Central sleep apnea: emphasizing recognition and differentiation.

INTRODUCTION: Central sleep apnea (CSA) is a sleep-related breathing disorder in which the effort to breathe is intermittently diminished or absent. CSA is a common disorder among patients with different cardiovascular disorders, including heart failure. In addition, a growing number of medications have been shown to induce CSA and CSA can emerge after initiation of treatment for obstructive sleep apnea. Accumulating evidence shows that CSA is a heterogeneous disorder with individual differences in clinical and biological characteristics and/or underlying pathophysiological mechanisms. AREAS COVERED: This narrative review offers an overview of the diagnostic aspects and classification of CSA, with an emphasis on heart failure patients, patients with CSA due to a medication and treatment-emergent CSA. The importance of evaluation of prognostic biomarkers in patients with different types of CSA is discussed. This narrative review synthesizes literature on CSA sourced from the PubMed database up to February 2024. EXPERT OPINION: CSA presents a remarkably diverse disorder, with treatment modalities exhibiting potentially varied efficacy across its various phenotypes. This highlights the imperative for tailored management strategies that are rooted in phenotype classification.

Subclinical epileptiform activity and sleep disturbances in Alzheimer's disease.

INTRODUCTION: Subclinical epileptiform activity (SEA) and sleep disturbances are frequent in Alzheimer's disease (AD). Both have an important relation to cognition and potential therapeutic implications. We aimed to study a possible relationship between SEA and sleep disturbances in AD. METHODS: In this cross-sectional study, we performed a 24-h ambulatory EEG and polysomnography in 48 AD patients without diagnosis of epilepsy and 34 control subjects. RESULTS: SEA, mainly detected in frontotemporal brain regions during N2 with a median of three spikes/night [IQR1-17], was three times more prevalent in AD. AD patients had lower sleep efficacy, longer wake after sleep onset, more awakenings, more N1%, less REM sleep and a higher apnea-hypopnea index (AHI) and oxygen desaturation index (ODI). Sleep was not different between AD subgroup with SEA (AD-Epi+) and without SEA (AD-Epi-); however, compared to controls, REM% was decreased and AHI and ODI were increased in the AD-Epi+ subgroup. DISCUSSION: Decreased REM sleep and more severe sleep-disordered breathing might be related to SEA in AD. These results could have diagnostic and therapeutic implications and warrant further study at the intersection between sleep and epileptiform activity in AD.

Catathrenia in severe obstructive sleep apnea: A novel entity never described before.

STUDY OBJECTIVES: Catathrenia, derived from the Greek κατά (kata) meaning below and θρηνώ (threnia) to lament, is characterized by expiratory groaning episodes during sleep. In a case series of nine patients with severe obstructive sleep apnea, we observed a peculiar groaning entity that has not been described before. METHODS: We described and illustrated the cases with polysomnographic tracings and additional audio recordings. RESULTS: All patients were men, obese (body mass index 39 ± 6 kg/m2) with an apnea-hypopnea index ranging from 47 to 125/h. In addition, we identified groaning events that were consistently preceded by a cortical arousal associated with a "rescue" respiration after an obstructive hypopnea or apnea. These events exhibited characteristics of "mixed apnea's", but the "central apnea-like part" was a prolonged expiratory groaning phase, with immediately after the terminal expiratory snort appearance of an obstructive apnea. In case the duration of this expiration was at least 10 s we calculated these events separately and the index was 8.4 ± 7.7/h. More rarely (index 0.6 ± 0.5/h) a "central apnea mimicking event" with groaning not followed by an obstruction, was observed. We also observed groaning episodes during expiration with a shorter duration (less than 10 s), not calculated separately. Positive airway pressure, which was well tolerated, eliminated these events. CONCLUSIONS: This novel catathrenia entity preceded by a cortical arousal and "rescue" respiration in response to obstructive events is intriguing. Possible explanations for these observations are further discussed in this article.

Recovery from shift work.

