Real-time quantification of in vivo cerebrospinal fluid velocity using the functional magnetic resonance imaging inflow effect.

In vivo estimation of cerebrospinal fluid (CSF) velocity is crucial for understanding the glymphatic system and its potential role in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Current cardiac or respiratory-gated approaches, such as 4D flow magnetic resonance imaging (MRI), cannot capture CSF movement in real time because of limited temporal resolution and, in addition, deteriorate in accuracy at low fluid velocities. Other techniques like real-time phase-contrast-MRI or time-spatial labeling inversion pulse are not limited by temporal averaging but have limited availability, even in research settings. This study aims to quantify the inflow effect of dynamic CSF motion on functional MRI (fMRI) for in vivo, real-time measurement of CSF flow velocity. We considered linear and nonlinear models of velocity waveforms and empirically fit them to fMRI data from a controlled flow experiment. To assess the utility of this methodology in human data, CSF flow velocities were computed from fMRI data acquired in eight healthy volunteers. Breath-holding regimens were used to amplify CSF flow oscillations. Our experimental flow study revealed that CSF velocity is nonlinearly related to inflow effect-mediated signal increase and well estimated using an extension of a previous nonlinear framework. Using this relationship, we recovered velocity from in vivo fMRI signal, demonstrating the potential of our approach for estimating CSF flow velocity in the human brain. This novel method could serve as an alternative approach to quantifying slow flow velocities in real time, such as CSF flow in the ventricular system, thereby providing valuable insights into the glymphatic system's function and its implications for neurological disorders.

Shape-Sensing Robotic-Assisted Bronchoscopy in the Multiple Pulmonary Nodule Diagnosis during a Single Anesthetic Event.

INTRODUCTION: The widespread use of computed tomography as a screening tool for early lung cancer has increased detection of pulmonary lesions. It is common to encounter patients with more than one peripheral pulmonary nodule (PPN) of uncertain etiology. Shape-sensing robotic-assisted bronchoscopy (ssRAB) emerges as a potential alternative to biopsy multiple PPN, in addition to mediastinal staging in single anesthetic procedure. METHODS: This is a single-center, retrospective review of 22 patients who underwent ssRAB for evaluation of two or more PPN, between November 2021 and April 2023 at Mayo Clinic, FL, USA. RESULTS: A total of 46 PPNs were biopsied in 22 patients. All lesions were ≤2 cm with a median minimum and maximum cross-sectional lesion size of 1.40 cm and 1.05 cm, respectively. Diagnostic yield was 86.9% (n = 40), and target reach was 91.3% (n = 42). Most lesions were in the upper lobes, a solid pattern was found in 78.3% (n = 36), bronchus sign was present in 82.6% of cases (n = 38), 54.4% (n = 25) were malignant nodules, and 32.6% (n = 15) were benign. Fourteen patients had at least one malignant lesion out of two or more nodules sampled, and 10 patients had a malignant diagnosis for all sampled lesions. The complication rate was 9% (n = 2) with one case of bleeding and one of pneumothorax. CONCLUSION: This study is, to our knowledge, the first to assess the use and safety of ssRAB for diagnosis of multiple PPN in a single anesthetic event. This procedure will mainly impact management decisions and subsequently shorten the time from diagnosis to treatment.

Shape-Sensing Robotic-Assisted Bronchoscopy versus Computed Tomography-Guided Transthoracic Biopsy for the Evaluation of Subsolid Pulmonary Nodules.

