manifestation. METHODS: Using flow cytometry, we retrospectively investigated paired cerebrospinal fluid (CSF) and blood samples of 28 CTD patients without neurological manifestation, 38 CTD patients with neurological manifestation (N-CTD), 38 non-inflammatory controls, and 38 multiple sclerosis (MS) patients, a paradigmatic primary neuroinflammatory disease. RESULTS: We detected an expansion of plasma cells in the blood of both N-CTD and CTD compared to non-inflammatory controls and MS. Blood plasma cells alone distinguished the clinically similar entities N-CTD and MS with high discriminatory performance (AUC: 0.81). Classical blood monocytes indicated higher disease activity in systemic lupus erythematosus (SLE) patients. Surprisingly, immune cells in the CSF did not differ significantly between N-CTD and CTD, while CD4+ T cells and the CD4+/CD8+ ratio were elevated in the blood of N-CTD compared to CTD. Several B cell-associated parameters partially overlapped in the CSF in MS and N-CTD. We built a machine learning model that distinguished N-CTD from MS with high discriminatory power using either blood or CSF. CONCLUSION: We here find that blood flow cytometry alone surprisingly suffices to distinguish CTD with neurological manifestations from clinically similar entities, suggesting that a rapid blood test could support clinicians in the differential diagnosis of N-CTD.

Determinants of cognition in autoimmune limbic encephalitis-A retrospective cohort study.

Autoimmune limbic encephalitis (ALE) is the most common type of autoimmune encephalitis (AIE). Subacute memory disturbance, temporal lobe seizures, and psychiatric symptoms are clinical hallmarks of the disease. However, little is known on the factors contributing to cognitive functioning in ALE. Hence, we here investigate major determinants of cognitive functioning in ALE. In a retrospective analysis of 102 patients with ALE, we first compared verbal learning capacity, nonverbal learning capacity, and attentional and executive functioning by absence or presence of different types of neural autoantibodies (AABs). Subsequently we established three linear regression models including 63, 38, and 61 patients, respectively to investigate how cognitive functioning in these domains may depend on common markers of ALE such as intrathecal inflammation, blood-cerebrospinal fluid (CSF)-barrier function, mesiotemporal epileptiform discharges and slowing, determined by electroencephalography (EEG) and structural mesiotemporal changes, measured with magnetic resonance imaging (MRI). We also accounted for possible effects of cancer- and immunotherapy and other centrally effective medication. There was no effect of AAB status on cognitive functioning. Although the regression models could not predict verbal and nonverbal learning capacity, structural mesiotemporal neural network alterations on T2-/fluid attenuated inversion recovery (FLAIR)-signal-weighted MRI and mesiotemporal epileptiform discharges or slowing on EEG exerted a significant impact on memory functions. In contrast, the regression model significantly predicted attentional and executive functioning with CSF white blood cell count and centrally effective medication being significant determinants. In this cohort, cognitive functioning in ALE does not depend on the AAB status. Common markers of ALE cannot predict memory functioning that only partially depends on structural and functional alterations of mesiotemporal neural networks. Common markers of ALE significantly predict attentional and executive functioning that is significantly related to centrally effective medication and CSF white blood cell count, which may point toward inflammation affecting brain regions beyond the limbic system.

Blood and cerebrospinal fluid immune cell profiles in patients with temporal lobe epilepsy of different etiologies.

Inflammation plays a role in the pathogenesis of immune-mediated epilepsy, but also in epilepsy of other etiology such as hippocampal sclerosis. This study aimed to characterize immune cell signatures in the peripheral blood (PB) and cerebrospinal fluid (CSF) in temporal lobe epilepsy (TLE) of different etiologies. We retrospectively evaluated CSF routine parameters and immune cell profiles using flow cytometry in a cohort of 51 patients and 45 age-matched controls with functional disorders. Groups were comprised of patients with nonlesional TLE (n = 26), TLE due to hippocampal sclerosis (n = 14), or limbic encephalitis with antibodies against the 65-kDa isoform of glutamic acid decarboxylase (GAD65-LE; n = 11). TLE patients showed increased proportions of human leukocyte antigen-DR isotype (HLA-DR)-expressing CD4+ T lymphocytes in the CSF. Furthermore, they were characterized by a shift in monocyte subsets toward immature CD14low CD16+ cells in the PB and blood/CSF-barrier dysfunction. Whereas TLE patients in general showed similar immune cell profiles, patients with GAD65-LE differed from other TLE patients by increased proportions of HLA-DR-expressing CD8+ T lymphocytes and type 2/3 oligoclonal bands. These findings point to a role of innate and adaptive immunity in TLE. CSF parameters may help to discriminate epilepsy patients from controls and different forms of TLE from each other.