One fifth of today's workforce is engaged in shift work and exposed to various mental and physical health risks including shift work disorder. Efficiently recovering from shift work through physical and mental interventions allows us to mitigate negative effects on health, enables a better work-life balance and enhances our overall wellbeing. The aim of this review is to provide a state-of-the-art overview of the available literature. The role of sleep timing and naps, light therapy and psychotherapy, diet and exercise in recovery from shift work is presented here. We further review the impact of shift schedules and social support on post-shift unwinding.

Ultrasonographic Presentation and Anatomic Distribution of Lung Involvement in Patients with Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic auto-immune disease, typically affecting the joints, which can also present with lung involvement (pleuritis, interstitial lung disease, pulmonary nodules, etc.). Lung ultrasound (LUS) is an upcoming tool in the detection of these pulmonary manifestations. METHODS: We performed a 72-window LUS in 75 patients presenting to the outpatient rheumatology clinic and describe the abnormalities (presence of B-lines (vertical comet-tail artefacts), pleural abnormalities, pleural effusions, and subpleural nodules) on lung ultrasound. We created a topological mapping of the number of B-lines per intercostal zone. RESULTS: We observed pleural effusions, pleural abnormalities, and pleural nodules in, respectively, 1.3%, 45.3%, and 14% of patients. There were 35 (46.7%) patients who had less than 5 B-lines, 15 (20%) patients who had between 5 and 10 B-lines, 11 (14.6%) between 10 and 20, 10 (13.3%) between 20 and 50, 1 (1.3%) between 50 and 100, and 3 (4%) of patients who had more than 100 B-lines. CONCLUSIONS: LUS in patients with RA shows an array of abnormalities ranging from interstitial syndromes to pleural abnormalities, subpleural nodules, and pleural effusions. Hotspots for the presence of B-lines are situated bilaterally in the posterior subscapular regions, as well as the anterior right mid-clavicular region.

Insights into the Use of Point-of-Care Ultrasound for Diagnosing Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a sleeping disorder caused by complete or partial disturbance of breathing during the night. Existing screening methods include questionnaire-based evaluations which are time-consuming, vary in specificity, and are not globally adopted. Point-of-care ultrasound (PoCUS), on the other hand, is a painless, inexpensive, portable, and useful tool that has already been introduced for the evaluation of upper airways by anesthetists. PoCUS could also serve as a potential screening tool for the diagnosis of OSA by measuring different airway parameters, including retropalatal pharynx transverse diameter, tongue base thickness, distance between lingual arteries, lateral parapharyngeal wall thickness, palatine tonsil volume, and some non-airway parameters like carotid intima-media thickness, mesenteric fat thickness, and diaphragm characteristics. This study reviewed previously reported studies to highlight the importance of PoCUS as a potential screening tool for OSA.

In search of a cut-off apnea-hypopnea index in type 3 home portable monitors to diagnose and treat obstructive sleep apnea: a mathematical simulation.

The American Academy of Sleep Medicine (AASM) uses similar apnea-hypopnea index (AHI) cut-off values to diagnose and define severity of sleep apnea independent of the technique used: in-hospital polysomnography (PSG) or type 3 portable monitoring (PM). Taking into account that PM theoretically might underestimate the AHI, we explored whether a lower cut-off would be more appropriate. We performed mathematical re-calculations on the diagnostic PSG-AHI (scored using AASM 1999 rules) of 865 consecutive patients with an AHI of ≥20 events/h who started continuous positive airway pressure (CPAP). For a PSG-AHI of ≥15 events/h re-scored using AASM 2012 rules (PSG-AHIAASM2012 ), a PM-respiratory event index (REI)AASM2012 cut-off point of ≥15 events/h resulted in a post-test probability of 100% of having the disease, but with negative tests in 57.1%. A PM-REIAASM2012 cut-off of 8 events/h, still resulted in a positive post-test probability of 100% but with negative tests in only 34.3%. Combination of the cut-off values with clinical estimation of being 'at high risk' based on Epworth Sleepiness Scale (ESS) and Berlin Questionnaire scores only resulted in a small reduction in the percentage of negative tests (respectively 52.7% and 32.7%). After 6 months, CPAP adherence was not lower using the PM-REIAASM 2012 cut-off ≥8 events/h in comparison to ≥15 events/h (median 5.7 vs. 5.8 h/night, p = 0.368) and the reduction in ESS was similar too (median -4 and -5 points, p = 0.083). Consequently, using a lower PM-REIAASM2012 cut-off could result in cost savings because of less negative studies and lesser need for a confirmatory PSG or a performance of a CPAP trial.

