Recommended assessment and management of sleep disordered breathing in patients with atrial fibrillation, hypertension and heart failure: Taiwan Society of Cardiology/Taiwan Society of sleep Medicine/Taiwan Society of pulmonary and Critical Care Medicine joint consensus statement.

Sleep disordered breathing (SDB) is highly prevalent and may be linked to cardiovascular disease in a bidirectional manner. The Taiwan Society of Cardiology, Taiwan Society of Sleep Medicine and Taiwan Society of Pulmonary and Critical Care Medicine established a task force of experts to evaluate the evidence regarding the assessment and management of SDB in patients with atrial fibrillation (AF), hypertension and heart failure with reduced ejection fraction (HFrEF). The GRADE process was used to assess the evidence associated with 15 formulated questions. The task force developed recommendations and determined strength (Strong, Weak) and direction (For, Against) based on the quality of evidence, balance of benefits and harms, patient values and preferences, and resource use. The resulting 11 recommendations are intended to guide clinicians in determining which the specific patient-care strategy should be utilized by clinicians based on the needs of individual patients.

Chest roentgenography is complementary to interferon-gamma release assay in latent tuberculosis infection screening of rheumatic patients.

BACKGROUND: A study of latent tuberculosis infection (LTBI) burden by chest roentgenography (CXR) with reference to interferon-gamma release assay (IGRA) is still lacking in rheumatic patients of an intermediate tuberculosis burden area. METHODS: We retrospectively reviewed clinical data of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) receiving LTBI screening for biologics from Jan 2013 to April 2014. RESULTS: A total of 238 rheumatic patients who underwent LTBI screening were included in this study, of whom 46 (19.3%) had positive IGRA tests, 178 (74.8%) had negative results, and 14 (5.9%) had indeterminate results. Radiological findings suggesting healed tuberculosis (CXR-old-TB) were found in 18.1% of all patients, 23.9% in the IGRA -positive patients vs 16.9% in the IGRA-negative patients (OR 1.55 95% CI: 0.71-3.39, p = 0.27). Forty (40/46, 87.0%) IGRA-positive patients received isoniazid prophylaxis and 77.5% of them finished treatment. Six patients developed adverse effects of isoniazid treatment, resulting in an overall number needed to harm (NNH) of 6.7 (40/6). IGRA-non-positive patients with old TB-suggestive CXR comprised 13.4% (32/238) of all our rheumatic patients, and one of them developed pulmonary tuberculosis within one year after screening. CONCLUSIONS: LTBI disease burden in rheumatic patients is substantial according to the estimation of CXR and IGRA screening. Correlation between CXR and IGRA is not significant in rheumatic patients, which implies their complementary roles. IGRA-non-positive patients with old TB-suggestive CXR comprise a significant portion in rheumatic patients and merit cautious follow-up by rheumatologists, tuberculosis specialists, and pulmonologists.

Obstructive sleep apnea and chronic kidney disease.

PURPOSE OF REVIEW: Obstructive sleep apnea (OSA) is highly prevalent in patients with chronic kidney disease (CKD). The relationship between OSA and CKD is likely to be bi-directional. On one hand, the presence of OSA leads to intermittent hypoxia, sympathetic nervous system activity, and hypertension, all of which may have deleterious effects on kidney function. On the other hand, in patients with end-stage renal disease (ESRD), intensification of renal replacement therapy has been shown to attenuate sleep apnea severity, suggesting that the renal disease itself contributes to the pathogenesis of OSA. The present review describes our current understanding of the bi-directional relationship between OSA and CKD. RECENT FINDINGS: Studies suggest that the presence of OSA and nocturnal hypoxia may lead to worsening of kidney function. One potential mechanism is activation of the renin-angiotensin system by OSA, an effect which may be attenuated by CPAP therapy. In ESRD, fluid overload plays an important role in the pathogenesis of OSA and fluid removal by ultrafiltration leads to marked improvements in sleep apnea severity. SUMMARY: OSA is associated with accelerated loss of kidney function. In patients with ESRD, fluid overload plays an important role in the pathogenesis of OSA.