Evaluation of Respiratory Muscle Strength and Diaphragm Ultrasound: Normative Values, Theoretical Considerations, and Practical Recommendations.

BACKGROUND: Reference values derived from existing diaphragm ultrasound protocols are inconsistent, and the association between sonographic measures of diaphragm function and volitional tests of respiratory muscle strength is still ambiguous. OBJECTIVE: To propose a standardized and comprehensive protocol for diaphragm ultrasound in order to determine lower limits of normal (LLN) for both diaphragm excursion and thickness in healthy subjects and to explore the association between volitional tests of respiratory muscle strength and diaphragm ultrasound parameters. METHODS: Seventy healthy adult subjects (25 men, 45 women; age 34 ± 13 years) underwent spirometric lung function testing, determination of maximal inspiratory and expiratory pressure along with ultrasound evaluation of diaphragm excursion and thickness during tidal breathing, deep breathing, and maximum voluntary sniff. Excursion data were collected for amplitude and velocity of diaphragm displacement. Diaphragm thickness was measured in the zone of apposition at total lung capacity (TLC) and functional residual capacity (FRC). All participants underwent invasive measurement of transdiaphragmatic pressure (Pdi) during different voluntary breathing maneuvers. RESULTS: Ultrasound data were successfully obtained in all participants (procedure duration 12 ± 3 min). LLNs (defined as the 5th percentile) for diaphragm excursion were as follows: (a) during tidal breathing: 1.2 cm (males; M) and 1.2 cm (females; F) for amplitude, and 0.8 cm/s (M) and 0.8 cm/s (F) for velocity, (b) during maximum voluntary sniff: 2.0 cm (M) and 1.5 cm (F) for amplitude, and 6.7 (M) cm/s and 5.2 cm/s (F) for velocity, and (c) at TLC: 7.9 cm (M) and 6.4 cm (F) for amplitude. LLN for diaphragm thickness was 0.17 cm (M) and 0.15 cm (F) at FRC, and 0.46 cm (M) and 0.35 cm (F) at TLC. Values for males were consistently higher than for females, independent of age. LLN for diaphragmatic thickening ratio was 2.2 with no difference between genders. LLN for invasively measured Pdi during different breathing maneuvers are presented. Voluntary Pdi showed only weak correlation with both diaphragm excursion velocity and amplitude during forced inspiration. CONCLUSIONS: Diaphragm ultrasound is an easy-to-perform and reproducible diagnostic tool for noninvasive assessment of diaphragm excursion and thickness. It supplements but does not replace respiratory muscle strength testing.

Respiratory Muscle and Lung Function in Lung Allograft Recipients: Association with Exercise Intolerance.

BACKGROUND: In lung transplant recipients (LTRs), restrictive ventilation disorder may be present due to respiratory muscle dysfunction that may reduce exercise capacity. This might be mediated by pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). OBJECTIVE: We investigated lung respiratory muscle function as well as circulating pro-inflammatory cytokines and exercise capacity in LTRs. METHODS: Fifteen LTRs (6 female, age 56 ± 14 years, 63 ± 45 months post-transplantation) and 15 healthy controls matched for age, sex, and body mass index underwent spirometry, measurement of mouth occlusion pressures, diaphragm ultrasound, and recording of twitch transdiaphragmatic (twPdi) and gastric pressures (twPgas) following magnetic stimulation of the phrenic nerves and the lower thoracic nerve roots. Exercise capacity was quantified using the 6-min walking distance (6MWD). Plasma IL-6 and TNF-α were measured using enzyme-linked immunosorbent assays. RESULTS: Compared with controls, patients had lower values for forced vital capacity (FVC; 81 ± 30 vs.109 ± 18% predicted, p = 0.01), maximum expiratory pressure (100 ± 21 vs.127 ± 17 cm H2O, p = 0.04), diaphragm thickening ratio (2.2 ± 0.4 vs. 3.0 ± 1.1, p = 0.01), and twPdi (10.4 ± 3.5 vs. 17.6 ± 6.7 cm H2O, p = 0.01). In LTRs, elevation of TNF-α was related to lung function (13 ± 3 vs. 11 ± 2 pg/mL in patients with FVC ≤80 vs. >80% predicted; p < 0.05), and lung function (forced expiratory volume after 1 s) was closely associated with diaphragm thickening ratio (r = 0.81; p < 0.01) and 6MWD (r = 0.63; p = 0.02). CONCLUSION: There is marked restrictive ventilation disorder and respiratory muscle weakness in LTRs, especially inspiratory muscle weakness with diaphragm dysfunction. Lung function impairment relates to elevated levels of circulating TNF-α and diaphragm dysfunction and is associated with exercise intolerance.