INTRODUCTION: Lung cancer remains the leading cause of cancer death worldwide. Subsolid nodules (SSN), including ground-glass nodules (GGNs) and part-solid nodules (PSNs), are slow-growing but have a higher risk for malignancy. Therefore, timely diagnosis is imperative. Shape-sensing robotic-assisted bronchoscopy (ssRAB) has emerged as reliable diagnostic procedure, but data on SSN and how ssRAB compares to other diagnostic interventions such as CT-guided transthoracic biopsy (CTTB) are scarce. In this study, we compared diagnostic yield of ssRAB versus CTTB for evaluating SSN. METHODS: A retrospective study of consecutive patients who underwent either ssRAB or CTTB for evaluating GGN and PSN with a solid component less than 6 mm from February 2020 to April 2023 at Mayo Clinic Florida and Rochester. Clinicodemographic information, nodule characteristics, diagnostic yield, and complications were compared between ssRAB and CTTB. RESULTS: A total of 66 nodules from 65 patients were evaluated: 37 PSN and 29 GGN. Median size of PSN solid component was 5 mm (IQR: 4.5, 6). Patients were divided into two groups: 27 in the ssRAB group and 38 in the CTTB group. Diagnostic yield was 85.7% for ssRAB and 89.5% for CTTB (p = 0.646). Sensitivity for malignancy was similar between ssRAB and CTTB (86.4% vs. 88.5%; p = 0.828), with no statistical difference. Complications were more frequent in CTTB with no significant difference (8 vs. 2; p = 0.135). CONCLUSION: Diagnostic yield for SSN was similarly high for ssRAB and CTTB, with ssRAB presenting less complications and allowing mediastinal staging within the same procedure.

Robotic-assisted bronchoscopy versus CT-guided transthoracic biopsy for diagnosis of pulmonary nodules.

BACKGROUND AND OBJECTIVE: Currently, computed tomography-guided transthoracic biopsy (CTTB) is the most accurate diagnostic approach for pulmonary nodules suspected of malignancy. Traditional bronchoscopy has shown suboptimal diagnostic sensitivity, but the emergence of robotic-assisted bronchoscopy (RAB) has the potential to improve diagnostic accuracy, maximize diagnostic yield and complete mediastinal and hilar staging in a single procedure. We aim to assess the efficacy and diagnostic performance of RAB compared to CTTB for diagnosing pulmonary nodules suspected of lung cancer. METHODS: A multicenter retrospective review of consecutive patients who underwent RAB and CTTB for evaluating pulmonary nodules from January 2019 to March 2021 at Mayo Clinic Florida and Mayo Clinic Rochester, United States. Clinical and demographic information, nodule characteristics, outcomes and complications were compared between RAB and CTTB. RESULTS: A total of 225 patients were included: 113 in the RAB group and 112 in the CTTB group. Overall diagnostic yield was 87.6% for RAB and 88.4% for CTTB. For malignant disease, RAB had a sensitivity of 82.1% and a specificity of 100%, CTTB had a sensitivity of 88.5% and a specificity of 100%. Complication rate was significantly higher for CTTB compared to RAB (17% vs. 4.4%; p = 0.002). CONCLUSION: RAB, when available, can be as accurate as CTTB for sampling pulmonary nodules with similar or reduced complications and should be considered as a means for nodule biopsy, particularly when mediastinal staging is also clinically warranted.

Diagnostic Yield of Shape-Sensing Robotic-Assisted Bronchoscopy for Ground-Glass Nodules and Subsolid Nodules with a Solid Component Less than 6 mm.

BACKGROUND: Ground-glass pulmonary nodules (GGNs) are most commonly sampled by percutaneous transthoracic biopsy. Diagnostic yield for ground-glass nodules using robotic-assisted bronchoscopy has been scarcely described, with a reported yield of 70.6%. OBJECTIVES: The aim of this study is to assess diagnostic yield for GGNs using shape-sensing robotic-assisted bronchoscopy (ssRAB). METHOD: A retrospective study of patients who underwent ssRAB for evaluation of GGNs, from September 2021 to April 2023. Primary outcome was diagnostic yield of ssRAB for GGNs, secondary outcomes were sensitivity for malignancy, and complications that required admission or intervention. RESULTS: A total of 23 nodules were biopsied from 22 patients. Median age was 71 years (IQR 66-81), 63.6% were female, and 40.9% had a previous history of cancer. Forty-three percent of nodules were in the right upper lobes, and the median lesion size was 1.8 × 1.21. Twelve were subsolid nodules (SSNs), and 11 were pure GGNs. Overall diagnostic yield was 87%, with a sensitivity for malignancy of 88.9%. Adenocarcinoma was the most common malignancy diagnosed (70%). No procedure-related complications were reported. CONCLUSION: The use of ssRAB shows a high diagnostic yield for diagnosing GGN and SSN with less than 6 mm solid component with a low risk for complications.