Tuberculosis mortality: patient characteristics and causes.

BACKGROUND: In the antibiotic era, tuberculosis (TB) still causes a substantial number of mortalities. We aimed to identify the causes and risks of death among TB patients. METHODS: Medical records of mortality cases of culture-proven TB diagnosed during 2003-2007 were reviewed. All TB deaths were classified into 2 groups (TB-related and non-TB-related), based on the underlying cause of death. RESULTS: During the study period, 2016 cases (male: 71.1%) of culture-proven TB were identified. The mean age was 59.3 (range: 0.3-96) years. The overall mortality rate was 12.3% (249 cases) and the mean age at death was 74 years; 17.3% (43 cases) of all TB deaths were TB-related. Most of the TB-related deaths occurred early (median survival: 20 days), and the patient died of septic shock. Malignancy, liver cirrhosis, renal failure, and miliary and pneumonic radiographic patterns were all independent predictors for all TB deaths. Cavitary, miliary and pneumonic radiographic patterns were all significant predictive factors for TB-related death. Extrapulmonary involvement and liver cirrhosis were also factors contributing to TB-related death. CONCLUSIONS: The majority of TB deaths were ascribed to non-TB-related causes. Managing TB as well as underlying comorbidities in a multidisciplinary approach is essential to improve the outcome of patients in an aging population. However, the clinical manifestations of patients with TB-related death vary; many progressed to fulminant septic shock requiring timely recognition with prompt treatment to prevent early death.

Sex-based differences in obstructive sleep apnea and atrial fibrillation: Implication of atrial fibrillation burden.

Background: Obstructive sleep apnea (OSA) is a risk factor for atrial fibrillation (AF); however, it is unclear whether AF increases the risk of OSA. Furthermore, sex differences among patients with both AF and OSA remain unclear. We aimed to determine the association between an increased AF burden and OSA and investigate the differences in clinical characteristics between women and men with AF and OSA. Methods: This was a descriptive, cross-sectional analysis from a prospective cohort study. Patients with non-valvular AF were recruited from the cardiac electrophysiology clinic of a tertiary center; they underwent a home sleep apnea test and 14-day ambulatory electrocardiography. Moderate-to-severe OSA was defined as an apnea-hypopnea index of ≥15. Results: Of 320 patients with AF, 53.4% had moderate-to-severe OSA, and the mean body mass index (BMI) was 25.6 kg/m2. Less women (38.2%) had moderate-to-severe OSA than men (59.3%) (p < 0.001). In the multivariate analysis, age, being a man, and BMI were significantly associated with moderate-to-severe OSA. AF burden was associated with moderate-to-severe OSA only in men (odds ratio: 1.008; 95% confidence interval: 1.001-1.014). Women and men with OSA had similar BMI (p = 0.526) and OSA severity (p = 0.754), but women were older than men (70.1 ± 1.3 vs. 63.1 ± 0.9 years, p < 0.001). Women with moderate-to-severe OSA had a lower AF burden than men did (27.6 ± 7.1 vs. 49.5 ± 3.9%, p = 0.009). Conclusions: AF burden is a sex-specific risk factor for OSA and is limited to men. In contrast, women with both AF and OSA have a lower AF burden than men, despite being older and having similar OSA severity and body habitus. Thus, AF may develop later in women with OSA than in men.