Correction to: Validity of transit time-based blood pressure measurements in patients with and without heart failure or pulmonary arterial hypertension across different breathing maneuvers.

After the publication of the original manuscript we found that the calculation of the supplemental data regarding the capacity of PTT-based blood pressure (BP) recordings to detect changes in systolic and diastolic BP in different cohorts of patients was incorrect. These errors occured when data were transformed from MS Excel to Sigma-Plot tables. In this correction, the affected data and the respective figures were now revised.

Validity of transit time-based blood pressure measurements in patients with and without heart failure or pulmonary arterial hypertension across different breathing maneuvers.

PURPOSE: Pulse transit time (PTT) derived by ECG and plethysmographic signal can be a promising alternative to invasive or oscillometry-based blood pressure (BP) monitoring in sleep laboratories because it does not cause arousals from sleep. Therefore, this study assessed the validity of PTT for BP monitoring under sleep laboratory-like conditions. METHODS: Ten volunteers (55.8 ± 19.6 years), 12 patients with heart failure with reduced ejection fraction (HFrEF; 67.3 ± 8.6 years), and 14 patients with Nizza class I pulmonary arterial hypertension (PAH; 59.5 ± 13.4 years) performed different breathing patterns to simulate nocturnal sleep-disordered breathing (SDB). BP was measured at least every 15 min over 1 h using oscillometry (Task Force Monitor™) and PTT (SOMNOscreen™) devices in free breathing conditions and during SDB simulation (alternating phases of hyperventilation and apneas). RESULTS: One hundred forty-two points of measurements were collected. No difference was found in both mean systolic BP (SBP) and diastolic BP (DBP) between oscillometric PTT-based BP measurements in the whole population and throughout the whole recording (SBP 111.3 ± 15.1 mmHg versus 110.0 ± 14.7 mmHg, p = 0.051; DBP 69.9 ± 12.2 versus 69.9 ± 14.2 mmHg, p = 0.701). Likewise, no significant difference in SBP and DBP was found between the two methods in the subgroups of healthy subjects, HFrEF patients and PAH patients, both in free breathing conditions (p > 0.05) and during SDB simulation (p > 0.05). CONCLUSIONS: When monitoring BP in healthy subjects, and in patients with HFrEF or PAH, PTT provides a BP estimation comparable with oscillometric measurement, though slightly inaccurate, both in the condition of regular and unstable breathing.

Respiratory muscle weakness in facioscapulohumeral muscular dystrophy.

INTRODUCTION: The purpose of this study was to comprehensively evaluate respiratory muscle function in adults with facioscapulohumeral muscular dystrophy (FSHD). METHODS: Fourteen patients with FSHD (9 men, 53 ± 16 years of age) and 14 matched controls underwent spirometry, diaphragm ultrasound, and measurement of twitch gastric and transdiaphragmatic pressures (twPgas and twPdi; n = 10) after magnetic stimulation of the lower thoracic nerve roots and the phrenic nerves. The latter was combined with recording of diaphragm compound muscle action potentials (CMAPs; n = 14). RESULTS: The following parameters were significantly lower in patients vs controls: forced vital capacity (FVC); maximum inspiratory and expiratory pressure; peak cough flow; diaphragm excursion amplitude; and thickening ratio on ultrasound, twPdi (11 ± 5 vs 20 ± 6 cmH2 O) and twPgas (7 ± 3 vs 25 ± 20 cmH2 O). Diaphragm CMAP showed no group differences. FVC correlated inversely with the clinical severity scale score (r = -0.63, P = .02). DISCUSSION: In FSHD, respiratory muscle weakness involves both the diaphragm and the expiratory abdominal muscles.