Management of Significant Airway Bleeding during Robotic Assisted Bronchoscopy: A Tailored Approach.

Robotic assisted bronchoscopy represents a major turning point in bronchoscopic history. The management strategies to address significant airway bleeding in this "robotic era" are not well documented, and further guidance is required. We present a case report that exemplifies our approach and management strategy using a combined and simultaneous flexible/robotic bronchoscopy if this complication is encountered.

Association between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Lung Cancer.

OBJECTIVES: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the most commonly prescribed antihypertensives, with prior studies identifying a possible association between long-term use and increased rates of lung cancer. This study evaluated this potential association in a large population using propensity matching. METHODS: This was a population-based cohort study in a large healthcare system in three regions of the United States. Pairwise propensity score matching was performed using demographics and comorbidities. All of the adult patients in the healthcare system from January 1, 2000 to April 30, 2018 with at least 1 year of follow-up were included. RESULTS: In total, 3,253,811 patients with a median age of 59 (range 18-103) years were included. The ACEI group had a higher freedom from lung cancer versus controls at 15 years (98.47%, 95% confidence interval [CI] 98.41-98.54) versus 98.26%, (95% CI 98.20-98.33), whereas ARBs had similar rates versus controls at all time points. For patients diagnosed as having lung cancer, median all-cause survival was significantly higher in the ACEI (34.7 months, 95% CI 32.8-36.6) and ARB (30.9 months, 95% CI 28.1-33.8) groups than the control group (20.6 months, 95% CI 20.1-21.1). CONCLUSIONS: This study showed lower rates of lung cancer with ACEI use and no difference in risk with ARBs. In addition, use of these medications was found to be associated with increased survival in those diagnosed as having lung cancer. This study supports the continued use of these medications without concern for increasing the risk of lung cancer.

A multi-state model of the CaMKII dodecamer suggests a role for calmodulin in maintenance of autophosphorylation.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) accounts for up to 2 percent of all brain protein and is essential to memory function. CaMKII activity is known to regulate dynamic shifts in the size and signaling strength of neuronal connections, a process known as synaptic plasticity. Increasingly, computational models are used to explore synaptic plasticity and the mechanisms regulating CaMKII activity. Conventional modeling approaches may exclude biophysical detail due to the impractical number of state combinations that arise when explicitly monitoring the conformational changes, ligand binding, and phosphorylation events that occur on each of the CaMKII holoenzyme's subunits. To manage the combinatorial explosion without necessitating bias or loss in biological accuracy, we use a specialized syntax in the software MCell to create a rule-based model of a twelve-subunit CaMKII holoenzyme. Here we validate the rule-based model against previous experimental measures of CaMKII activity and investigate molecular mechanisms of CaMKII regulation. Specifically, we explore how Ca2+/CaM-binding may both stabilize CaMKII subunit activation and regulate maintenance of CaMKII autophosphorylation. Noting that Ca2+/CaM and protein phosphatases bind CaMKII at nearby or overlapping sites, we compare model scenarios in which Ca2+/CaM and protein phosphatase do or do not structurally exclude each other's binding to CaMKII. Our results suggest a functional mechanism for the so-called "CaM trapping" phenomenon, wherein Ca2+/CaM may structurally exclude phosphatase binding and thereby prolong CaMKII autophosphorylation. We conclude that structural protection of autophosphorylated CaMKII by Ca2+/CaM may be an important mechanism for regulation of synaptic plasticity.