Bronchoalveolar Lavage Fluid-Isolated Biomarkers for the Diagnostic and Prognostic Assessment of Lung Cancer.

Lung cancer is considered one of the most fatal malignant neoplasms because of its late detection. Detecting molecular markers in samples from routine bronchoscopy, including many liquid-based cytology procedures, such as bronchoalveolar lavage fluid (BALF), could serve as a favorable technique to enhance the efficiency of a lung cancer diagnosis. BALF analysis is a promising approach to evaluating the tumor progression microenvironment. BALF's cellular and non-cellular components dictate the inflammatory response in a cancer-proliferating microenvironment. Furthermore, it is an essential material for detecting clinically significant predictive and prognostic biomarkers that may aid in guiding treatment choices and evaluating therapy-induced toxicities in lung cancer. In the present article, we have reviewed recent literature about the utility of BALF analysis for detecting markers in different stages of tumor cell metabolism, employing either specific biomarker assays or broader omics approaches.

Lung Aeration in COVID-19 Pneumonia by Ultrasonography and Computed Tomography.

We conducted a prospective single-center observational study to determine lung ultrasound reliability in assessing global lung aeration in 38 hospitalized patients with non-critical COVID-19. On admission, fixed chest CT scans using visual (CTv) and software-based (CTs) analyses along with lung ultrasound imaging protocols and scoring systems were applied. The primary endpoint was the correlation between global chest CTs score and global lung ultrasound score. The secondary endpoint was the association between radiographic features and clinical disease classification or laboratory indices of inflammation. Bland−Altman analysis between chest CT scores obtained visually (CTv) or using software (CTs) indicated that only 1 of the 38 paired measures was outside the 95% limits of agreement (−4 to +4 score). Global lung ultrasound score was highly and positively correlated with global software-based CTs score (r = 0.74, CI = 0.55−0.86; p < 0.0001). Significantly higher median CTs score (p = 0.01) and lung ultrasound score (p = 0.02) were found in severe compared to moderate COVID-19. Furthermore, we identified significantly lower (p < 0.05) lung ultrasound and CTs scores in those patients with a more severe clinical condition manifested by SpO2 < 92% and C-reactive protein > 58 mg/L. We concluded that lung ultrasound is a reliable bedside clinical tool to assess global lung aeration in hospitalized non-critical care patients with COVID-19 pneumonia.

The Use of a Novel Quantitative Marker of Echogenicity of Pleural Fluid in Parapneumonic Pleural Effusions.

Background: Thoracic ultrasound is an essential tool in the daily clinical care of pleural effusions and especially parapneumonic pleural effusions (PPEs), in terms of diagnosis, management, and follow-up. Hypoechogenicity index (HI) is a quantitative marker of pleural fluid echogenicity. We aimed to examine associations of HI with pleural inflammation in patients with PPE. Methods: All patients included underwent a thoracic ultrasound with HI determination at the first day of their admission for a PPE. Thoracentesis was performed in all patients. Demographics, laboratory measurements, and clinical data were collected prospectively and recorded in all subjects. Results: Twenty-four patients with PPE were included in the study. HI was statistically significantly correlated with intensity of inflammation as suggested by pleural fluid LDH (p < 0.001, r = -0.831), pleural fluid glucose (p=0.022, r = 0.474), and pleural fluid pH (p < 0.001, r = 0.811). HI was correlated with ADA levels (p=0.005, r = -0.552). We observed a statistically significant correlation of HI with pleural fluid total cell number (p < 0.001, r = -0.657) and polymorphonuclears percentage (p=0.02, r = -0.590), as well as days to afebrile (p=0.046, r = -0.411), duration of chest tube placement (p < 0.001, r = -0.806), and days of hospitalization (p=0.013, r = -0.501). Discussion. HI presents a fast, easily applicable, objective, and quantitative marker of pleural inflammation that reliably reflects the intensity of pleural inflammation and could potentially guide therapeutic management of PPE.