Phrenic nerve involvement and respiratory muscle weakness in patients with Charcot-Marie-Tooth disease 1A.

Diaphragm weakness in Charcot-Marie-Tooth disease 1A (CMT1A) is usually associated with severe disease manifestation. This study comprehensively investigated phrenic nerve conductivity, inspiratory and expiratory muscle function in ambulatory CMT1A patients. Nineteen adults with CMT1A (13 females, 47 ± 12 years) underwent spiromanometry, diaphragm ultrasound, and magnetic stimulation of the phrenic nerves and the lower thoracic nerve roots, with recording of diaphragm compound muscle action potentials (dCMAP, n = 15), transdiaphragmatic and gastric pressures (twPdi and twPgas, n = 12). Diaphragm motor evoked potentials (dMEP, n = 15) were recorded following cortical magnetic stimulation. Patients had not been selected for respiratory complaints. Disease severity was assessed using the CMT Neuropathy Scale version 2 (CMT-NSv2). Healthy control subjects were matched for age, sex, and body mass index. The following parameters were significantly lower in CMT1A patients than in controls (all P < .05): forced vital capacity (91 ± 16 vs 110 ± 15% predicted), maximum inspiratory pressure (68 ± 22 vs 88 ± 29 cmH2 O), maximum expiratory pressure (91 ± 23 vs 123 ± 24 cmH2 O), and peak cough flow (377 ± 135 vs 492 ± 130 L/min). In CMT1A patients, dMEP and dCMAP were delayed. Patients vs controls showed lower diaphragm excursion (5 ± 2 vs 8 ± 2 cm), diaphragm thickening ratio (DTR, 1.9 [1.6-2.2] vs 2.5 [2.1-3.1]), and twPdi (8 ± 6 vs 19 ± 7 cmH2 O; all P < .05). DTR inversely correlated with the CMT-NSv2 score (r = -.59, P = .02). There was no group difference in twPgas following abdominal muscle stimulation. Ambulatory CMT1A patients may show phrenic nerve involvement and reduced respiratory muscle strength. Respiratory muscle weakness can be attributed to diaphragm dysfunction alone. It relates to neurological impairment and likely reflects a disease continuum.

Assessment of Central Drive to the Diaphragm by Twitch Interpolation: Normal Values, Theoretical Considerations, and Future Directions.

BACKGROUND: The twitch interpolation technique is a promising tool for assessing central drive to the diaphragm. It is used to quantify the degree of voluntary diaphragm activation during predefined breathing maneuvers. OBJECTIVES: This study was designed to (a) determine reference values for the level of voluntary activation of the diaphragm using the twitch occlusion technique in healthy adults and (b) explore the association between central drive to the diaphragm and volitional tests of respiratory muscle strength. METHODS: Twenty-seven healthy volunteers aged 26 ± 14 years (18 male) were enrolled. Twitch transdiaphragmatic pressure (Pdi) was determined at relaxed functional residual capacity in response to cervical magnetic stimulation (CMS) of the phrenic nerves. The subjects were then instructed to gradually increase voluntary activation of the diaphragm, and the effects of superimposed magnetic stimuli on voluntary Pdi were assessed. RESULTS: The twitch Pdi amplitude following CMS linearly decreased with increasing inspiratory effort. The resulting diaphragm voluntary activation index (DVAI) during maximal voluntary contraction was 75 ± 15% irrespective of gender or age. Twitch duration, half relaxation time, and area under the curve of superimposed Pdi deflections did not show a linear but an exponential association with increasing voluntary activation of the diaphragm. More than 2/3 of the decrease in the above values was evident after 1/3 of voluntary diaphragm contraction. Forced vital capacity (FVC) was inversely correlated with the DVAI. CONCLUSIONS: Twitch interpolation allows for assessment of central drive to the diaphragm. The maximum DVAI is independent of gender or age, and significantly related to FVC but not to maximum inspiratory pressure or Pdi as direct measures of diaphragm strength.