Obstructive sleep apnea and nocturnal attacks of paroxysmal atrial fibrillation.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is commonly seen in patients with atrial fibrillation (AF), but it is unclear to what extent this relationship is one of causation or association. We examined a cohort of patients with paroxysmal AF to determine whether the presence of OSA (apnea-hypopnea index ≥ 15 events/h) affects the time of onset of symptomatic AF episodes. METHODS: Patients with a recent emergency department visit for a symptomatic episode of paroxysmal AF were recruited from an AF clinic. The time of onset of the AF attack was classified as occurring in "sleeping hours" or "waking hours" based on direct history from the patient and emergency department visit documentation. RESULTS: Of 152 patients with paroxysmal AF, 67 underwent polysomnography; 1 (1.5%) had central sleep apnea, 46 (68.7%) had mild or no OSA, and 20 (29.8%) had OSA. In the OSA group, 14/20 (70.0%) had their symptomatic AF attack during sleeping hours compared to 12/46 (26.1%) in the mild or no OSA group (P = .001). Compared with those who had a paroxysmal AF attack during waking hours, and adjusting for confounders, those who had a paroxysmal AF attack during sleeping hours had almost 6 times the odds of having OSA (odds ratio, 5.53; P = .007). CONCLUSIONS: Compared to patients with paroxysmal AF with mild or no OSA, those with OSA were far more likely to have a symptomatic AF attack during sleeping hours, supporting a causal role for OSA in the pathogenesis of AF in this population. These findings strongly suggest that patients who have nocturnal AF attacks should be evaluated for OSA. CITATION: Lin C-H, Timofeeva M, O'Brien T, Lyons OD. Obstructive sleep apnea and nocturnal attacks of paroxysmal atrial fibrillation. J Clin Sleep Med. 2022;18(5):1279-1286.

Soluble triggering receptor expressed on myeloid cells-1 as an infection marker for patients with neutropenic fever.

OBJECTIVE: To assess the value of soluble triggering receptor expressed on myeloid cells-1 as a biomarker of infection in patients with neutropenic fever comparing with procalcitonin and C-reactive protein. DESIGN: Prospective, comparative, single-center study. SETTING: Hematology ward at a university hospital. SUBJECTS: Seventy-five patients with neutropenic fever after chemotherapy for their hematologic malignancies. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: A total of 137 episodes of neutropenic fever in 75 patients were classified into 75 episodes of documented infections and 62 low likelihood of infection. The level of soluble triggering receptor expressed on myeloid cells-1 was significantly elevated in the group of documented infection. The area under the receiver operating characteristic curve for the diagnosis of infection was 0.719 (95% confidence interval, 0.632-0.806; p < .0001) for soluble triggering receptor expressed on myeloid cells-1, which was larger than the values of 0.501 for procalcitonin (0.465-0.657; p = .218) and 0.491 for C-reactive protein (0.394-0.589, p = .858). The fitted marginal logistic regression model of all episodes contained two statistically significant predictors of infection: soluble triggering receptor expressed on myeloid cells-1 (per 1-pg/mL increase; odds ratio [OR], 1.0002; 95% CI, 1.0001-1.0003; p < .0001) and procalcitonin (per 1-ng/mL increase; OR, 1.0094; 95% CI, 1.0005-1.0184; p = .0002). In a diagnostic panel with soluble triggering receptor expressed on myeloid cells-1 and procalcitonin, the sensitivity and specificity were 88% and 48%, respectively. CONCLUSIONS: Soluble triggering receptor expressed on myeloid cells-1 is better than procalcitonin in the prediction of infection at the onset of neutropenic fever. By applying soluble triggering receptor expressed on myeloid cells-1 and procalcitonin together, low or high risk for infection can be defined at the onset of neutropenic fever.

Sleep Apnea and Chronic Kidney Disease: A State-of-the-Art Review.

Patients with chronic kidney disease have increased morbidity and mortality, mainly due to cardiovascular disease. Compared with the general population, patients with chronic kidney disease have an increased prevalence of both OSA and central sleep apnea, and the presence of sleep apnea in this population has been associated with an increased risk of cardiovascular events and mortality. Although OSA can lead to an increase in the rate of kidney function decline, there is also evidence that the presence of end-stage renal disease can lead to worsening of sleep apnea, indicating a bidirectional relation between sleep apnea and chronic kidney disease. The objective of this review was to describe the epidemiology of sleep apnea in chronic kidney disease, understand the pathophysiological mechanisms by which OSA can lead to progression of chronic kidney disease, and consider the role of treatment with CPAP in this regard. The review also explores the pathophysiological mechanism by which end-stage renal disease can lead to sleep apnea and considers how intensification of renal replacement therapy or extra fluid removal by ultrafiltration may attenuate the degree of sleep apnea severity in this population.