Sarcoidosis-Like Reactions Induced by Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) are a newly developed component of cancer care that expands the treatment possibilities for patients. Their use has been associated with several immune-related adverse events, including ICI-induced sarcoidosis-like reactions. This article reviews the data concerning ICI-induced sarcoidosis-like reactions currently available in the medical literature. These reactions have been reported in three classes of ICIs: anti-cytotoxic T-lymphocyte associated protein 4 antibodies, programmed death 1 inhibitors and programmed death ligand 1 inhibitors. These reactions are indistinguishable from sarcoidosis with a similar histology, pattern of organ involvement, and pattern of clinical manifestations. The most common locations to observe granulomatous inflammation from these reactions is in intrathoracic locations (the lung and/or mediastinal lymph nodes) and the skin. The median time between initiation of an ICI and the development of a sarcoidosis-like reaction averaged 14 weeks. Clinicians have opted to use corticosteroids and/or discontinue the ICI, or take no action when these reactions have developed. Regardless of whether the clinician performed an intervention or not, these reactions have uniformly improved or resolved after ICI-treatment, which provides additional temporal evidence supporting the presence of a sarcoidosis-like reaction as opposed to sarcoidosis. There is even evidence that the development of an ICI-induced sarcoidosis-like reaction suggests that the ICI is effective as an anti-tumor agent and should be continued. As is the case for sarcoidosis, sarcoidosis-like reactions do not mandate antisarcoidosis therapy, especially if the condition is asymptomatic. When treatment of sarcoidosis-like reaction is required, it may be prudent to continue ICI therapy and add antisarcoidosis therapy because standard antisarcoidosis regimens seem to be effective. Further research into the mechanisms involved in the development of ICI-induced sarcoidosis-like reactions may give insights into the immunopathogenesis of sarcoidosis.

25-hydroxyvitamin D in malignant pleural disease: a prospective cohort study.

INTRODUCTION: Growing evidence suggests a role of vitamin D in various cancers but the significance of vitamin D in malignant pleural disease remains unexplored. We sought to investigate the concentration and diagnostic role of 25-hydroxyvitamin D (25(OH)D) in malignant pleural effusions. MATERIALS AND METHODS: Prospective study of consecutive treatment-naïve patients with a new diagnosis of pleural effusion. RESULTS: Seventy-eight patients were studied, 45 of whom had malignant pleural effusions. Concentration of 25(OH)D in pleural fluid was significantly higher than serum in both malignant (15.2 ng/mL (9.7, 25.6) versus 10.2 ng/mL (6.4, 17.7), P < .001) and benign (11.4 ng/mL (8.4, 23.6) versus 7.9 (5.9, 16.1), P < .001) pleural disease. Pleural fluid 25(OH)D was almost significantly higher in exudates compared to transudates (P = .050) but it did not differ significantly between malignant and benign effusions (P = .217) and it was not diagnostic for malignant pleural disease (area under the ROC curve .58, 95% CI .45-.71). CONCLUSIONS: In subjects with unselected pleural effusions, 25(OH)D in pleural fluid was not diagnostic for malignant pleural disease. The novel finding of convincingly and consistently higher 25(OH)D in pleural fluid than serum suggests a role for vitamin D in pleural disease and merits further research.

18F-FDG PET/CT Imaging of Pulmonary Mucinous Cystadenocarcinoma with Signet Ring Cells.

A 63-year-old male with a recently diagnosed right lung lesion was referred for staging. F-FDG PET/CT scan revealed a hypodense, cystic-like mass in the right upper lung lobe, which demonstrated low, diffuse 18F-FDG uptake, likely due to the presence of mucus, as well as intensely hypermetabolic right hilar and right paratracheal lymph nodes. Transbronchial biopsy revealed a primary pulmonary mucinous cystadenocarcinoma with the presence of signet ring cell carcinoma, a co-existence of two rare variants of lung adenocarcinoma. This case report demonstrates the metabolic phenotype along with the radiographic characteristics of this rare tumor and its metastases.