Noninvasive Prediction of Twitch Transdiaphragmatic Pressure: Insights from Spirometry, Diaphragm Ultrasound, and Phrenic Nerve Stimulation Studies.

BACKGROUND: Twitch transdiaphragmatic pressure (twPdi) following magnetic stimulation (MS) of the phrenic nerves is the gold standard for non-volitional assessment of diaphragm strength. Expiratory muscle function can be investigated using MS of the abdominal muscles and measurement of twitch gastric pressure (twPgas). OBJECTIVES: To investigate whether twitch pressures following MS of the phrenic and lower thoracic nerve roots can be predicted noninvasively by diaphragm ultrasound parameters and volitional tests of respiratory muscle strength. METHODS: Sixty-three healthy subjects underwent standard spirometry, measurement of maximum inspiratory (PImax) and expiratory pressure (PEmax), and diaphragm ultrasound. TwPdi following cervical MS of the phrenic nerve roots and twPgas after lower thoracic MS (twPgas-Thor) were measured using esophageal and gastric balloon catheters inserted transnasally. Using surface electrodes, compound muscle action potentials (CMAP) were simultaneously recorded from the diaphragm or obliquus abdominis muscles, respectively. RESULTS: Forced expiratory flow (FEF25-75) was significantly correlated with twPdi (r = 0.37; p = 0.003) and its components (twPgas and twitch esophageal pressure, twPes). Diaphragm excursion velocity during tidal breathing was correlated to twPes (r = 0.44; p = 0.02). No prediction of twitch pressures was possible from CMAP amplitude, forced vital capacity (FVC), or PImax. TwPgas-Thor was correlated with FEF25-75 (r = 0.46; p = 0.05) and diaphragm thickness at total lung capacity (r = 0.38; p = 0.04) but could not be predicted from CMAP amplitude, FVC, or PEmax. CONCLUSIONS: TwPdi and twPgas-Thor cannot be predicted from volitional measures of respiratory muscle strength, diaphragm and abdominal CMAP, or diaphragm ultrasound. Invasive recording of esophageal and gastric pressures following MS remains indispensable for objective assessment of respiratory muscle strength.

Sleep-related breathing disorders in facioscapulohumeral dystrophy.

PURPOSE: Severe manifestations of facioscapulohumeral dystrophy (FSHD) may be associated with sleep-disordered breathing (SDB), including obstructive sleep apnea (OSA) and nocturnal hypoventilation (NH), but prevalence data are scarce. In patients with respiratory muscle weakness, detection of NH can be facilitated by transcutaneous capnometry, but respective data derived from FSHD patients have not yet been published. METHODS: We collected sleep studies and capnometry recordings from 31 adult patients with genetically confirmed FSHD who were admitted to our sleep laboratory for first-ever evaluation of sleep-related breathing. Indications for admission included non-restorative sleep, morning headache, or excessive daytime sleepiness. In addition, sleep studies were initiated if symptoms or signs of respiratory muscle weakness were present. Thirty-one subjects with insomnia served as controls for comparison of respiratory measures during sleep. RESULTS: In the FSHD group, 17/31 (55%) patients showed OSA and 8 (26%) had NH. NH would have been missed in 7/8 patients if only oximetry criteria of hypoventilation had been applied. Capnography results were correlated with disease severity as reflected by the Clinical Severity Score (CSS). Non-invasive ventilation (NIV) was started in 6 patients with NH and 3 individuals with OSA. Nocturnal continuous positive airway pressure was administered to 2 patients, and positional therapy was sufficient in 4 individuals. In patients initiated on NIV, nocturnal gas exchange already improved in the first night of treatment. CONCLUSIONS: SDB is common in adult patients with FSHD complaining of sleep-related symptoms. It may comprise OSA, NH, and most often, the combination of both. Sleep-related hypercapnia is associated with disease severity. Transcutaneous capnometry is superior to pulse oximetry for detection of NH.

Adverse events in brain tumor surgery: incidence, type, and impact on current quality metrics.