Endoscopic Lung Volume Reduction in Relation to Body Mass Index in Patients with Severe Heterogeneous Emphysema.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), body mass index (BMI) is significantly lower in the emphysema-dominant type. Endoscopic lung volume reduction (ELVR) is an innovative way of treating severe emphysema. However, the specific associations of low BMI values and outcomes of ELVR is not well-studied. OBJECTIVES: We evaluated associations between initial BMI and changes in major outcomes after endobronchial valve (EBV) placement in patients with heterogeneous severe emphysema. METHODS: In a retrospective cohort study, patients were divided into 2 groups based on their baseline BMI (higher BMI ≥21 kg/m2 [n = 18] and lower BMI <21 kg/m2 [n = 63]). Demographics, procedure data, pulmonary function test and 6-min-walk test (6MWT), dyspnea score (according to the modified Medical Research Council [mMRC] scale), BODE (BMI, airflow obstruction, dyspnea, exercise capacity) index, and complications were recorded. After 6 months, changes in variables (dWeight and dBMI) were recorded. RESULTS: Comparing the 2 groups, we found the following: a dWeight of -2.34 kg and +3.39 kg (p value <0.01) and a dBMI of -0.74 and +1.99 kg/m2, in the higher BMI and lower BMI group, respectively (p value <0.01). Changes in forced expiratory volume <1 s (FEV1), 6MWT, mMRC score, and BODE index were not statistically significant. The most common complication was pneumothorax. The lower BMI group experienced more complications than the higher BMI group (40 vs. 24%). CONCLUSION: Baseline BMI is relevant when selecting candidates for ELVR. Our results show that the COPD patients with a lower BMI gained a significant amount of weight, thus increasing their BMI after the procedure. The rate of complications was higher in the lower BMI group. These findings should alert physicians and encourage nutritional assessment in this population.

Efficacy of the Spiration Valve System in Patients with Severe Heterogeneous Emphysema: A Systematic Review and Meta-Analysis.

BACKGROUND: Spiration Valve System (SVS) is an alternative for patients with severe heterogeneous emphysema; however, data about efficacy from randomized controlled trials (RCT) are unclear. OBJECTIVES: To explore both efficacy and safety of SVS in patients with severe emphysema and hyperinflation. METHODS: We included PubMed, EMBASE, Coch-rane database. All searches were performed until August 2019. Only RCTs were included for analysis. Risk of bias was assessed using Cochrane risk of bias tool. A meta-analysis evaluated change in forced expiratory volume in 1 s (FEV1), 6-min walking test (6MWT), residual volume, modified medical research council (mMRC) and Saint George respiratory questionnaire (SGRQ), all-cause mortality, risk of pneumothorax, and risk of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Quality of the evidence was rated using GRADE approach. RESULTS: Four RCTs including 629 subjects were included. SVS showed an overall change of 0.03 L (-0.07 to 0.13, I2 = 90%) in the in FEV1 (L) and a 2.03% (-2.50 to 6.57, I2 = 96%) in the predicted FEV1 (%) compared to baseline; however, studies without collateral ventilation (CV) showed an improvement of 0.12 L (95% CI 0.09-0.015, I2 = 0%), This subgroup also reported better results in SGRQ -12.27 points (95% CI -15.84 to -8.70, I2 = 0%) and mMRC -0.54 (95% CI -0.74 to -0.33, I2 = 0%). We found no benefit in 6MWT mean difference = 4.56 m (95% CI -21.88 to 31.00, I2 = 73%). Relative risk of mortality was 2.54 (95% CI 0.81-7.96, I2 = 0%), for pneumothorax 3.3 (95% CI 0.61-18.12, I2 = 0%) and AECOPD 1.68 (95% CI 1.04-2.70, I2 = 0%). CONCLUSION: In patients with severe heterogeneous emphysema and hyperinflation without CV, SVS is an alternative that showed an improvement in pulmonary function, quality of life, and dyspnea score with an acceptable risk profile.