Correlation of pleural effusions' grayscale sonographic parameters with fluid's analysis results.

BACKGROUND: Quantitative sonographic methods are used to assess pleural fluid's volume but no validated method exists for the measurement of the fluids' density and other qualitative values. We suggest a quantitative method, based on the pixel density of the pleural effusion's image, in order to evaluate the echogenicity of pleural effusion. METHODS: Pleural ultrasound (US) was performed in 62 patients with pleural effusion. Five consequent images of the pleural effusion were retrieved through axial view between the 9th and the 10th rib and one from the 10th rib through coronal view and converted into the high-resolution tagged image file format. The mean echo levels of all pixels of the pleural effusion and of the 10th rib were counted, and the hypoechogenicity index (HI) was calculated according to the following formula: HI = mean echo level of all pixels of the rib/mean echo levels of all pixels of pleural effusion. HI greater than 1 indicates pleural effusion's hypoechogenicity. Diagnostic thoracocentesis was performed and biochemical markers were measured. RESULTS: LDH, Cell Count, pH and Effusion Pixels (Mean) were both significantly correlated and associated with pixel ratio. Conversely, pixel ratio was not correlated with any other ultrasonography-derived parameter or biomarker. CONCLUSIONS: This study introduced HI as new index, which could demonstrate the inflammation density of pleural effusions. Moreover, when used in combination with classical biomarkers, HI might be a useful adjunct for the discrimination of pleural transudate.

Biomarkers in sarcoidosis.

INTRODUCTION: Numerous biomarkers have been evaluated for the diagnosis, assessment of disease activity, prognosis, and response to treatment in sarcoidosis. In this report, we discuss the clinical and research utility of several biomarkers used to evaluate sarcoidosis. Areas covered: The sarcoidosis biomarkers discussed include serologic tests, imaging studies, identification of inflammatory cells and genetic analyses. Literature was obtained from medical databases including PubMed and Web of Science. Expert commentary: Most of the biomarkers examined in sarcoidosis are not adequately specific or sensitive to be used in isolation to make clinical decisions. However, several sarcoidosis biomarkers have an important role in the clinical management of sarcoidosis when they are coupled with clinical data including the results of other biomarkers.

Reticuloendothelial system involvement in untreated sarcoidosis patients as assessed by 18F-FDG PET scanning.

Not available.

Correlation of spleen metabolism assessed by 18F-FDG PET with serum interleukin-2 receptor levels and other biomarkers in patients with untreated sarcoidosis.

BACKGROUND: The objective of our study was to assess the possible relationship between splenic F-18-fluorodeoxyglucose (18F-FDG) uptake and other established biochemical markers of sarcoidosis activity. PATIENTS AND METHODS: Thirty treatment-naive sarcoidosis patients were prospectively enrolled in this study. They underwent biochemical laboratory tests, including serum interleukin-2 receptor (sIL-2R), serum C-reactive protein, serum angiotensin-I converting enzyme, and 24-h urine calcium levels, and a whole-body combined 18F-FDG PET/computed tomography (PET/CT) scan as a part of an ongoing study at our institute. These biomarkers were statistically compared in these patients. RESULTS: A statistically significant linear dependence was detected between sIL-2R and log-transformed spleen-average standard uptake value (SUV avg) (R2=0.488, P<0.0001) and log-transformed spleen-maximum standard uptake value (SUV max) (R2=0.490, P<0.0001). sIL-2R levels and splenic size correlated linearly (Pearson's r=0.373, P=0.042). Multivariate linear regression analysis revealed that this correlation remained significant after age and sex adjustment (ß=0.001, SE=0.001, P=0.024). No statistically significant associations were detected between (a) any two serum biomarkers or (b) between spleen-SUV measurements and any serum biomarker other than sIL-2R. CONCLUSION: Our analysis revealed an association between sIL-2R levels and spleen 18F-FDG uptake and size, whereas all other serum biomarkers were not significantly associated with each other or with PET 18F-FDG uptake. Our results suggest that splenic inflammation may be related to the systemic inflammatory response in sarcoidosis that may be associated with elevated sIL-2R levels.