BACKGROUND: The aim of the study was to determine pre-operative factors associated with adverse events occurring within 30 days after neurosurgical tumor treatment in a German center, adjusting for their incidence in order to prospectively compare different centers. METHODS: Adult patients that were hospitalized due to a benign or malignant brain were retrospectively assessed for quality indicators and adverse events. Analyses were performed in order to determine risk factors for adverse events and reasons for readmission and reoperation. RESULTS: A total of 2511 cases were enrolled. The 30 days unplanned readmission rate to the same hospital was 5.7%. The main reason for readmission was tumor progression. Every 10th patient had an unplanned reoperation. The incidence of surgical revisions due to infections was 2.3%. Taking together all monitored adverse events, male patients had a higher risk for any of these complications (OR 1.236, 95%CI 1.025-1.490, p = 0.027). Age, sex, and histological diagnosis were predictors of experiencing any complication. Adjusted by incidence, the increased risk ratios greater than 10.0% were found for male sex, age, metastatic tumor, and hemiplegia for various quality indicators. CONCLUSIONS: We found that most predictors of outcome rates are based on preoperative underlying medical conditions and are not modifiable by the surgeon. Comparing our results to the literature, we conclude that differences in readmission and reoperation rates are strongly influenced by standards in decision making and that comparison of outcome rates between different health-care providers on an international basis is challenging. Each health-care system has to develop own metrics for risk adjustment that require regular reassessment.

Establishing risk-adjusted quality indicators in surgery using administrative data-an example from neurosurgery.

BACKGROUND: The current draft of the German Hospital Structure Law requires remuneration to incorporate quality indicators. For neurosurgery, several quality indicators have been discussed, such as 30-day readmission, reoperation, or mortality rates; the rates of infections; or the length of stay. When comparing neurosurgical departments regarding these indicators, very heterogeneous patient spectrums complicate benchmarking due to the lack of risk adjustment. OBJECTIVE: In this study, we performed an analysis of quality indicators and possible risk adjustment, based only on administrative data. METHODS: All adult patients that were treated as inpatients for a brain or spinal tumour at our neurosurgical department between 2013 and 2017 were assessed for the abovementioned quality indicators. DRG-related data such as relative weight, PCCL (patient clinical complexity level), ICD-10 major diagnosis category, secondary diagnoses, age and sex were obtained. The age-adjusted Charlson Comorbidity Index (CCI) was calculated. Logistic regression analyses were performed in order to correlate quality indicators with administrative data. RESULTS: Overall, 2623 cases were enrolled into the study. Most patients were treated for glioma (n = 1055, 40.2%). The CCI did not correlate with the quality indicators, whereas PCCL showed a positive correlation with 30-day readmission and reoperation, SSI and nosocomial infection rates. CONCLUSION: All previously discussed quality indicators are easily derived from administrative data. Administrative data alone might not be sufficient for adequate risk adjustment as they do not reflect the endogenous risk of the patient and are influenced by certain complications during inpatient stay. Appropriate concepts for risk adjustment should be compiled on the basis of prospectively designed registry studies.

Velocity mapping of the aortic flow at 9.4 T in healthy mice and mice with induced heart failure using time-resolved three-dimensional phase-contrast MRI (4D PC MRI).

OBJECTIVES: In this study, we established and validated a time-resolved three-dimensional phase-contrast magnetic resonance imaging method (4D PC MRI) on a 9.4 T small-animal MRI system. Herein we present the feasibility of 4D PC MRI in terms of qualitative and quantitative flow pattern analysis in mice with transverse aortic constriction (TAC). MATERIALS AND METHODS: 4D PC FLASH images of a flow phantom and mouse heart were acquired at 9.4 T using a four-point phase-encoding scheme. The method was compared with slice-selective PC FLASH and ultrasound using Bland-Altman analysis. Advanced 3D streamlines were visualized utilizing Voreen volume-rendering software. RESULTS: In vitro, 4D PC MRI flow profiles showed the transition between laminar and turbulent flow with increasing velocities. In vivo, 4D PC MRI data of the ascending aorta and the pulmonary artery were confirmed by ultrasound, resulting in linear regressions of R (2) > 0.93. Magnitude- and direction-encoded streamlines differed substantially pre- and post-TAC surgery. CONCLUSIONS: 4D PC MRI is a feasible tool for in vivo velocity measurements on high-field small-animal scanners. Similar to clinical measurement, this method provides a complete spatially and temporally resolved dataset of the murine cardiovascular blood flow and allows for three-dimensional flow pattern analysis.