Competitive tuning: Competition's role in setting the frequency-dependence of Ca2+-dependent proteins.

A number of neurological disorders arise from perturbations in biochemical signaling and protein complex formation within neurons. Normally, proteins form networks that when activated produce persistent changes in a synapse's molecular composition. In hippocampal neurons, calcium ion (Ca2+) flux through N-methyl-D-aspartate (NMDA) receptors activates Ca2+/calmodulin signal transduction networks that either increase or decrease the strength of the neuronal synapse, phenomena known as long-term potentiation (LTP) or long-term depression (LTD), respectively. The calcium-sensor calmodulin (CaM) acts as a common activator of the networks responsible for both LTP and LTD. This is possible, in part, because CaM binding proteins are "tuned" to different Ca2+ flux signals by their unique binding and activation dynamics. Computational modeling is used to describe the binding and activation dynamics of Ca2+/CaM signal transduction and can be used to guide focused experimental studies. Although CaM binds over 100 proteins, practical limitations cause many models to include only one or two CaM-activated proteins. In this work, we view Ca2+/CaM as a limiting resource in the signal transduction pathway owing to its low abundance relative to its binding partners. With this view, we investigate the effect of competitive binding on the dynamics of CaM binding partner activation. Using an explicit model of Ca2+, CaM, and seven highly-expressed hippocampal CaM binding proteins, we find that competition for CaM binding serves as a tuning mechanism: the presence of competitors shifts and sharpens the Ca2+ frequency-dependence of CaM binding proteins. Notably, we find that simulated competition may be sufficient to recreate the in vivo frequency dependence of the CaM-dependent phosphatase calcineurin. Additionally, competition alone (without feedback mechanisms or spatial parameters) could replicate counter-intuitive experimental observations of decreased activation of Ca2+/CaM-dependent protein kinase II in knockout models of neurogranin. We conclude that competitive tuning could be an important dynamic process underlying synaptic plasticity.

Clinical Outcomes With Extracorporeal Membrane Oxygenation for Interstitial Lung Disease: Systematic Review and Meta-Analysis.

The evidence on indications, outcomes, and complications with the use of extracorporeal membrane oxygenation (ECMO) in the setting of interstitial lung disease (ILD) is limited in the existing literature. We performed a systematic review and meta-analysis for the use of ECMO in the setting of ILD to study the prognostic factors associated with in-hospital mortality. Eighteen unique studies with a total of 1,356 patients on ECMO for ILD were identified out of which 76.5% were on ECMO as a bridge to transplant (BTT) and the rest as a bridge to recovery (BTR). The overall in-hospital mortality was 45.76%, with 71.3% and 37.8% for BTR and BTT, respectively. Among the various prognostic factors, mortality was lower with younger age (mean difference = 3.15, 95% confidence interval [CI] = 0.82-5.49), use of awake veno-arterial (VA)-ECMO compared to veno-venous (VV)-ECMO (unadjusted odds ratio [OR] = 0.22, 95% CI = 0.13-0.37) in the overall cohort. In the setting of BTT, the use of VA-ECMO had a decreased hazard ratio (HR) compared to VV-ECMO (adjusted HR = 0.34, 95% CI = 0.15-0.81, p = 0.015). The findings of our meta-analysis are critical but are derived from retrospective studies with small sample sizes and thus are of low to very low-GRADE certainty.

Association of antibiotics with the outcomes in COVID-19 pneumonia patients with elevated PCT levels.