Prospective Evaluation of Procalcitonin, Soluble Triggering Receptor Expressed on Myeloid Cells-1 and C-Reactive Protein in Febrile Patients with Autoimmune Diseases.

BACKGROUND: Both procalcitonin (PCT) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) have been investigated separately as indicators of infection in patients with autoimmune diseases. Our study simultaneously evaluated both PCT and sTREM-1 along with C-reactive protein (CRP) in febrile patients with autoimmune diseases. METHODS: Fifty-nine patients were enrolled in the study. The patients were categorized into the infection group (n=24) or the disease flare group (n=35). sTREM-1, PCT and CRP concentrations at fever onset were compared between the two groups of patients. RESULTS: sTREM-1 and CRP did not differ between the two groups. PCT [median (range), ng/ml] was higher in the infection group than in the disease flare group [0.53 (0.02-12.85) vs. 0.12 (0.02-19.23), p=0.001]. The area under the receiver-operating characteristic (ROC) for diagnosis of infection was 0.75 for PCT (p=0.001), 0.63 for CRP (p=0.09) and 0.52 for sTREM-1 (p=0.79). Using 0.2 ng/ml as the cutoff value for PCT, sensitivity was 0.75 and specificity was 0.77. Negative predictive values for PCT were 92%, 87% and 82% for a prevalence of infection of 20%, 30%, and 40%, respectively. Neither immunosuppressants nor biomodulators affected the level of the three biomarkers. However, in patients treated with corticosteroids, the levels of sTREM-1 and CRP were significantly decreased compared with the untreated patients. CONCLUSIONS: Setting PCT at a lower cutoff value could provide useful information on excluding infection in febrile patients with autoimmune diseases. The possible effect of corticosteroids on the level of sTREM-1 as an infection marker deserves further study.

The trend and the disease prediction of vascular endothelial growth factor and placenta growth factor in nontuberculous mycobacterial lung disease.

Nontuberculous mycobacteria (NTM)-lung disease (LD) is an increasing health problem worldwide. The diagnosis of this disease remains difficult, however the application of placenta growth factor (PlGF) and vascular endothelial growth factor (VEGF) has not yet been studied. We screened patients with Mycobacterium avium complex or M. abscessus isolated from sputum, and enrolled 32 patients with NTM-LD and 93 with NTM pulmonary colonization. The NTM-LD group had a lower body mass index, higher proportion of bronchiectasis, more respiratory symptoms and pulmonary lesions, and higher titers of sputum acid-fast stain than the NTM pulmonary colonization group. The plasma level of PlGF was lower in the NTM-LD group than in the NTM colonization group, whereas the level of VEGF was higher in the NTM-LD group. In multivariable logistic regression analysis excluding NTM cultures, the predictive model for NTM-LD included sputum AFS titer, a nodular-bronchiectasis radiographic pattern, plasma VEGF/PlGF ratio, and chest radiographic score (VEGF/P1GF ratio became not significant as a factor in multivariable generalized linear model). The four-factor predictive index had good positive likelihood ratio and negative likelihood ratio for predicting NTM-LD in the patients with NTM in their sputum.

Afatinib combined with cetuximab for lung adenocarcinoma with leptomeningeal carcinomatosis.

We report a patient with non-small cell lung cancer (NSCLC) developed leptomeningeal carcinomatosis (LMC) after 4 years of multiple treatments. High-dose tyrosine kinase inhibitor (TKI) was given for LMC at first but was not effective. She then received dual therapy combining of afatinib and cetuximab. Brain magnetic resonance imaging (MRI) showed a partial response of disease and the patient experienced a clinical benefit. Our case suggests that dual targeting of epidermal growth factor receptor (EGFR) by a combination of afatinib and cetuximab can be a potential novel treatment option in treating LMC when high-dose TKI failed.