OBJECTIVE: To assess antibiotics impact on outcomes in COVID-19 pneumonia patients with varying procalcitonin (PCT) levels. METHODS: This retrospective cohort study included 3665 COVID-19 pneumonia patients hospitalized at five Mayo Clinic sites (March 2020 to June 2022). PCT levels were measured at admission. Patients' antibiotics use and outcomes were collected via the Society of Critical Care Medicine (SCCM) Viral Infection and Respiratory Illness Universal Study (VIRUS) registry. Patients were stratified into high and low PCT groups based on the first available PCT result. The distinction between high and low PCT was demarcated at both 0.25 ng/ml and 0.50 ng/ml. RESULTS: Our cohort consisted of 3665 patients admitted with COVID-19 pneumonia. The population was predominantly male, Caucasian and non-Hispanic. With the PCT cut-off of 0.25 ng/ml, 2375 (64.8 %) patients had a PCT level <0.25 ng/mL, and 1290 (35.2 %) had PCT ≥0.25 ng/ml. While when the PCT cut off of 0.50 ng/ml was used we observed 2934 (80.05 %) patients with a PCT <0.50 ng/ml while 731(19.94 %) patients had a PCT ≥0.50 ng/ml. Patients with higher PCT levels exhibited significantly higher rates of bacterial infections (0.25 ng/ml cut-off: 4.2 % vs 7.9 %; 0.50 ng/ml cut-off: 4.6 % vs 9.2 %). Antibiotics were used in 66.0 % of the cohort. Regardless of the PCT cutoffs, the antibiotics group showed increased hospital length of stay (LOS), intensive care unit (ICU) admission rate, and mortality. However, early de-escalation (<24 h) of antibiotics correlated with reduced hospital LOS, ICU LOS, and mortality. These results were consistent even after adjusting for confounders. CONCLUSION: Our study shows a substantial number of COVID-19 pneumonia patients received antibiotics despite a low incidence of bacterial infections. Therefore, antibiotics use in COVID pneumonia patients with PCT <0.5 in the absence of clinical evidence of bacterial infection has no beneficial effect.

Real-time visualization of lung malignancy with needle-based confocal laser endomicroscopy during shape-sensing robotic-assisted bronchoscopy.

Robotic-assisted bronchoscopy (RAB) improves endoscopic diagnostic yield of solitary pulmonary nodules (SPN). Needle-based confocal laser endomicroscopy (nCLE) is an emerging technology that allows high-resolution, in-vivo, real-time assessment of living tissues at a cellular and subcellular level. Their combined use has been scarcely reported. We used them simultaneously in three patients with SPNs. For each, the nodule was evaluated with nCLE and sampled for pathology, followed by mediastinal staging. Median age was 77 years (67% male). Median nodule minimum size was 1.8 cm and maximum was 2.1 cm. nCLE detected abnormal patterns suggestive of malignancy for all nodules and pathology confirmed primary lung adenocarcinomas in two patients and lung primary squamous cell carcinoma in the other. The combined use of RAB with nCLE may potentially enhance the differentiation of malignant cells in real-time and increase sample adequacy, accuracy, and diagnostic yield when biopsying a suspicious pulmonary lesion.

Automatic 4D Flow MRI Segmentation Using the Standardized Difference of Means Velocity.

We present a method to automatically segment 4D flow magnetic resonance imaging (MRI) by identifying net flow effects using the standardized difference of means (SDM) velocity. The SDM velocity quantifies the ratio between the net flow and observed flow pulsatility in each voxel. Vessel segmentation is performed using an F-test, identifying voxels with significantly higher SDM velocity values than background voxels. We compare the SDM segmentation algorithm against pseudo-complex difference (PCD) intensity segmentation of 4D flow measurements in in vitro cerebral aneurysm models and 10 in vitro Circle of Willis (CoW) datasets. We also compared the SDM algorithm to convolutional neural network (CNN) segmentation in 5 thoracic vasculature datasets. The in vitro flow phantom geometry is known, while the ground truth geometries for the CoW and thoracic aortas are derived from high-resolution time-of-flight (TOF) magnetic resonance angiography and manual segmentation, respectively. The SDM algorithm demonstrates greater robustness than PCD and CNN approaches and can be applied to 4D flow data from other vascular territories. The SDM to PCD comparison demonstrated an approximate 48% increase in sensitivity in vitro and 70% increase in the CoW, respectively; the SDM and CNN sensitivities were similar. The vessel surface derived from the SDM method was 46% closer to the in vitro surfaces and 72% closer to the in vitro TOF surfaces than the PCD approach. The SDM and CNN approaches both accurately identify vessel surfaces. The SDM algorithm is a repeatable segmentation method, enabling reliable computation of hemodynamic metrics associated with cardiovascular disease.

Real-time Quantification of in vivo cerebrospinal fluid velocity using fMRI inflow effect.

In vivo estimation of cerebrospinal fluid (CSF) velocity is crucial for understanding the glymphatic system and its potential role in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Current cardiac or respiratory gated approaches, such as 4D flow MRI, cannot capture CSF movement in real time due to limited temporal resolution and in addition deteriorate in accuracy at low fluid velocities. Other techniques like real-time PC-MRI or time-spatial labeling inversion pulse are not limited by temporal averaging but have limited availability even in research settings. This study aims to quantify the inflow effect of dynamic CSF motion on functional magnetic resonance imaging (fMRI) for in vivo, real-time measurement of CSF flow velocity. We considered linear and nonlinear models of velocity waveforms and empirically fit them to fMRI data from a controlled flow experiment. To assess the utility of this methodology in human data, CSF flow velocities were computed from fMRI data acquired in eight healthy volunteers. Breath holding regimens were used to amplify CSF flow oscillations. Our experimental flow study revealed that CSF velocity is nonlinearly related to inflow effect-mediated signal increase and well estimated using an extension of a previous nonlinear framework. Using this relationship, we recovered velocity from in vivo fMRI signal, demonstrating the potential of our approach for estimating CSF flow velocity in the human brain. This novel method could serve as an alternative approach to quantifying slow flow velocities in real time, such as CSF flow in the ventricular system, thereby providing valuable insights into the glymphatic system's function and its implications for neurological disorders.

Does COVID-19 impair V̇o2peak in patients with cardiorespiratory disease? Insight from cardiopulmonary responses to maximal exercise pre- and post-illness.

Reduced exercise capacity has been suggested as a cardinal sequela of COVID-19. However, only cross-sectional approaches that either do not consider individuals with concomitant cardiorespiratory disease or account for exercise capacity before infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) support this assumption. Is reduced exercise capacity a sequela of SARS-CoV-2 infection in patients with concomitant cardiorespiratory disease? We retrospectively reviewed cardiopulmonary exercise testing (CPET) data collected across three hospitals between October 2018 and March 2022. Forty-two patients who completed a CPET before and after COVID-19 and 25 patients who performed two separate CPETs but did not contract COVID-19 (CTL) were included. Within each patient, the same test protocol was performed at the first and second CPETs. The time between CPETs was similar between the groups (COVID-19 489 ± 534 vs. CTL 534 ± 257 days, P = 0.662). The COVID-19 group performed the CPETs 312 ± 232 days before and 176 ± 110 days after infection. Exercise time, peak heart rate, peak systolic pressure, oxygen uptake (V̇o2) at anaerobic threshold, peak ventilation, and ventilatory efficiency were not different between the CPETs in both groups. Peak V̇o2 was reduced from before to after SARS-CoV-2 infection. However, the change in V̇o2peak from the first to the second CPET was not different between COVID-19 vs. CTL. Accounting for V̇o2peak before COVID-19 and including a group of control patients, we find limited evidence for reduced exercise capacity as a sequela of SARS-CoV-2 infection in patients with concomitant cardiorespiratory disease.NEW & NOTEWORTHY There is accumulating evidence that reduced exercise capacity is, or can be, an outcome following COVID-19. However, evidence to date relies upon cross-sectional approaches that either do not consider patients with concomitant cardiorespiratory disease or account for pre-infection exercise capacity data. Accounting for V̇o2peak before COVID-19 and including a group of control patients, we find limited evidence for reduced exercise capacity as a sequela of SARS-CoV-2 infection in patients with concomitant cardiorespiratory disease.

Coordination of Care for Expiratory Central Airway Collapse: A Structured Process for a Multifaceted Disease.

Common respiratory symptoms, including dyspnea, cough, sputum production, and recurrent infections, frequently remain without a clear cause and may be the result of expiratory central airway collapse (ECAC). Establishing the diagnosis and appropriate treatment plan for patients with ECAC is challenging and benefits from a multidisciplinary approach. A coordinator role is crucial in this process to ensure optimal patient-centered outcomes. We describe the coordination of care in the process of diagnosing and treating ECAC. The coordinator leads the organization of the multiple services involved in the care of patients with ECAC, including pulmonary medicine, interventional pulmonology, radiology, and thoracic surgery, as well as hospital inpatient staff. From initial screening to evaluation and management with airway stents and corrective treatment with tracheobronchoplasty, the ECAC coordinator oversees the entire process of care for patients with ECAC.

Association of plasma volume status with outcomes in hospitalized Covid-19 ARDS patients: A retrospective multicenter observational study.

PURPOSE: To evaluate the association of estimated plasma volume (ePV) and plasma volume status (PVS) on admission with the outcomes in COVID-19-related acute respiratory distress syndrome (ARDS) patients. MATERIALS AND METHODS: We performed a retrospective multi-center study on COVID-19-related ARDS patients who were admitted to the Mayo Clinic Enterprise health system. Plasma volume was calculated using the formulae for ePV and PVS, and these variables were analyzed for correlation with patient outcomes. RESULTS: Our analysis included 1298 patients with sequential organ failure assessment (SOFA) respiratory score ≥ 2 (PaO2/FIO2 ≤300 mmHg) and a mortality rate of 25.96%. A Cox proportional multivariate analysis showed PVS but not ePV as an independent correlation with 90-day mortality after adjusting for the covariates (HR: 1.015, 95% CI: 1.005-1.025, p = 0.002 and HR 1.054, 95% CI 0.958-1.159, p = 0.278 respectively). CONCLUSION: A lower PVS on admission correlated with a greater chance of survival in COVID-19-related ARDS patients. The role of PVS in guiding fluid management should be investigated in future prospective studies.

Prevention of acute exacerbation of chronic obstructive pulmonary disease after bronchoscopic lung volume reduction with endobronchial valves.

INTRODUCTION: Bronchoscopic lung volume reduction (BLVR) with endobronchial valves (EBVs) has emerged as an important treatment method for patients with severe chronic obstructive pulmonary disease (COPD). Acute exacerbations of COPD (AECOPD) are a frequent complication following BLVR with EBV. However, there is no consensus on the prevention of AECOPD. OBJECTIVES: Our study aims to compare the outcomes of different prophylactic measures on the occurrence of AECOPD after BLVR with EBV. METHODS: We conducted a multicenter, retrospective study of patients who underwent BLVR with EBV at six different institutions. Emphasis was directed towards the specific practices aimed at preventing AECOPD: antibiotics, steroids, antibiotics plus steroids, or no prophylaxis. Subgroups were compared, and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. RESULTS: A total of 170 patients were reviewed. The rate of AECOPD was 21.2% for the full cohort. Patients who received prophylaxis had a significantly lower rate of AECOPD compared with those who did not (16.7% vs. 46.2%; p = 0.001). The rate was lowest in patients who received antibiotics alone (9.2%). There was no significant difference in the rate of AECOPD between patients who received steroids alone or antibiotics plus steroids, compared with the other subgroups. The OR for AECOPD was 4.3 (95% CI: 1.8-10.4; p = 0.001) for patients not receiving prophylaxis and 3.9 (95% CI: 1.5-10.1; p = 0.004) for prophylaxis other than antibiotics alone. CONCLUSIONS: Administration of antibiotics after BLVR with EBV was associated with a lower rate of AECOPD. This was not observed with the use of steroids or in combination with antibiotics.